{"id":"adalimumab","rwe":[{"pmid":"41903081","year":"2026","title":"Efficacy/Effectiveness, Safety and Treatment Persistence of Filgotinib in Rheumatoid Arthritis: A Narrative Review of Clinical Trials and Real-World Evidence.","finding":"","journal":"Rheumatology and therapy","studyType":"Clinical Study"},{"pmid":"41902472","year":"2026","title":"Personalised treatment in biologically naive patients with Crohn's disease: a systematic review of the last 10 years.","finding":"","journal":"Scandinavian journal of gastroenterology","studyType":"Clinical Study"},{"pmid":"41901264","year":"2026","title":"Advanced Medical Therapies for Perianal Fistulizing Crohn's Disease: A Systematic Review of Clinical, Radiological, Surgical, and Composite Outcomes.","finding":"","journal":"Pharmaceuticals (Basel, Switzerland)","studyType":"Clinical Study"},{"pmid":"41898347","year":"2026","title":"Tattoo-Associated Sarcoid-like Uveitis: A Multicenter Registry Study.","finding":"","journal":"Biomedicines","studyType":"Clinical Study"},{"pmid":"41898295","year":"2026","title":"MEWDS-like Presentation Unmasking Sequential Bilateral Multifocal Choroiditis: Insights from Longitudinal Multimodal Imaging.","finding":"","journal":"Biomedicines","studyType":"Clinical Study"}],"_fda":{"id":"08dbaffe-9d05-43cf-b24b-b44ade8685fc","set_id":"08dbaffe-9d05-43cf-b24b-b44ade8685fc","openfda":{"rxcui":["797544","2699315","2699319"],"spl_id":["08dbaffe-9d05-43cf-b24b-b44ade8685fc"],"brand_name":["IDACIO"],"spl_set_id":["08dbaffe-9d05-43cf-b24b-b44ade8685fc"],"package_ndc":["65219-558-08","65219-562-01","65219-332-95"],"product_ndc":["65219-558"],"generic_name":["ADALIMUMAB-AACF"],"product_type":["HUMAN PRESCRIPTION DRUG"],"manufacturer_name":["Fresenius Kabi USA, LLC"],"application_number":["BLA761255"],"is_original_packager":[true]},"version":"1","pregnancy":["8.1 Pregnancy Risk Summary Available studies with use of adalimumab during pregnancy do not reliably establish an association between adalimumab and major birth defects. Clinical data are available from the Organization of Teratology Information Specialists (OTIS)/MotherToBaby Pregnancy Registry in pregnant women with rheumatoid arthritis (RA) or Crohn’s disease (CD) treated with adalimumab. Registry results showed a rate of 10% for major birth defects with first trimester use of adalimumab in pregnant women with RA or CD and a rate of 7.5% for major birth defects in the disease-matched comparison cohort. The lack of pattern of major birth defects is reassuring and differences between exposure groups may have impacted the occurrence of birth defects (see Data ) . Adalimumab is actively transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in-utero exposed infant (see Clinical Considerations ) . In an embryo-fetal perinatal development study conducted in cynomolgus monkeys, no fetal harm or malformations were observed with intravenous administration of adalimumab during organogenesis and later in gestation, at doses that produced exposures up to approximately 373 times the maximum recommended human dose (MRHD) of 40 mg subcutaneous without methotrexate (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated maternal and embryo/fetal risk Published data suggest that the risk of adverse pregnancy outcomes in women with RA or inflammatory bowel disease (IBD) is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth. Fetal/Neonatal Adverse Reactions Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester ( see Data ) . Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to adalimumab products in utero [see Use in Specific Populations ( 8.4 )] . Data Human Data A prospective cohort pregnancy exposure registry conducted by OTIS/MotherToBaby in the U.S. and Canada between 2004 and 2016 compared the risk of major birth defects in live-born infants of 221 women (69 RA, 152 CD) treated with adalimumab during the first trimester and 106 women (74 RA, 32 CD) not treated with adalimumab. The proportion of major birth defects among live-born infants in the adalimumab-treated and untreated cohorts was 10% (8.7% RA, 10.5% CD) and 7.5% (6.8% RA, 9.4% CD), respectively. The lack of pattern of major birth defects is reassuring and differences between exposure groups may have impacted the occurrence of birth defects. This study cannot reliably establish whether there is an association between adalimumab and major birth defects because of methodological limitations of the registry, including small sample size, the voluntary nature of the study, and the non-randomized design. In an independent clinical study conducted in ten pregnant women with IBD treated with adalimumab, adalimumab concentrations were measured in maternal serum as well as in cord blood (n=10) and infant serum (n=8) on the day of birth. The last dose of adalimumab was given between 1 and 56 days prior to delivery. Adalimumab concentrations were 0.16-19.7 mcg/mL in cord blood, 4.28-17.7 mcg/mL in infant serum, and 0-16.1 mcg/mL in maternal serum. In all but one case, the cord blood concentration of adalimumab was higher than the maternal serum concentration, suggesting adalimumab actively crosses the placenta. In addition, one infant had serum concentrations at each of the following: 6 weeks (1.94 mcg/mL), 7 weeks (1.31 mcg/mL), 8 weeks (0.93 mcg/mL), and 11 weeks (0.53 mcg/mL), suggesting adalimumab can be detected in the serum of infants exposed in utero for at least 3 months from birth. Animal Data In an embryo-fetal perinatal development study, pregnant cynomolgus monkeys received adalimumab from gestation days 20 to 97 at doses that produced exposures up to 373 times that achieved with the MRHD without methotrexate (on an AUC basis with maternal IV doses up to 100 mg/kg/week). Adalimumab did not elicit harm to the fetuses or malformations."],"overdosage":["10 OVERDOSAGE Doses up to 10 mg/kg have been administered to patients in clinical trials without evidence of dose-limiting toxicities. In case of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions or effects and appropriate symptomatic treatment instituted immediately."],"references":["15 REFERENCES 1. National Cancer Institute. Surveillance, Epidemiology, and End Results Database (SEER) Program. SEER Incidence Crude Rates, 17 Registries, 2000-2007."],"description":["11 DESCRIPTION Adalimumab-aacf is a tumor necrosis factor blocker. Adalimumab-aacf is a recombinant human IgG1 monoclonal antibody created using phage display technology resulting in an antibody with human derived heavy and light chain variable regions and human IgG1:k constant regions. Adalimumab-aacf is produced by recombinant DNA technology in a mammalian cell (Chinese Hamster Ovary (CHO)) expression system and is purified by a process that includes specific viral inactivation and removal steps. It consists of 1330 amino acids and has a molecular weight of approximately 148 kilodaltons. IDACIO (adalimumab-aacf) injection is supplied as a sterile, preservative-free solution for subcutaneous administration. The drug product is supplied as either a single-dose, prefilled pen (IDACIO Pen), as a single-dose, 1 mL or prefilled glass syringe or as a single dose institutional use vial kit. Enclosed within the pen is a single-dose, 1 mL prefilled glass syringe. The solution of IDACIO is clear and colorless to pale yellow, with a pH of about 5.2. Each 40 mg/0.8 mL prefilled syringe or prefilled pen, or institutional use vial kit delivers 0.8 mL (40 mg) of drug product. Each 0.8 mL of IDACIO contains adalimumab-aacf (40 mg) and glacial acetic acid (0.5 mg), trehalose (54.8 mg), polysorbate 80 (0.8 mg), sodium chloride (2.3 mg), and Water for Injection. Sodium hydroxide is added to adjust pH."],"how_supplied":["16 HOW SUPPLIED/STORAGE AND HANDLING IDACIO (adalimumab-aacf) injection is supplied as a preservative-free, sterile, clear and colorless to pale yellow solution for subcutaneous administration. The following packaging configurations are available. • IDACIO Pen Carton - 40 mg/0.8 mL (2 count) IDACIO is supplied in a carton containing 2 alcohol preps and one tray. The tray contains two single-dose pens, each containing a 1 mL prefilled glass syringe with a 29 gauge staked ½ inch needle, providing 40 mg/0.8 mL of IDACIO. The syringe plunger stopper and needle cover are not made with natural rubber latex. The NDC number is 65219-554-08 • IDACIO Pen 40 mg/0.8 mL - Starter Package for Plaque Psoriasis or Uveitis (4 Count) IDACIO is supplied in a carton containing 4 alcohol preps and 2 trays (Starter Package for Plaque Psoriasis or Uveitis). Each tray contains two single-dose pens, each pen containing a 1 mL prefilled glass syringe with a 29 gauge staked ½ inch needle, providing 40 mg/0.8 mL of IDACIO. The syringe plunger stopper and needle cover are not made with natural rubber latex. The NDC number is 65219-554-28. • IDACIO Pen 40 mg/0.8 mL - Starter Package for Crohn's Disease, Ulcerative Colitis, or Hidradenitis Suppurativa (6 Count) IDACIO is supplied in a carton containing 6 alcohol preps and 3 trays (Starter Package for Crohn’s Disease, Ulcerative Colitis, or Hidradenitis Suppurativa). Each tray contains two single-dose pens, each pen containing a 1 mL prefilled glass syringe with a 29 gauge staked ½ inch 65219-628-89needle, providing 40 mg/0.8 mL of IDACIO. The syringe plunger stopper and needle cover are not made with natural rubber latex. The NDC number is 65219-554-38. • IDACIO Prefilled Syringe Carton - 40 mg/0.8 mL (2 count) IDACIO is supplied in a carton containing 2 alcohol preps and one tray. The tray contains two single-dose, 1 mL prefilled glass syringes with a 29 gauge staked ½ inch needle, each syringe providing 40 mg/0.8 mL of IDACIO. The syringe plunger stopper and needle cover are not made with natural rubber latex. The NDC number is 65219-556-18. • IDACIO Single-Dose Institutional Use Vial Kit - 40 mg/0.8 mL . IDACIO is supplied in a carton containing 1 sterile single-use syringe, 1 sterile needle, 1 vial adapter, 2 alcohol preps and 1 glass vial providing 40 mg/0.8 mL of IDACIO. The vial stopper is not made with natural rubber latex. The NDC number is 65219-558-08. Storage and Stability Do not use beyond the expiration date on the container. IDACIO must be refrigerated at 36°F to 46°F (2°C to 8°C). DO NOT FREEZE. Do not use if frozen even if it has been thawed. Store in original carton until time of administration to protect from light. If needed, for example when traveling, IDACIO may be stored at room temperature up to a maximum of 77°F (25°C) for a period of up to 28 days, with protection from light. IDACIO should be discarded if not used within the 28-day period. Record the date when IDACIO is first removed from the refrigerator in the spaces provided on the carton. Do not store IDACIO in extreme heat or cold."],"spl_medguide":["MEDICATION GUIDE IDACIO® (i-DAS-i-oh) (adalimumab-aacf) injection, for subcutaneous use Read the Medication Guide that comes with IDACIO before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking with your healthcare provider about your medical condition or treatment. What is the most important information I should know about IDACIO? IDACIO is a medicine that affects your immune system. IDACIO can lower the ability of your immune system to fight infections. Serious infections have happened in people taking adalimumab products. These serious infections include tuberculosis (TB) and infections caused by viruses, fungi or bacteria that have spread throughout the body. Some people have died from these infections. • Your healthcare provider should test you for TB before starting IDACIO. • Your healthcare provider should check you closely for signs and symptoms of TB during treatment with IDACIO. You should not start taking IDACIO if you have any kind of infection unless your healthcare provider says it is okay. Before starting IDACIO, tell your healthcare provider if you: • think you have an infection or have symptoms of an infection such as: o fever, sweats, or chills o muscle aches o cough o shortness of breath o blood in phlegm o warm, red, or painful skin or sores on your body o diarrhea or stomach pain o burning when you urinate or urinate more often than normal o feel very tired o weight loss • are being treated for an infection. • get a lot of infections or have infections that keep coming back. • have diabetes • have TB or have been in close contact with someone with TB. • were born in, lived in, or traveled to countries where there is more risk for getting TB. Ask your healthcare provider if you are not sure. • live or have lived in certain parts of the country (such as the Ohio and Mississippi River valleys) where there is an increased risk for getting certain kinds of fungal infections (histoplasmosis, coccidioidomycosis, or blastomycosis). These infections may happen or become more severe if you use IDACIO. Ask your healthcare provider if you do not know if you have lived in an area where these infections are common. • have or have had hepatitis B • use the medicine ORENCIA (abatacept), KINERET (anakinra), RITUXAN (rituximab), IMURAN (azathioprine), or PURINETHOL (6–mercaptopurine, 6-MP). • are scheduled to have major surgery. After starting IDACIO, call your healthcare provider right away if you have an infection, or any sign of an infection. IDACIO can make you more likely to get infections or make any infection that you may have worse. Cancer • For children and adults taking Tumor Necrosis Factor (TNF)-blockers, including IDACIO, the chances of getting cancer may increase. • There have been cases of unusual cancers in children, teenagers, and young adults using TNF-blockers. • People with rheumatoid arthritis (RA), especially more serious RA, may have a higher chance for getting a kind of cancer called lymphoma. • If you use TNF blockers including IDACIO your chance of getting two types of skin cancer may increase (basal cell cancer and squamous cell cancer of the skin). These types of cancer are generally not life-threatening if treated. Tell your healthcare provider if you have a bump or open sore that does not heal. • Some people receiving TNF blockers including IDACIO developed a rare type of cancer called hepatosplenic T-cell lymphoma. This type of cancer often results in death. Most of these people were male teenagers or young men. Also, most people were being treated for Crohn’s disease or ulcerative colitis with another medicine called IMURAN (azathioprine) or PURINETHOL (6-mercaptopurine, 6–MP). What is IDACIO? IDACIO is a medicine called a Tumor Necrosis Factor (TNF) blocker. IDACIO is used: • To reduce the signs and symptoms of: o moderate to severe RA in adults. IDACIO can be used alone, with methotrexate, or with certain other medicines. o moderate to severe polyarticular juvenile idiopathic arthritis (JIA) in children 2 years and older. IDACIO can be used alone, or with methotrexate. o psoriatic arthritis (PsA) in adults. IDACIO can be used alone or with certain other medicines. o ankylosing spondylitis (AS) in adults. o moderate to severe hidradenitis suppurativa (HS) in adults. • To treat moderate to severe Crohn’s disease (CD) in adults and children 6 years of age and older. • To treat moderate to severe ulcerative colitis (UC) in adults. It is not known if adalimumab products are effective in people who stopped responding to or could not tolerate TNF-blocker medicines. • To treat moderate to severe chronic (lasting a long time) plaque psoriasis (Ps) in adults who have the condition in many areas of their body and who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet light alone or with pills). • To treat non-infectious intermediate, posterior, and panuveitis in adults. What should I tell my healthcare provider before taking IDACIO? IDACIO may not be right for you. Before starting IDACIO, tell your healthcare provider about all of your medical conditions, including if you: • have an infection. See “ What is the most important information I should know about IDACIO? ” • have or have had cancer. • have any numbness or tingling or have a disease that affects your nervous system such as multiple sclerosis or Guillain-Barré syndrome. • have or had heart failure. • have recently received or are scheduled to receive a vaccine. You may receive vaccines, except for live vaccines while using IDACIO. Children should be brought up to date with all vaccines before starting IDACIO. • are allergic to IDACIO or to any of its ingredients. See the end of this Medication Guide for a list of ingredients in IDACIO. • are pregnant or plan to become pregnant, breastfeeding or plan to breastfeed. You and your healthcare provider should decide if you should take IDACIO while you are pregnant or breastfeeding. • have a baby and you were using IDACIO during your pregnancy. Tell your baby’s healthcare provider before your baby receives any vaccines. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you use: • ORENCIA (abatacept), KINERET (anakinra), REMICADE (infliximab), ENBREL (etanercept), CIMZIA (certolizumab pegol) or SIMPONI (golimumab), because you should not use IDACIO while you are also using one of these medicines. • RITUXAN (rituximab). Your healthcare provider may not want to give you IDACIO if you have received RITUXAN (rituximab) recently. • IMURAN (azathioprine) or PURINETHOL (6–mercaptopurine, 6-MP). Keep a list of your medicines with you to show your healthcare provider and pharmacist each time you get a new medicine. How should I take IDACIO? • IDACIO is given by an injection under the skin. Your healthcare provider will tell you how often to take an injection of IDACIO. This is based on your condition to be treated. Do not inject IDACIO more often than you were prescribed. • See the Instructions for Use inside the carton for complete instructions for the right way to prepare and inject IDACIO. • Make sure you have been shown how to inject IDACIO before you do it yourself. If you have any questions about giving yourself an injection, you can call your healthcare provider or the patient support program at 1-833-522-4227. Someone you know can also help you with your injection after they have been shown how to prepare and inject IDACIO. • Do not try to inject IDACIO yourself until you have been shown the right way to give the injections. If your healthcare provider decides that you or a caregiver may be able to give your injections of IDACIO at home, you should receive training on the right way to prepare and inject IDACIO. • Do not miss any doses of IDACIO unless your healthcare provider says it is okay. If you forget to take IDACIO, inject a dose as soon as you remember. Then, take your next dose at your regular scheduled time. This will put you back on schedule. In case you are not sure when to inject IDACIO, call your healthcare provider or pharmacist. • If you take more IDACIO than you were told to take, call your healthcare provider. What are the possible side effects of IDACIO? IDACIO can cause serious side effects, including: See “What is the most important information I should know about IDACIO?” • Serious Infections. Your healthcare provider will examine you for TB and perform a test to see if you have TB. If your healthcare provider feels that you are at risk for TB, you may be treated with medicine for TB before you begin treatment with IDACIO and during treatment with IDACIO. Even if your TB test is negative your healthcare provider should carefully monitor you for TB infections while you are taking IDACIO. People who had a negative TB skin test before receiving adalimumab products have developed active TB. Tell your healthcare provider if you have any of the following symptoms while taking or after taking IDACIO: o cough that does not go away o weight loss o low grade fever o loss of body fat and muscle (wasting) • Hepatitis B infection in people who carry the virus in their blood. If you are a carrier of the hepatitis B virus (a virus that affects the liver), the virus can become active while you use IDACIO. Your healthcare provider should do blood tests before you start treatment, while you are using IDACIO, and for several months after you stop treatment with IDACIO. Tell your healthcare provider if you have any of the following symptoms of a possible hepatitis B infection: o muscle aches o feel very tired o dark urine o skin or eyes look yellow o little or no appetite o vomiting o clay-colored bowel movements o fever o chills o stomach discomfort o skin rash • Allergic reactions. Allergic reactions can happen in people who use IDACIO. Call your healthcare provider or get medical help right away if you have any of these symptoms of a serious allergic reaction: o Hives o trouble breathing o swelling of your face, eyes, lips or mouth • Nervous system problems. Signs and symptoms of a nervous system problem include numbness or tingling, problems with your vision, weakness in your arms or legs, and dizziness. • Blood problems. Your body may not make enough of the blood cells that help fight infections or help to stop bleeding. Symptoms include a fever that does not go away, bruising or bleeding very easily, or looking very pale. • New heart failure or worsening of heart failure you already have. Call your healthcare provider right away if you get new worsening symptoms of heart failure while taking IDACIO, including: o shortness of breath o sudden weight gain o swelling of your ankles or feet • Immune reactions including a lupus-like syndrome. Symptoms include chest discomfort or pain that does not go away, shortness of breath, joint pain, or a rash on your cheeks or arms that gets worse in the sun. Symptoms may improve when you stop IDACIO. • Liver Problems. Liver problems can happen in people who use TNF-blocker medicines. These problems can lead to liver failure and death. Call your healthcare provider right away if you have any of these symptoms: o feel very tired o poor appetite or vomiting o skin or eyes look yellow o pain on the right side of your stomach (abdomen) • Psoriasis. Some people using adalimumab products had new psoriasis or worsening of psoriasis they already had. Tell your healthcare provider if you develop red scaly patches or raised bumps that are filled with pus. Your healthcare provider may decide to stop your treatment with IDACIO. Call your healthcare provider or get medical care right away if you develop any of the above symptoms. Your treatment with IDACIO may be stopped. The most common side effects of IDACIO include: • injection site reactions: redness, rash, swelling, itching, or bruising. These symptoms usually will go away within a few days. Call your healthcare provider right away if you have pain, redness or swelling around the injection site that does not go away within a few days or gets worse. • upper respiratory infections (including sinus infections). • headaches. • rash. These are not all the possible side effects with IDACIO. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. Ask your healthcare provider or pharmacist for more information. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store IDACIO? • Store IDACIO in the refrigerator at 36ºF to 46ºF (2ºC to 8ºC). Store IDACIO in the original carton until use to protect it from light. • Do not freeze IDACIO . Do not use IDACIO if frozen, even if it has been thawed. • Refrigerated IDACIO may be used until the expiration date printed on the IDACIO carton. Pen or prefilled syringe. Do not use IDACIO after the expiration date. • If needed, for example when you are traveling, you may also store IDACIO at room temperature up to 77°F (25°C) for up to 28 days. Store IDACIO in the original carton until use, to protect it from light. • Throw away IDACIO if it has been kept at room temperature and not been used within 28 days. • Record the date you first remove IDACIO from the refrigerator in the spaces provided on the carton. • Do not store IDACIO in extreme heat or cold. • Do not use a Pen or prefilled syringe if the liquid is cloudy, discolored, or has flakes or particles in it. • Do not drop or crush IDACIO. The prefilled syringe is glass. Keep IDACIO, injection supplies, and all other medicines out of the reach of children. General information about the safe and effective use of IDACIO. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use IDACIO for a condition for which it was not prescribed. Do not give IDACIO to other people, even if they have the same condition. It may harm them. This Medication Guide summarizes the most important information about IDACIO. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about IDACIO that is written for health professionals. What are the ingredients in IDACIO? Active ingredient: adalimumab-aacf IDACIO 40 mg/0.8 mL Pen, IDACIO 40 mg/0.8 mL prefilled syringe and IDACIO 40 mg/0.8 mL institutional use vial kit. Inactive ingredients: glacial acetic acid, trehalose, polysorbate 80, sodium chloride and Water for Injection. Sodium hydroxide is added as necessary to adjust pH. Manufactured by: Fresenius Kabi USA, LLC, Lake Zurich, IL 60047, U.S.A. For more product information go to www.IDACIO.com You can enroll in a patient support program by calling 1-833-522-4227 or visiting the patient support program website: https://kabicare.us/. U.S. License number 2146 This Medication Guide has been approved by the U.S. Food and Drug Administration Approved: Jan/2024"],"boxed_warning":["WARNING: SERIOUS INFECTIONS and MALIGNANCY SERIOUS INFECTIONS Patients treated with adalimumab products including IDACIO are at increased risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions ( 5.1 )] . Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue IDACIO if a patient develops a serious infection or sepsis. Reported infections include: • Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Test patients for latent TB before IDACIO use and during therapy. Initiate treatment for latent TB prior to IDACIO use. • Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric anti- fungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness. • Bacterial, viral and other infections due to opportunistic pathogens, including Legionella and Listeria. Carefully consider the risks and benefits of treatment with IDACIO prior to initiating therapy in patients with chronic or recurrent infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with IDACIO, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )] . MALIGNANCY Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers including adalimumab products [see Warnings and Precautions ( 5.2 )] . Post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including adalimumab products. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn's disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all these patients had received treatment with azathioprine or 6‑mercaptopurine (6–MP) concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants [see Warnings and Precautions ( 5.2 )] WARNING: SERIOUS INFECTIONS and MALIGNANCY See full prescribing information for complete boxed warning. SERIOUS INFECTIONS ( 5.1 , 6.1 ): • Increased risk of serious infections leading to hospitalization or death, including tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as histoplasmosis), and infections due to other opportunistic pathogens. • Discontinue IDACIO if a patient develops a serious infection or sepsis during treatment. • Perform test for latent TB; if positive, start treatment for TB prior to starting IDACIO. • Monitor all patients for active TB during treatment, even if initial latent TB test is negative. MALIGNANCY ( 5.2 ): • Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers including adalimumab products. • Post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have occurred in adolescent and young adults with inflammatory bowel disease treated with TNF blockers including adalimumab products."],"geriatric_use":["8.5 Geriatric Use A total of 519 RA patients 65 years of age and older, including 107 patients 75 years of age and older, received adalimumab in clinical studies RA-I through IV. No overall difference in effectiveness was observed between these patients and younger patients. The frequency of serious infection and malignancy among adalimumab treated patients 65 years of age and older was higher than for those less than 65 years of age. Consider the benefits and risks of IDACIO in patients 65 years of age and older. In patients treated with IDACIO, closely monitor for the development of infection or malignancy [see Warnings and Precautions ( 5.1 , 5.2 )] ."],"effective_time":"20241015","clinical_studies":["14 CLINICAL STUDIES 14.1 Rheumatoid Arthritis The efficacy and safety of adalimumab were assessed in five randomized, double-blind studies in patients ≥18 years of age with active rheumatoid arthritis (RA) diagnosed according to American College of Rheumatology (ACR) criteria. Patients had at least 6 swollen and 9 tender joints. Adalimumab was administered subcutaneously in combination with methotrexate (MTX) (12.5 to 25 mg, Studies RA-I, RA-III and RA-V) or as monotherapy (Studies RA-II and RA-V) or with other disease-modifying anti-rheumatic drugs (DMARDs) (Study RA-IV). Study RA-I evaluated 271 patients who had failed therapy with at least one but no more than four DMARDs and had inadequate response to MTX. Doses of 20, 40 or 80 mg of adalimumab or placebo were given every other week for 24 weeks. Study RA-II evaluated 544 patients who had failed therapy with at least one DMARD. Doses of placebo, 20 or 40 mg of adalimumab were given as monotherapy every other week or weekly for 26 weeks. Study RA-III evaluated 619 patients who had an inadequate response to MTX. Patients received placebo, 40 mg of adalimumab every other week with placebo injections on alternate weeks, or 20 mg of adalimumab weekly for up to 52 weeks. Study RA-III had an additional primary endpoint at 52 weeks of inhibition of disease progression (as detected by X-ray results). Upon completion of the first 52 weeks, 457 patients enrolled in an open-label extension phase in which 40 mg of adalimumab was administered every other week for up to 5 years. Study RA-IV assessed safety in 636 patients who were either DMARD-naive or were permitted to remain on their pre-existing rheumatologic therapy provided that therapy was stable for a minimum of 28 days. Patients were randomized to 40 mg of adalimumab or placebo every other week for 24 weeks. Study RA-V evaluated 799 patients with moderately to severely active RA of less than 3 years duration who were ≥18 years old and MTX naïve. Patients were randomized to receive either MTX (optimized to 20 mg/week by week 8), adalimumab 40 mg every other week or adalimumab/MTX combination therapy for 104 weeks. Patients were evaluated for signs and symptoms, and for radiographic progression of joint damage. The median disease duration among patients enrolled in the study was 5 months. The median MTX dose achieved was 20 mg. Clinical Response The percent of adalimumab treated patients achieving ACR 20, 50 and 70 responses in Studies RA‑II and III are shown in Table 3 . Table 3: ACR Responses in Studies RA-II and RA-III (Percent of Patients) Study RA-II Monotherapy (26 weeks) Study RA-III Methotrexate Combination (24 and 52 weeks) Response Placebo Adalimumab Adalimumab Placebo/MTX Adalimumab/MTX 40 mg every 40 mg weekly 40 mg every other week other week N=110 N=113 N=103 N=200 N=207 ACR20 Month 6 19% 46% * 53% * 30% 63% * Month 12 NA NA NA 24% 59% * ACR50 Month 6 8% 22% * 35% * 10% 39% * Month 12 NA NA NA 10% 42% * ACR70 Month 6 2% 12% * 18% * 3% 21% * Month 12 NA NA NA 5% 23% * * p<0.01, adalimumab vs. placebo The results of Study RA-I were similar to Study RA-III; patients receiving adalimumab 40 mg every other week in Study RA-I also achieved ACR 20, 50 and 70 response rates of 65%, 52% and 24%, respectively, compared to placebo responses of 13%, 7% and 3% respectively, at 6 months (p<0.01). The results of the components of the ACR response criteria for Studies RA-II and RA-III are shown in Table 4 . ACR response rates and improvement in all components of ACR response were maintained to week 104. Over the 2 years in Study RA-III, 20% of adalimumab patients receiving 40 mg every other week achieved a major clinical response, defined as maintenance of an ACR 70 response over a 6-month period. ACR responses were maintained in similar proportions of patients for up to 5 years with continuous adalimumab treatment in the open-label portion of Study RA-III. Table 4: Components of ACR Response in Studies RA-II and RA-III Study RA-II Study RA-III Parameter (median) Placebo N=110 Adalimumab a N=113 Placebo/MTX N=200 Adalimumab a /MTX N=207 Baseline Wk 26 Baseline Wk 26 Baseline Wk 24 Baseline Wk 24 Number of tender joints (0-68) 35 26 31 16 * 26 15 24 8 * Number of swollen joints (0-66) 19 16 18 10 * 17 11 18 5 * Physician global assessment b 7.0 6.1 6.6 3.7 * 6.3 3.5 6.5 2.0 * Patient global assessment b 7.5 6.3 7.5 4.5 * 5.4 3.9 5.2 2.0 * Pain b 7.3 6.1 7.3 4.1 * 6.0 3.8 5.8 2.1 * Disability index (HAQ) c 2.0 1.9 1.9 1.5 * 1.5 1.3 1.5 0.8 * CRP (mg/dL) 3.9 4.3 4.6 1.8 * 1.0 0.9 1.0 0.4 * a 40 mg adalimumab administered every other week b Visual analogue scale; 0 = best, 10 = worst c Disability Index of the Health Assessment Questionnaire; 0 = best, 3 = worst, measures the patient’s ability to perform the following: dress/groom, arise, eat, walk, reach, grip, maintain hygiene, and maintain daily activity * p<0.001, adalimumab vs. placebo, based on mean change from baseline The time course of ACR 20 response for Study RA-III is shown in Figure 1 . In Study RA-III, 85% of patients with ACR 20 responses at week 24 maintained the response at 52 weeks. The time course of ACR 20 response for Study RA-I and Study RA-II were similar. Figure 1: Study RA-III ACR 20 Responses over 52 Weeks In Study RA-IV, 53% of patients treated with adalimumab 40 mg every other week plus standard of care had an ACR 20 response at week 24 compared to 35% on placebo plus standard of care (p<0.001). No unique adverse reactions related to the combination of adalimumab and other DMARDs were observed. In Study RA-V with MTX naïve patients with recent onset RA, the combination treatment with adalimumab plus MTX led to greater percentages of patients achieving ACR responses than either MTX monotherapy or adalimumab monotherapy at Week 52 and responses were sustained at Week 104 (see Table 5 ). Table 5: ACR Response in Study RA-V (Percent of Patients) Response MTX b N=257 Adalimumab c N=274 Adalimumab/MTX N=268 ACR20 Week 52 Week 104 63% 56% 54% 49% 73% 69% ACR50 Week 52 Week 104 46% 43% 41% 37% 62% 59% ACR70 Week 52 Week 104 27% 28% 26% 28% 46% 47% Major Clinical Response a 28% 25% 49% a Major clinical response is defined as achieving an ACR70 response for a continuous six month period b p<0.05, adalimumab/MTX vs. MTX for ACR 20 p<0.001, adalimumab/MTX vs. MTX for ACR 50 and 70, and Major Clinical Response c p<0.001, adalimumab/MTX vs. adalimumab At Week 52, all individual components of the ACR response criteria for Study RA-V improved in the adalimumab/MTX group and improvements were maintained to Week 104. Radiographic Response In Study RA-III, structural joint damage was assessed radiographically and expressed as change in Total Sharp Score (TSS) and its components, the erosion score and Joint Space Narrowing (JSN) score, at month 12 compared to baseline. At baseline, the median TSS was approximately 55 in the placebo and 40 mg every other week groups. The results are shown in Table 6 . Adalimumab/MTX treated patients demonstrated less radiographic progression than patients receiving MTX alone at 52 weeks. Table 6: Radiographic Mean Changes Over 12 Months in Study RA-III Placebo/MTX Adalimumab/MTX 40 mg every other week Placebo/MTX‑Adalimumab/MTX (95% Confidence Interval*) P-value** Total Sharp score 2.7 0.1 2.6 (1.4, 3.8) <0.001 Erosion score 1.6 0.0 1.6 (0.9, 2.2) <0.001 JSN score 1.0 0.1 0.9 (0.3, 1.4) 0.002 *95% confidence intervals for the differences in change scores between MTX and adalimumab. **Based on rank analysis In the open-label extension of Study RA-III, 77% of the original patients treated with any dose of adalimumab were evaluated radiographically at 2 years. Patients maintained inhibition of structural damage, as measured by the TSS. Fifty-four percent had no progression of structural damage as defined by a change in the TSS of zero or less. Fifty-five percent (55%) of patients originally treated with 40 mg adalimumab every other week have been evaluated radiographically at 5 years. Patients had continued inhibition of structural damage with 50% showing no progression of structural damage defined by a change in the TSS of zero or less. In Study RA-V, structural joint damage was assessed as in Study RA-III. Greater inhibition of radiographic progression, as assessed by changes in TSS, erosion score and JSN was observed in the adalimumab/MTX combination group as compared to either the MTX or adalimumab monotherapy group at Week 52 as well as at Week 104 (see Table 7 ). Table 7: Radiographic Mean Change* in Study RA-V MTX a N=257 Adalimumab a , b N=274 Adalimumab/MTX N=268 52 Weeks Total Sharp score 5.7 (4.2, 7.3) 3.0 (1.7, 4.3) 1.3 (0.5, 2.1) Erosion score 3.7 (2.7, 4.8) 1.7 (1.0, 2.4) 0.8 (0.4, 1.2) JSN score 2.0 (1.2, 2.8) 1.3 (0.5, 2.1) 0.5 (0.0, 1.0) 104 Weeks Total Sharp score 10.4 (7.7, 13.2) 5.5 (3.6, 7.4) 1.9 (0.9, 2.9) Erosion score 6.4 (4.6, 8.2) 3.0 (2.0, 4.0) 1.0 (0.4, 1.6) JSN score 4.1 (2.7, 5.4) 2.6 (1.5, 3.7) 0.9 (0.3, 1.5) * mean (95% confidence interval) a p<0.001, adalimumab /MTX vs. MTX at 52 and 104 weeks and for adalimumab /MTX vs adalimumab at 104 weeks b p<0.01, for adalimumab /MTX vs. adalimumab at 52 weeks Physical Function Response In studies RA-I through IV, adalimumab showed significantly greater improvement than placebo in the disability index of Health Assessment Questionnaire (HAQ-DI) from baseline to the end of study, and significantly greater improvement than placebo in the health-outcomes as assessed by The Short Form Health Survey (SF 36). Improvement was seen in both the Physical Component Summary (PCS) and the Mental Component Summary (MCS). In Study RA-III, the mean (95% CI) improvement in HAQ-DI from baseline at week 52 was 0.60 (0.55, 0.65) for the adalimumab patients and 0.25 (0.17, 0.33) for placebo/MTX (p<0.001) patients. Sixty-three percent of adalimumab-treated patients achieved a 0.5 or greater improvement in HAQ-DI at week 52 in the double-blind portion of the study. Eighty-two percent of these patients maintained that improvement through week 104 and a similar proportion of patients maintained this response through week 260 (5 years) of open-label treatment. Mean improvement in the SF-36 was maintained through the end of measurement at week 156 (3 years). In Study RA-V, the HAQ-DI and the physical component of the SF-36 showed greater improvement (p<0.001) for the adalimumab/MTX combination therapy group versus either the MTX monotherapy or the adalimumab monotherapy group at Week 52, which was maintained through Week 104. adali-graph-01.jpg 14.2 Juvenile Idiopathic Arthritis The safety and efficacy of adalimumab was assessed in two studies (Studies JIA-I and JIA-II) in patients with active polyarticular juvenile idiopathic arthritis (JIA). Study JIA-I The safety and efficacy of adalimumab were assessed in a multicenter, randomized, withdrawal, double-blind, parallel-group study in 171 patients who were 4 to 17 years of age with polyarticular JIA. In the study, the patients were stratified into two groups: MTX-treated or non‑MTX-treated. All patients had to show signs of active moderate or severe disease despite previous treatment with NSAIDs, analgesics, corticosteroids, or DMARDS. Patients who received prior treatment with any biologic DMARDS were excluded from the study. The study included four phases: an open-label lead in phase (OL-LI; 16 weeks), a double-blind randomized withdrawal phase (DB; 32 weeks), an open-label extension phase (OLE-BSA; up to 136 weeks), and an open-label fixed dose phase (OLE-FD; 16 weeks). In the first three phases of the study, adalimumab was administered based on body surface area at a dose of 24 mg/m 2 up to a maximum total body dose of 40 mg subcutaneously (SC) every other week. In the OLE-FD phase, the patients were treated with 20 mg of adalimumab SC every other week if their weight was less than 30 kg and with 40 mg of adalimumab SC every other week if their weight was 30 kg or greater. Patients remained on stable doses of NSAIDs and or prednisone (≤0.2 mg/kg/day or 10 mg/day maximum). Patients demonstrating a Pediatric ACR 30 response at the end of OL-LI phase were randomized into the double blind (DB) phase of the study and received either adalimumab or placebo every other week for 32 weeks or until disease flare. Disease flare was defined as a worsening of ≥30% from baseline in ≥3 of 6 Pediatric ACR core criteria, ≥2 active joints, and improvement of >30% in no more than 1 of the 6 criteria. After 32 weeks or at the time of disease flare during the DB phase, patients were treated in the open-label extension phase based on the BSA regimen (OLE‑ BSA), before converting to a fixed dose regimen based on body weight (OLE-FD phase). Study JIA-I Clinical Response At the end of the 16-week OL-LI phase, 94% of the patients in the MTX stratum and 74% of the patients in the non-MTX stratum were Pediatric ACR 30 responders. In the DB phase significantly fewer patients who received adalimumab experienced disease flare compared to placebo, both without MTX (43% vs. 71%) and with MTX (37% vs. 65%). More patients treated with adalimumab continued to show pediatric ACR 30/50/70 responses at Week 48 compared to patients treated with placebo. Pediatric ACR responses were maintained for up to two years in the OLE phase in patients who received adalimumab throughout the study. Study JIA-II Adalimumab was assessed in an open-label, multicenter study in 32 patients who were 2 to <4 years of age or 4 years of age and older weighing <15 kg with moderately to severely active polyarticular JIA. Most patients (97%) received at least 24 weeks of adalimumab treatment dosed 24 mg/m 2 up to a maximum of 20 mg every other week as a single SC injection up to a maximum of 120 weeks duration. During the study, most patients used concomitant MTX, with fewer reporting use of corticosteroids or NSAIDs. The primary objective of the study was evaluation of safety [see Adverse Reactions ( 6.1 )] . 14.3 Psoriatic Arthritis The safety and efficacy of adalimumab was assessed in two randomized, double-blind, placebo controlled studies in 413 patients with psoriatic arthritis (PsA). Upon completion of both studies, 383 patients enrolled in an open-label extension study, in which 40 mg adalimumab was administered every other week. Study PsA-I enrolled 313 adult patients with moderately to severely active PsA (>3 swollen and >3 tender joints) who had an inadequate response to NSAID therapy in one of the following forms: (1) distal interphalangeal (DIP) involvement (N=23); (2) polyarticular arthritis (absence of rheumatoid nodules and presence of plaque psoriasis) (N=210); (3) arthritis mutilans (N=1); (4) asymmetric PsA (N=77); or (5) AS-like (N=2). Patients on MTX therapy (158 of 313 patients) at enrollment (stable dose of ≤30 mg/week for >1 month) could continue MTX at the same dose. Doses of adalimumab 40 mg or placebo every other week were administered during the 24-week double-blind period of the study. Compared to placebo, treatment with adalimumab resulted in improvements in the measures of disease activity (see Tables 8 and 9 ). Among patients with PsA who received adalimumab, the clinical responses were apparent in some patients at the time of the first visit (two weeks) and were maintained up to 88 weeks in the ongoing open-label study. Similar responses were seen in patients with each of the subtypes of psoriatic arthritis, although few patients were enrolled with the arthritis mutilans and ankylosing spondylitis-like subtypes. Responses were similar in patients who were or were not receiving concomitant MTX therapy at baseline. Patients with psoriatic involvement of at least three percent body surface area (BSA) were evaluated for Psoriatic Area and Severity Index (PASI) responses. At 24 weeks, the proportions of patients achieving a 75% or 90% improvement in the PASI were 59% and 42% respectively, in the adalimumab group (N=69), compared to 1% and 0% respectively, in the placebo group (N=69) (p<0.001). PASI responses were apparent in some patients at the time of the first visit (two weeks). Responses were similar in patients who were or were not receiving concomitant MTX therapy at baseline. Table 8: ACR Response in Study PsA-I (Percent of Patients) Placebo N=162 Adalimumab* N=151 ACR20 Week 12 Week 24 14% 15% 58% 57% ACR50 Week 12 Week 24 4% 6% 36% 39% ACR70 Week 12 Week 24 1% 1% 20% 23% * p<0.001 for all comparisons between adalimumab and placebo Table 9: Components of Disease Activity in Study PsA-I Placebo N=162 Adalimumab* N=151 Parameter: median Baseline 24 weeks Baseline 24 weeks Number of tender joints a 23.0 17.0 20.0 5.0 Number of swollen joints b 11.0 9.0 11.0 3.0 Physician global assessment c 53.0 49.0 55.0 16.0 Patient global assessment c 49.5 49.0 48.0 20.0 Pain c 49.0 49.0 54.0 20.0 Disability index (HAQ) d 1.0 0.9 1.0 0.4 CRP (mg/dL) e 0.8 0.7 0.8 0.2 * p<0.001 for adalimumab vs. placebo comparisons based on median changes a Scale 0-78 b Scale 0-76 c Visual analog scale; 0=best, 100=worst d Disability Index of the Health Assessment Questionnaire; 0=best, 3=worst; measures the patient’s ability to perform the following: dress/groom, arise, eat, walk, reach, grip, maintain hygiene, and maintain daily activity. e Normal range: 0-0.287 mg/dL Similar results were seen in an additional, 12-week study in 100 patients with moderate to severe psoriatic arthritis who had suboptimal response to DMARD therapy as manifested by ≥3 tender joints and ≥3 swollen joints at enrollment. Radiographic Response Radiographic changes were assessed in the PsA studies. Radiographs of hands, wrists, and feet were obtained at baseline and Week 24 during the double-blind period when patients were on adalimumab or placebo and at Week 48 when all patients were on open-label adalimumab. A modified Total Sharp Score (mTSS), which included distal interphalangeal joints (i.e., not identical to the TSS used for rheumatoid arthritis), was used by readers blinded to treatment group to assess the radiographs. Adalimumab-treated patients demonstrated greater inhibition of radiographic progression compared to placebo-treated patients and this effect was maintained at 48 weeks (see Table 10 ). Table 10: Change in Modified Total Sharp Score in Psoriatic Arthritis Placebo N=141 Adalimumab N=133 Week 24 Week 24 Week 48 Baseline mean 22.1 23.4 23.4 Mean Change ± SD 0.9 ± 3.1 -0.1 ± 1.7 -0.2 ± 4.9* * <0.001 for the difference between adalimumab, Week 48 and Placebo, Week 24 (primary analysis) Physical Function Response In Study PsA-I, physical function and disability were assessed using the HAQ Disability Index (HAQ-DI) and the SF-36 Health Survey. Patients treated with 40 mg of adalimumab every other week showed greater improvement from baseline in the HAQ-DI score (mean decreases of 47% and 49% at Weeks 12 and 24 respectively) in comparison to placebo (mean decreases of 1% and 3% at Weeks 12 and 24 respectively). At Weeks 12 and 24, patients treated with adalimumab showed greater improvement from baseline in the SF-36 Physical Component Summary score compared to patients treated with placebo, and no worsening in the SF-36 Mental Component Summary score. Improvement in physical function based on the HAQ-DI was maintained for up to 84 weeks through the open-label portion of the study. 14.4 Ankylosing Spondylitis The safety and efficacy of adalimumab 40 mg every other week was assessed in 315 adult patients in a randomized, 24 week double-blind, placebo-controlled study in patients with active ankylosing spondylitis (AS) who had an inadequate response to glucocorticoids, NSAIDs, analgesics, methotrexate or sulfasalazine. Active AS was defined as patients who fulfilled at least two of the following three criteria: (1) a Bath AS disease activity index (BASDAI) score ≥4 cm, (2) a visual analog score (VAS) for total back pain ≥ 40 mm, and (3) morning stiffness ≥ 1 hour. The blinded period was followed by an open-label period during which patients received adalimumab 40 mg every other week subcutaneously for up to an additional 28 weeks. Improvement in measures of disease activity was first observed at Week 2 and maintained through 24 weeks as shown in Figure 2 and Table 11 . Responses of patients with total spinal ankylosis (n=11) were similar to those without total ankylosis. Figure 2. ASAS 20 Response By Visit, Study AS- At 12 weeks, the ASAS 20/50/70 responses were achieved by 58%, 38%, and 23%, respectively, of patients receiving adalimumab, compared to 21%, 10%, and 5% respectively, of patients receiving placebo (p <0.001). Similar responses were seen at Week 24 and were sustained in patients receiving open-label adalimumab for up to 52 weeks. A greater proportion of patients treated with adalimumab (22%) achieved a low level of disease activity at 24 weeks (defined as a value <20 [on a scale of 0 to 100 mm] in each of the four ASAS response parameters) compared to patients treated with placebo (6%). Table 11: Components of Ankylosing Spondylitis Disease Activity Placebo N=107 Adalimumab N=208 Baseline mean Week 24 mean Baseline mean Week 24 mean ASAS 20 Response Criteria* Patient’s Global Assessment of Disease Activity a * 65 60 63 38 Total back pain* 67 58 65 37 Inflammation b * 6.7 5.6 6.7 3.6 BASFI c * 56 51 52 34 BASDAI d score* 6.3 5.5 6.3 3.7 BASMI e score* 4.2 4.1 3.8 3.3 Tragus to wall (cm) 15.9 15.8 15.8 15.4 Lumbar flexion (cm) 4.1 4.0 4.2 4.4 Cervical rotation (degrees) 42.2 42.1 48.4 51.6 Lumbar side flexion (cm) 8.9 9.0 9.7 11.7 Intermalleolar distance (cm) 92.9 94.0 93.5 100.8 CRP f * 2.2 2.0 1.8 0.6 a Percent of subjects with at least a 20% and 10-unit improvement measured on a Visual Analog Scale (VAS) with 0 = “none” and 100 = “severe” b mean of questions 5 and 6 of BASDAI (defined in ‘d’) c Bath Ankylosing Spondylitis Functional Index d Bath Ankylosing Spondylitis Disease Activity Index e Bath Ankylosing Spondylitis Metrology Index f C-Reactive Protein (mg/dL) * statistically significant for comparisons between adalimumab and placebo at Week 24 A second randomized, multicenter, double-blind, placebo-controlled study of 82 patients with ankylosing spondylitis showed similar results. Patients treated with adalimumab achieved improvement from baseline in the Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) score (-3.6 vs. -1.1) and in the Short Form Health Survey (SF-36) Physical Component Summary (PCS) score (7.4 vs. 1.9) compared to placebo-treated patients at Week 24. adali-graph-02.jpg 14.5 Adult Crohn’s Disease The safety and efficacy of multiple doses of adalimumab were assessed in adult patients with moderately to severely active Crohn’s disease, CD, (Crohn’s Disease Activity Index (CDAI) ≥ 220 and ≤ 450) in randomized, double-blind, placebo-controlled studies. Concomitant stable doses of aminosalicylates, corticosteroids, and/or immunomodulatory agents were permitted, and 79% of patients continued to receive at least one of these medications. Induction of clinical remission (defined as CDAI < 150) was evaluated in two studies. In Study CD-I, 299 TNF-blocker naïve patients were randomized to one of four treatment groups: the placebo group received placebo at Weeks 0 and 2, the 160/80 group received 160 mg adalimumab at Week 0 and 80 mg at Week 2, the 80/40 group received 80 mg at Week 0 and 40 mg at Week 2, and the 40/20 group received 40 mg at Week 0 and 20 mg at Week 2. Clinical results were assessed at Week 4. In the second induction study, Study CD-II, 325 patients who had lost response to, or were intolerant to, previous infliximab therapy were randomized to receive either 160 mg adalimumab at Week 0 and 80 mg at Week 2, or placebo at Weeks 0 and 2. Clinical results were assessed at Week 4. Maintenance of clinical remission was evaluated in Study CD-III. In this study, 854 patients with active disease received open-label adalimumab, 80 mg at week 0 and 40 mg at Week 2. Patients were then randomized at Week 4 to 40 mg adalimumab every other week, 40 mg adalimumab every week, or placebo. The total study duration was 56 weeks. Patients in clinical response (decrease in CDAI ≥70) at Week 4 were stratified and analyzed separately from those not in clinical response at Week 4. Induction of Clinical Remission A greater percentage of the patients treated with 160/80 mg adalimumab achieved induction of clinical remission versus placebo at Week 4 regardless of whether the patients were TNF blocker naïve (CD-I), or had lost response to or were intolerant to infliximab (CD-II) (see Table 12 ). Table 12: Induction of Clinical Remission in Studies CD-I and CD-II (Percent of Patients) CD-I CD-II Placebo N=74 Adalimumab 160/80 mg N=76 Placebo N=166 Adalimumab 160/80 mg N=159 Week 4 Clinical remission 12% 36%* 7% 21%* Clinical response 34% 58%** 34% 52%** Clinical remission is CDAI score < 150; clinical response is decrease in CDAI of at least 70 points. * p<0.001 for adalimumab vs. placebo pairwise comparison of proportions ** p<0.01 for adalimumab vs. placebo pairwise comparison of proportions Maintenance of Clinical Remission In Study CD-III at Week 4, 58% (499/854) of patients were in clinical response and were assessed in the primary analysis. At Weeks 26 and 56, greater proportions of patients who were in clinical response at Week 4 achieved clinical remission in the adalimumab 40 mg every other week maintenance group compared to patients in the placebo maintenance group (see Table 13 ). The group that received adalimumab therapy every week did not demonstrate significantly higher remission rates compared to the group that received adalimumab every other week. Table 13: Maintenance of Clinical Remission in CD-III (Percent of Patients) Placebo 40 mg Adalimumab every other week N=170 N=172 Week 26 Clinical remission 17% 40%* Clinical response 28% 54%* Week 56 Clinical remission 12% 36%* Clinical response 18% 43%* Clinical remission is CDAI score < 150; clinical response is decrease in CDAI of at least 70 points. *p<0.001 for adalimumab vs. placebo pairwise comparisons of proportions Of those in response at Week 4 who attained remission during the study, patients in the adalimumab every other week group maintained remission for a longer time than patients in the placebo maintenance group. Among patients who were not in response by Week 12, therapy continued beyond 12 weeks did not result in significantly more responses. 14.6 Pediatric Crohn’s Disease A randomized, double-blind, 52-week clinical study of 2 dose concentrations of adalimumab (Study PCD-I) was conducted in 192 pediatric patients (6 to 17 years of age) with moderately to severely active Crohn’s disease (defined as Pediatric Crohn’s Disease Activity Index (PCDAI) score > 30). Enrolled patients had over the previous two year period an inadequate response to corticosteroids or an immunomodulator (i.e., azathioprine, 6-mercaptopurine, or methotrexate). Patients who had previously received a TNF blocker were allowed to enroll if they had previously had loss of response or intolerance to that TNF blocker. Patients received open-label induction therapy at a dose based on their body weight (≥40 kg and <40 kg). Patients weighing ≥40 kg received 160 mg (at Week 0) and 80 mg (at Week 2). Patients weighing <40 kg received 80 mg (at Week 0) and 40 mg (at Week 2). At Week 4, patients within each body weight category (≥40 kg and <40 kg) were randomized 1:1 to one of two maintenance dose regimens (high dose and low dose). The high dose was 40 mg every other week for patients weighing ≥40 kg and 20 mg every other week for patients weighing <40 kg. The low dose was 20 mg every other week for patients weighing ≥40 kg and 10 mg every other week for patients weighing <40 kg. Concomitant stable dosages of corticosteroids (prednisone dosage ≤40 mg/day or equivalent) and immunomodulators (azathioprine, 6-mercaptopurine, or methotrexate) were permitted throughout the study. At Week 12, patients who experienced a disease flare (increase in PCDAI of ≥ 15 from Week 4 and absolute PCDAI > 30) or who were non-responders (did not achieve a decrease in the PCDAI of ≥ 15 from baseline for 2 consecutive visits at least 2 weeks apart) were allowed to dose-escalate (i.e., switch from blinded every other week dosing to blinded every week dosing); patients who dose-escalated were considered treatment failures. At baseline, 38% of patients were receiving corticosteroids, and 62% of patients were receiving an immunomodulator. Forty-four percent (44%) of patients had previously lost response or were intolerant to a TNF blocker. The median baseline PCDAI score was 40. Of the 192 patients total, 188 patients completed the 4 week induction period, 152 patients completed 26 weeks of treatment, and 124 patients completed 52 weeks of treatment. Fifty-one percent (51%) (48/95) of patients in the low maintenance dose group dose-escalated, and 38% (35/93) of patients in the high maintenance dose group dose-escalated. At Week 4, 28% (52/188) of patients were in clinical remission (defined as PCDAI ≤ 10). The proportions of patients in clinical remission (defined as PCDAI ≤ 10) and clinical response (defined as reduction in PCDAI of at least 15 points from baseline) were assessed at Weeks 26 and 52. At both Weeks 26 and 52, the proportion of patients in clinical remission and clinical response was numerically higher in the high dose group compared to the low dose group ( Table 14 ). The recommended maintenance regimen is 20 mg every other week for patients weighing < 40 kg and 40 mg every other week for patients weighing ≥ 40 kg. Every week dosing is not the recommended maintenance dosing regimen [see Dosage and Administration ( 2.3 )] . Table 14: Clinical Remission and Clinical Response in Study PCD-I Low Maintenance Dose † (20 or 10 mg every other week) N = 95 High Maintenance Dose # (40 or 20 mg every other week) N = 93 Week 26 Clinical Remission ‡ 28% 39% Clinical Response § 48% 59% Week 52 Clinical Remission ‡ 23% 33% Clinical Response § 28% 42% † The low maintenance dose was 20 mg every other week for patients weighing ≥ 40 kg and 10 mg every other week for patients weighing < 40 kg. # The high maintenance dose was 40 mg every other week for patients weighing ≥ 40 kg and 20 mg every other week for patients weighing < 40 kg. ‡ Clinical remission defined as PCDAI ≤ 10. § Clinical response defined as reduction in PCDAI of at least 15 points from baseline. 14.7 Adult Ulcerative Colitis The safety and efficacy of adalimumab were assessed in adult patients with moderately to severely active ulcerative colitis (Mayo score 6 to 12 on a 12 point scale, with an endoscopy subscore of 2 to 3 on a scale of 0 to 3) despite concurrent or prior treatment with immunosuppressants such as corticosteroids, azathioprine, or 6-MP in two randomized, double-blind, placebo-controlled clinical studies (Studies UC-I and UC-II). Both studies enrolled TNF-blocker naïve patients, but Study UC-II also allowed entry of patients who lost response to or were intolerant to TNF- blockers. Forty percent (40%) of patients enrolled in Study UC-II had previously used another TNF-blocker. Concomitant stable doses of aminosalicylates and immunosuppressants were permitted. In Studies UC-I and II, patients were receiving aminosalicylates (69%), corticosteroids (59%) and/or azathioprine or 6-MP (37%) at baseline. In both studies, 92% of patients received at least one of these medications. Induction of clinical remission (defined as Mayo score ≤ 2 with no individual subscores > 1) at Week 8 was evaluated in both studies. Clinical remission at Week 52 and sustained clinical remission (defined as clinical remission at both Weeks 8 and 52) were evaluated in Study UC-II. In Study UC-I, 390 TNF-blocker naïve patients were randomized to one of three treatment groups for the primary efficacy analysis. The placebo group received placebo at Weeks 0, 2, 4 and 6. The 160/80 group received 160 mg adalimumab at Week 0 and 80 mg at Week 2, and the 80/40 group received 80 mg adalimumab at Week 0 and 40 mg at Week 2. After Week 2, patients in both adalimumab treatment groups received 40 mg every other week. In Study UC-II, 518 patients were randomized to receive either adalimumab 160 mg at Week 0, 80 mg at Week 2, and 40 mg every other week starting at Week 4 through Week 50, or placebo starting at Week 0 and every other week through Week 50. Corticosteroid taper was permitted starting at Week 8. In both Studies UC-I and UC-II, a greater percentage of the patients treated with 160/80 mg of adalimumab compared to patients treated with placebo achieved induction of clinical remission. In Study UC-II, a greater percentage of the patients treated with 160/80 mg of adalimumab compared to patients treated with placebo achieved sustained clinical remission (clinical remission at both Weeks 8 and 52) ( Table 15 ). Table 15: Induction of Clinical Remission in Studies UC-I and UC-II and Sustained Clinical Remission in Study UC-II (Percent of Patients) Study UC-I Study UC-II Placebo N=130 Adalimumab 160/80 mg N=130 Treatment Difference (95% CI) Placebo N=246 Adalimumab 160/80 mg N=248 Treatment Difference (95% CI) Induction of Clinical 9.2% 18.5% 9.3%* 9.3% 16.5% 7.2%* Remission (Clinical (0.9%, (1.2%, Remission at Week 8) 17.6%) 12.9%) Sustained Clinical Remission (Clinical Remission at both Weeks 8 and 52) N/A N/A N/A 4.1% 8.5% 4.4%* (0.1%, 8.6%) Clinical remission is defined as Mayo score ≤ 2 with no individual subscores > 1. CI=Confidence interval * p<0.05 for adalimumab vs. placebo pairwise comparison of proportions In Study UC-I, there was no statistically significant difference in clinical remission observed between the adalimumab 80/40 mg group and the placebo group at Week 8. In Study UC-II, 17.3% (43/248) in the adalimumab group were in clinical remission at Week 52 compared to 8.5% (21/246) in the placebo group (treatment difference: 8.8%; 95% confidence interval (CI): [2.8%, 14.5%]; p<0.05). In the subgroup of patients in Study UC-II with prior TNF-blocker use, the treatment difference for induction of clinical remission appeared to be lower than that seen in the whole study population, and the treatment differences for sustained clinical remission and clinical remission at Week 52 appeared to be similar to those seen in the whole study population. The subgroup of patients with prior TNF-blocker use achieved induction of clinical remission at 9% (9/98) in the adalimumab group versus 7% (7/101) in the placebo group, and sustained clinical remission at 5% (5/98) in the adalimumab group versus 1% (1/101) in the placebo group. In the subgroup of patients with prior TNF-blocker use, 10% (10/98) were in clinical remission at Week 52 in the adalimumab group versus 3% (3/101) in the placebo group. 14.8 Plaque Psoriasis The safety and efficacy of adalimumab were assessed in randomized, double-blind, placebo- controlled studies in 1696 adult subjects with moderate to severe chronic plaque psoriasis (Ps) who were candidates for systemic therapy or phototherapy. Study Ps-I evaluated 1212 subjects with chronic Ps with ≥10% body surface area (BSA) involvement, Physician’s Global Assessment (PGA) of at least moderate disease severity, and Psoriasis Area and Severity Index (PASI) ≥12 within three treatment periods. In period A, subjects received placebo or adalimumab at an initial dose of 80 mg at Week 0 followed by a dose of 40 mg every other week starting at Week 1. After 16 weeks of therapy, subjects who achieved at least a PASI 75 response at Week 16, defined as a PASI score improvement of at least 75% relative to baseline, entered period B and received open-label 40 mg adalimumab every other week. After 17 weeks of open label therapy, subjects who maintained at least a PASI 75 response at Week 33 and were originally randomized to active therapy in period A were re-randomized in period C to receive 40 mg adalimumab every other week or placebo for an additional 19 weeks. Across all treatment groups the mean baseline PASI score was 19 and the baseline Physician’s Global Assessment score ranged from “moderate” (53%) to “severe” (41%) to “very severe” (6%). Study Ps-II evaluated 99 subjects randomized to adalimumab and 48 subjects randomized to placebo with chronic plaque psoriasis with ≥10% BSA involvement and PASI ≥12. Subjects received placebo, or an initial dose of 80 mg adalimumab at Week 0 followed by 40 mg every other week starting at Week 1 for 16 weeks. Across all treatment groups the mean baseline PASI score was 21 and the baseline PGA score ranged from “moderate” (41%) to “severe” (51%) to “very severe” (8%). Studies Ps-I and II evaluated the proportion of subjects who achieved “clear” or “minimal” disease on the 6-point PGA scale and the proportion of subjects who achieved a reduction in PASI score of at least 75% (PASI 75) from baseline at Week 16 (see Table 16 and 17 ). Additionally, Study Ps-I evaluated the proportion of subjects who maintained a PGA of “clear” or “minimal” disease or a PASI 75 response after Week 33 and on or before Week 52. Table 16: Efficacy Results at 16 Weeks in Study Ps-I Number of Subjects (%) Adalimumab 40 mg every other week Placebo N = 814 N = 398 PGA: Clear or minimal * 506 (62%) 17 (4%) PASI 75 578 (71%) 26 (7%) * Clear = no plaque elevation, no scale, plus or minus hyperpigmentation or diffuse pink or red coloration Minimal = possible but difficult to ascertain whether there is slight elevation of plaque above normal skin, plus or minus surface dryness with some white coloration, plus or minus up to red coloration Table 17: Efficacy Results at 16 Weeks in Study Ps-II Number of Subjects (%) Adalimumab 40 mg every other week Placebo N = 99 N = 48 PGA: Clear or minimal * 70 (71%) 5 (10%) PASI 75 77 (78%) 9 (19%) * Clear = no plaque elevation, no scale, plus or minus hyperpigmentation or diffuse pink or red coloration Minimal = possible but difficult to ascertain whether there is slight elevation of plaque above normal skin, plus or minus surface dryness with some white coloration, plus or minus up to red coloration Additionally, in Study Ps-I, subjects on adalimumab who maintained a PASI 75 were re- randomized to adalimumab (N = 250) or placebo (N = 240) at Week 33. After 52 weeks of treatment with adalimumab, more subjects on adalimumab maintained efficacy when compared to subjects who were re-randomized to placebo based on maintenance of PGA of “clear” or “minimal” disease (68% vs. 28%) or a PASI 75 (79% vs. 43%). A total of 347 stable responders participated in a withdrawal and retreatment evaluation in an open-label extension study. Median time to relapse (decline to PGA “moderate” or worse) was approximately 5 months. During the withdrawal period, no subject experienced transformation to either pustular or erythrodermic psoriasis. A total of 178 subjects who relapsed re-initiated treatment with 80 mg of adalimumab, then 40 mg every other week beginning at week 1. At week 16, 69% (123/178) of subjects had a response of PGA “clear” or “minimal”. A randomized, double-blind study (Study Ps-III) compared the efficacy and safety of adalimumab versus placebo in 217 adult subjects. Subjects in the study had to have chronic plaque psoriasis of at least moderate severity on the PGA scale, fingernail involvement of at least moderate severity on a 5-point Physician’s Global Assessment of Fingernail Psoriasis (PGA-F) scale, a Modified Nail Psoriasis Severity Index (mNAPSI) score for the target-fingernail of ≥ 8, and either a BSA involvement of at least 10% or a BSA involvement of at least 5% with a total mNAPSI score for all fingernails of ≥ 20. Subjects received an initial dose of 80 mg adalimumab followed by 40 mg every other week (starting one week after the initial dose) or placebo for 26 weeks followed by open-label adalimumab treatment for an additional 26 weeks. This study evaluated the proportion of subjects who achieved “clear” or “minimal” assessment with at least a 2-grade improvement on the PGA-F scale and the proportion of subjects who achieved at least a 75% improvement from baseline in the mNAPSI score (mNAPSI 75) at Week 26. At Week 26, a higher proportion of subjects in the adalimumab group than in the placebo group achieved the PGA-F endpoint. Furthermore, a higher proportion of subjects in the adalimumab group than in the placebo group achieved mNAPSI 75 at Week 26 (see Table 18 ). Table 18: Efficacy Results at 26 Weeks Endpoint Adalimumab 40 mg every other week* N=109 Placebo N=108 PGA-F: ≥2-grade improvement and clear or minimal 49% 7% mNAPSI 75 47% 3% *Subjects received 80 mg of adalimumab at Week 0, followed by 40 mg every other week starting at Week 1. Nail pain was also evaluated and improvement in nail pain was observed in Study Ps-III. 14.9 Hidradenitis Suppurativa Two randomized, double-blind, placebo-controlled studies (Studies HS-I and II) evaluated the safety and efficacy of adalimumab in a total of 633 adult subjects with moderate to severe hidradenitis suppurativa (HS) with Hurley Stage II or III disease and with at least 3 abscesses or inflammatory nodules. In both studies, subjects received placebo or adalimumab at an initial dose of 160 mg at Week 0, 80 mg at Week 2, and 40 mg every week starting at Week 4 and continued through Week 11. Subjects used topical antiseptic wash daily. Concomitant oral antibiotic use was allowed in Study HS-II. Both studies evaluated Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 12. HiSCR was defined as at least a 50% reduction in total abscess and inflammatory nodule count with no increase in abscess count and no increase in draining fistula count relative to baseline (see Table 18). Reduction in HS-related skin pain was assessed using a Numeric Rating Scale in patients who entered the study with an initial baseline score of 3 or greater on a 11 point scale. In both studies, a higher proportion of adalimumab- than placebo-treated subjects achieved HiSCR (see Table 19 ). Table 19: Efficacy Results at 12 Weeks in Subjects with Moderate to Severe Hidradenitis Suppurativa HS Study I HS Study II* Placebo Adalimumab 40 mg Weekly Placebo Adalimumab 40 mg Weekly Hidradenitis Suppurativa Clinical Response (HiSCR) N = 154 40 (26%) N = 153 64 (42%) N=163 45 (28%) N=163 96 (59%) *19.3% of subjects in Study HS-II continued baseline oral antibiotic therapy during the study. In both studies, from Week 12 to Week 35 (Period B), subjects who had received adalimumab were re-randomized to 1 of 3 treatment groups (adalimumab 40 mg every week, adalimumab 40 mg every other week, or placebo). Subjects who had been randomized to placebo were assigned to receive adalimumab 40 mg every week (Study HS-I) or placebo (Study HS-II). During Period B, flare of HS, defined as ≥25% increase from baseline in abscesses and inflammatory nodule counts and with a minimum of 2 additional lesions, was documented in 22 (22%) of the 100 subjects who were withdrawn from adalimumab treatment following the primary efficacy timepoint in two studies. 14.10 Adult Uveitis The safety and efficacy of adalimumab were assessed in adult patients with non-infectious intermediate, posterior and panuveitis excluding patients with isolated anterior uveitis, in two randomized, double-masked, placebo-controlled studies (UV I and II). Patients received placebo or adalimumab at an initial dose of 80 mg followed by 40 mg every other week starting one week after the initial dose. The primary efficacy endpoint in both studies was ´time to treatment failure´. Treatment failure was a multi-component outcome defined as the development of new inflammatory chorioretinal and/or inflammatory retinal vascular lesions, an increase in anterior chamber (AC) cell grade or vitreous haze (VH) grade or a decrease in best corrected visual acuity (BCVA). Study UV I evaluated 217 patients with active uveitis while being treated with corticosteroids (oral prednisone at a dose of 10 to 60 mg/day). All patients received a standardized dose of prednisone 60 mg/day at study entry followed by a mandatory taper schedule, with complete corticosteroid discontinuation by Week 15. Study UV II evaluated 226 patients with inactive uveitis while being treated with corticosteroids (oral prednisone 10 to 35 mg/day) at baseline to control their disease. Patients subsequently underwent a mandatory taper schedule, with complete corticosteroid discontinuation by Week 19. Clinical Response Results from both studies demonstrated statistically significant reduction of the risk of treatment failure in patients treated with adalimumab versus patients receiving placebo. In both studies, all components of the primary endpoint contributed cumulatively to the overall difference between adalimumab and placebo groups ( Table 20 ). Table 20: Time to Treatment Failure in Studies UV I and UV II Placebo (N = 107) ADALIMUMAB (N = 110) HR [95% CI] a Placebo (N = 111) ADALIMUMAB (N = 115) HR [95% CI] a Failure b n (%) 84 (78.5) 60 (54.5) 0.50 [0.36, 0.70] 61 (55.0) 45 (39.1) 0.57 [0.39, 0.84] Median Time to Failure (Months) [95% CI] 3.0 [2.7, 3.7] 5.6 [3.9, 9.2] N/A 8.3 [4.8, 12.0] NE c N/A a HR of adalimumab versus placebo from proportional hazards regression with treatment as factor. b Treatment failure at or after Week 6 in Study UV I, or at or after Week 2 in Study UV II, was counted as event. Subjects who discontinued the study were censored at the time of dropping out. c NE = not estimable. Fewer than half of at-risk subjects had an event. Figure 3: Kaplan-Meier Curves Summarizing Time to Treatment Failure on or after Week 6 (Study UV I) or Week 2 (Study UV II) Study UV I Study UV II Note: P# = Placebo (Number of Events/Number at Risk); A# = adalimumab (Number of Events/Number at Risk). adali-graph-03.jpg adali-graph-04.jpg"],"pharmacodynamics":["12.2 Pharmacodynamics After treatment with adalimumab, a decrease in concentrations of acute phase reactants of inflammation (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) and serum cytokines (IL-6) was observed compared to baseline in patients with rheumatoid arthritis. A decrease in CRP concentrations was also observed in patients with Crohn’s disease, ulcerative colitis and hidradenitis suppurativa. Serum concentrations of matrix metalloproteinases (MMP-1 and MMP-3) that produce tissue remodeling responsible for cartilage destruction were also decreased after adalimumab administration."],"pharmacokinetics":["12.3 Pharmacokinetics The pharmacokinetics of adalimumab were linear over the dose range of 0.5 to 10 mg/kg following administration of a single intravenous dose (adalimumab products are not approved for intravenous use). Following 20, 40, and 80 mg every other week and every week subcutaneous administration, adalimumab mean serum trough concentrations at steady state increased approximately proportionally with dose in RA patients. The mean terminal half-life was approximately 2 weeks, ranging from 10 to 20 days across studies. Healthy subjects and patients with RA displayed similar adalimumab pharmacokinetics. Adalimumab exposure in patients treated with 80 mg every other week is estimated to be comparable with that in patients treated with 40 mg every week. Absorption The average absolute bioavailability of adalimumab following a single 40 mg subcutaneous dose was 64%. The mean time to reach the maximum concentration was 5.5 days (131 ± 56 hours) and the maximum serum concentration was 4.7 ± 1.6 mcg/mL in healthy subjects following a single 40 mg subcutaneous administration of adalimumab. Distribution The distribution volume (V ss ) ranged from 4.7 to 6.0 L following intravenous administration of doses ranging from 0.25 to 10 mg/kg in RA patients. Elimination The single dose pharmacokinetics of adalimumab in RA patients were determined in several studies with intravenous doses ranging from 0.25 to 10 mg/kg. The systemic clearance of adalimumab is approximately 12 mL/hr. In long-term studies with dosing more than two years, there was no evidence of changes in clearance over time in RA patients. Patient Population Rheumatoid Arthritis and Ankylosing Spondylitis: In patients receiving 40 mg adalimumab every other week, adalimumab mean steady-state trough concentrations were approximately 5 mcg/mL and 8 to 9 mcg/mL, without and with MTX concomitant treatment, respectively. Adalimumab concentrations in the synovial fluid from five rheumatoid arthritis patients ranged from 31 to 96% of those in serum. The pharmacokinetics of adalimumab in patients with AS were similar to those in patients with RA. Psoriatic Arthritis : In patients receiving 40 mg every other week, adalimumab mean steady-state trough concentrations were 6 to 10 mcg/mL and 8.5 to 12 mcg/mL, without and with MTX concomitant treatment, respectively. Plaque Psoriasis : Adalimumab mean steady-state trough concentration was approximately 5 to 6 mcg/mL during adalimumab 40 mg every other week treatment. Adult Uveitis : Adalimumab mean steady concentration was approximately 8 to 10 mcg/mL during adalimumab 40 mg every other week treatment. Adult Hidradenitis Suppurativa : Adalimumab trough concentrations were approximately 7 to 8 mcg/mL at Week 2 and Week 4, respectively, after receiving 160 mg on Week 0 followed by 80 mg on Week 2. Mean steady-state trough concentrations at Week 12 through Week 36 were approximately 7 to 11 mcg/mL during adalimumab 40 mg every week treatment. Adult Crohn’s Disease: Adalimumab mean trough concentrations were approximately 12 mcg/mL at Week 2 and Week 4 after receiving 160 mg on Week 0 followed by 80 mg on Week 2. Mean steady-state trough concentrations were 7 mcg/mL at Week 24 and Week 56 during adalimumab 40 mg every other week treatment. Adult Ulcerative Colitis : Adalimumab mean trough concentrations were approximately 12 mcg/mL at Week 2 and Week 4 after receiving 160 mg on Week 0 followed by 80 mg on Week 2. Mean steady-state trough concentrations were approximately 8 mcg/mL and 15 mcg/mL at Week 52 after receiving a dose of adalimumab 40 mg every other week and 40 mg every week, respectively. Anti-Drug Antibody Effects on Pharmacokinetics Rheumatoid Arthritis: A trend toward higher apparent clearance of adalimumab in the presence of anti-adalimumab antibodies was identified. Hidradenitis Suppurativa: In subjects with moderate to severe HS, antibodies to adalimumab were associated with reduced serum adalimumab concentrations. In general, the extent of reduction in serum adalimumab concentrations is greater with increasing titers of antibodies to adalimumab. Specific Populations Geriatric Patients : A lower clearance with increasing age was observed in patients with RA aged 40 to >75 years. Pediatric Patients: Juvenile Idiopathic Arthritis : • 4 years to 17 years of age: The adalimumab mean steady-state trough concentrations were 6.8 mcg/mL and 10.9 mcg/mL in patients weighing <30 kg receiving 20 mg adalimumab subcutaneously every other week as monotherapy or with concomitant MTX, respectively. The adalimumab mean steady-state trough concentrations were 6.6 mcg/mL and 8.1 mcg/mL in patients weighing ≥30 kg receiving 40 mg adalimumab subcutaneously every other week as monotherapy or with MTX concomitant treatment, respectively. • 2 years to <4 years of age or 4 years of age and older weighing <15 kg: The adalimumab mean steady-state trough adalimumab concentrations were 6.0 mcg/mL and 7.9 mcg/mL in patients receiving adalimumab subcutaneously every other week as monotherapy or with MTX concomitant treatment, respectively. Pediatric Crohn's Disease : Adalimumab mean ± SD concentrations were 15.7±6.5 mcg/mL at Week 4 following 160 mg at Week 0 and 80 mg at Week 2, and 10.5±6.0 mcg/mL at Week 52 following 40 mg every other week dosing in patients weighing ≥ 40 kg. Adalimumab mean ± SD concentrations were 10.6±6.1 mcg/mL at Week 4 following dosing 80 mg at Week 0 and 40 mg at Week 2, and 6.9±3.6 mcg/mL at Week 52 following 20 mg every other week dosing in patients weighing < 40 kg. Male and Female Patients : No gender-related pharmacokinetic differences were observed after correction for a patient’s body weight. Healthy subjects and patients with rheumatoid arthritis displayed similar adalimumab pharmacokinetics. Patients with Renal or Hepatic Impairment: No pharmacokinetic data are available in patients with hepatic or renal impairment. Rheumatoid factor or CRP concentrations: Minor increases in apparent clearance were predicted in RA patients receiving doses lower than the recommended dose and in RA patients with high rheumatoid factor or CRP concentrations. These increases are not likely to be clinically important. Drug Interaction Studies: Methotrexate : MTX reduced adalimumab apparent clearance after single and multiple dosing by 29% and 44% respectively, in patients with RA [see Drug Interactions ( 7.1 )] ."],"adverse_reactions":["6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Serious Infections [see Warnings and Precautions ( 5.1 )] • Malignancies [see Warnings and Precautions ( 5.2 )] • Hypersensitivity Reactions [see Warnings and Precautions ( 5.3 )] • Hepatitis B Virus Reactivation [see Warnings and Precautions ( 5.4 )] • Neurologic Reactions [see Warnings and Precautions ( 5.5 )] • Hematological Reactions [see Warnings and Precautions ( 5.6 )] • Heart Failure [see Warnings and Precautions ( 5.8 )] • Autoimmunity [see Warnings and Precautions ( 5.9 )] Most common adverse reactions (>10%) are infections (e.g. upper respiratory, sinusitis), injection site reactions, headache and rash. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The most common adverse reaction with adalimumab was injection site reactions. In placebo- controlled trials, 20% of patients treated with adalimumab developed injection site reactions (erythema and/or itching, hemorrhage, pain or swelling), compared to 14% of patients receiving placebo. Most injection site reactions were described as mild and generally did not necessitate drug discontinuation. The proportion of patients who discontinued treatment due to adverse reactions during the double-blind, placebo-controlled portion of studies in patients with RA (i.e., Studies RA-I, RA‑ II, RA-III and RA-IV) was 7% for patients taking adalimumab and 4% for placebo-treated patients. The most common adverse reactions leading to discontinuation of adalimumab in these RA studies were clinical flare reaction (0.7%), rash (0.3%) and pneumonia (0.3%). Infections In the controlled portions of the 39 global adalimumab clinical trials in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV, the rate of serious infections was 4.3 per 100 patient-years in 7973 adalimumab-treated patients versus a rate of 2.9 per 100 patient-years in 4848 control-treated patients. Serious infections observed included pneumonia, septic arthritis, prosthetic and post- surgical infections, erysipelas, cellulitis, diverticulitis, and pyelonephritis [see Warnings and Precautions ( 5.1 )] . Tuberculosis and Opportunistic Infections In 52 global controlled and uncontrolled clinical trials in RA, PsA, AS, CD, UC, Ps, HS, and UV that included 24,605 adalimumab-treated patients, the rate of reported active tuberculosis was 0.20 per 100 patient-years and the rate of positive PPD conversion was 0.09 per 100 patient-years. In a subgroup of 10,113 U.S. and Canadian adalimumab-treated patients, the rate of reported active TB was 0.05 per 100 patient-years and the rate of positive PPD conversion was 0.07 per 100 patient-years. These trials included reports of miliary, lymphatic, peritoneal, and pulmonary TB. Most of the TB cases occurred within the first eight months after initiation of therapy and may reflect recrudescence of latent disease. In these global clinical trials, cases of serious opportunistic infections have been reported at an overall rate of 0.05 per 100 patient-years. Some cases of serious opportunistic infections and TB have been fatal [see Warnings and Precautions ( 5.1 )] . Autoantibodies In the rheumatoid arthritis controlled trials, 12% of patients treated with adalimumab and 7% of placebo-treated patients that had negative baseline ANA titers developed positive titers at week 24. Two patients out of 3046 treated with adalimumab developed clinical signs suggestive of new- onset lupus-like syndrome. The patients improved following discontinuation of therapy. No patients developed lupus nephritis or central nervous system symptoms. The impact of long-term treatment with adalimumab products on the development of autoimmune diseases is unknown. Liver Enzyme Elevations There have been reports of severe hepatic reactions including acute liver failure in patients receiving TNF-blockers. In controlled Phase 3 trials of adalimumab (40 mg SC every other week) in patients with RA, PsA, and AS with control period duration ranging from 4 to 104 weeks, ALT elevations ≥ 3 x ULN occurred in 3.5% of adalimumab-treated patients and 1.5% of control- treated patients. Since many of these patients in these trials were also taking medications that cause liver enzyme elevations (e.g., NSAIDS, MTX), the relationship between adalimumab and the liver enzyme elevations is not clear. In a controlled Phase 3 trial of adalimumab in patients with polyarticular JIA who were 4 to 17 years, ALT elevations ≥ 3 x ULN occurred in 4.4% of adalimumab-treated patients and 1.5% of control-treated patients (ALT more common than AST); liver enzyme test elevations were more frequent among those treated with the combination of adalimumab and MTX than those treated with adalimumab alone. In general, these elevations did not lead to discontinuation of adalimumab treatment. No ALT elevations ≥ 3 x ULN occurred in the open-label study of adalimumab in patients with polyarticular JIA who were 2 to <4 years. In controlled Phase 3 trials of adalimumab (initial doses of 160 mg and 80 mg, or 80 mg and 40 mg on Days 1 and 15, respectively, followed by 40 mg every other week) in adult patients with Crohn’s Disease with a control period duration ranging from 4 to 52 weeks, ALT elevations ≥ 3 x ULN occurred in 0.9% of adalimumab-treated patients and 0.9% of control-treated patients. In the Phase 3 trial of adalimumab in pediatric patients with Crohn’s disease which evaluated efficacy and safety of two body weight based maintenance dose regimens following body weight based induction therapy up to 52 weeks of treatment, ALT elevations ≥ 3 x ULN occurred in 2.6% (5/192) of patients, of whom 4 were receiving concomitant immunosuppressants at baseline; none of these patients discontinued due to abnormalities in ALT tests. In controlled Phase 3 trials of adalimumab (initial doses of 160 mg and 80 mg on Days 1 and 15 respectively, followed by 40 mg every other week) in adult patients with UC with control period duration ranging from 1 to 52 weeks, ALT elevations ≥3 x ULN occurred in 1.5% of adalimumab-treated patients and 1.0% of control-treated patients. In controlled Phase 3 trials of adalimumab (initial dose of 80 mg then 40 mg every other week) in patients with Ps with control period duration ranging from 12 to 24 weeks, ALT elevations ≥ 3 x ULN occurred in 1.8% of adalimumab-treated patients and 1.8% of control-treated patients. In controlled trials of adalimumab (initial doses of 160 mg at Week 0 and 80 mg at Week 2, followed by 40 mg every week starting at Week 4), in subjects with HS with a control period duration ranging from 12 to 16 weeks, ALT elevations ≥ 3 x ULN occurred in 0.3% of adalimumab-treated subjects and 0.6% of control-treated subjects. In controlled trials of adalimumab (initial doses of 80 mg at Week 0 followed by 40 mg every other week starting at Week 1) in adult patients with uveitis with an exposure of 165.4 PYs and 119.8 PYs in adalimumab-treated and control-treated patients, respectively, ALT elevations ≥ 3 x ULN occurred in 2.4% of adalimumab-treated patients and 2.4% of control-treated patients. Other Adverse Reactions Rheumatoid Arthritis Clinical Studies The data described below reflect exposure to adalimumab in 2468 patients, including 2073 exposed for 6 months, 1497 exposed for greater than one year and 1380 in adequate and well-controlled studies (Studies RA-I, RA-II, RA-III, and RA-IV). Adalimumab was studied primarily in placebo- controlled trials and in long-term follow up studies for up to 36 months duration. The population had a mean age of 54 years, 77% were female, 91% were Caucasian and had moderately to severely active rheumatoid arthritis. Most patients received 40 mg adalimumab every other week [see Clinical Studies ( 14.1 )]. Table 1 summarizes reactions reported at a rate of at least 5% in patients treated with adalimumab 40 mg every other week compared to placebo and with an incidence higher than placebo. In Study RA-III, the types and frequencies of adverse reactions in the second year open-label extension were similar to those observed in the one-year double-blind portion. Table 1: Adverse Reactions Reported by ≥5% of Patients Treated with Adalimumab during Placebo-Controlled Period of Pooled RA Studies (Studies RA-I, RA-II, RA-III, and RA-IV) Adalimumab 40 mg subcutaneous Every Other Week Placebo (N=705) (N=690) Adverse Reaction (Preferred Term) Respiratory Upper respiratory infection 17% 13% Sinusitis 11% 9% Flu syndrome 7% 6% Gastrointestinal Nausea 9% 8% Abdominal pain 7% 4% Laboratory Tests* Laboratory test abnormal 8% 7% Hypercholesterolemia 6% 4% Hyperlipidemia 7% 5% Hematuria 5% 4% Alkaline phosphatase increased 5% 3% Other Headache 12% 8% Rash 12% 6% Accidental injury 10% 8% Injection site reaction ** 8% 1% Back pain 6% 4% Urinary tract infection 8% 5% Hypertension 5% 3% * Laboratory test abnormalities were reported as adverse reactions in European trials ** Does not include injection site erythema, itching, hemorrhage, pain or swelling Less Common Adverse Reactions in Rheumatoid Arthritis Clinical Studies Other infrequent serious adverse reactions that do not appear in the Warnings and Precautions or Adverse Reaction sections that occurred at an incidence of less than 5% in adalimumab-treated patients in RA studies were: Body As A Whole: Pain in extremity, pelvic pain, surgery, thorax pain Cardiovascular System: Arrhythmia, atrial fibrillation, chest pain, coronary artery disorder, heart arrest, hypertensive encephalopathy, myocardial infarct, palpitation, pericardial effusion, pericarditis, syncope, tachycardia Digestive System: Cholecystitis, cholelithiasis, esophagitis, gastroenteritis, gastrointestinal hemorrhage, hepatic necrosis, vomiting Endocrine System: Parathyroid disorder Hemic And Lymphatic System: Agranulocytosis, polycythemia Metabolic And Nutritional Disorders: Dehydration, healing abnormal, ketosis, paraproteinemia, peripheral edema Musculo-Skeletal System: Arthritis, bone disorder, bone fracture (not spontaneous), bone necrosis, joint disorder, muscle cramps, myasthenia, pyogenic arthritis, synovitis, tendon disorder Neoplasia: Adenoma Nervous System: Confusion, paresthesia, subdural hematoma, tremor Respiratory System: Asthma, bronchospasm, dyspnea, lung function decreased, pleural effusion Special Senses: Cataract Thrombosis: Thrombosis leg Urogenital System: Cystitis, kidney calculus, menstrual disorder Juvenile Idiopathic Arthritis Clinical Studies In general, the adverse reactions in the adalimumab-treated patients in the polyarticular juvenile idiopathic arthritis (JIA) trials (Studies JIA-I and JIA-II) [ see Clinical Studies ( 14.2 )] were similar in frequency and type to those seen in adult patients [see Warnings and Precautions ( 5 ), Adverse Reactions ( 6 )] . Important findings and differences from adults are discussed in the following paragraphs. In Study JIA-I, adalimumab was studied in 171 patients who were 4 to 17 years of age, with polyarticular JIA. Severe adverse reactions reported in the study included neutropenia, streptococcal pharyngitis, increased aminotransferases, herpes zoster, myositis, metrorrhagia, and appendicitis. Serious infections were observed in 4% of patients within approximately 2 years of initiation of treatment with adalimumab and included cases of herpes simplex, pneumonia, urinary tract infection, pharyngitis, and herpes zoster. In Study JIA-I, 45% of patients experienced an infection while receiving adalimumab with or without concomitant MTX in the first 16 weeks of treatment. The types of infections reported in adalimumab-treated patients were generally similar to those commonly seen in polyarticular JIA patients who are not treated with TNF blockers. Upon initiation of treatment, the most common adverse reactions occurring in this patient population treated with adalimumab were injection site pain and injection site reaction (19% and 16%, respectively). A less commonly reported adverse event in patients receiving adalimumab was granuloma annulare which did not lead to discontinuation of adalimumab treatment. In the first 48 weeks of treatment in Study JIA-I, non-serious hypersensitivity reactions were seen in approximately 6% of patients and included primarily localized allergic hypersensitivity reactions and allergic rash. In Study JIA-I, 10% of patients treated with adalimumab who had negative baseline anti-dsDNA antibodies developed positive titers after 48 weeks of treatment. No patient developed clinical signs of autoimmunity during the clinical trial. Approximately 15% of patients treated with adalimumab developed mild-to-moderate elevations of creatine phosphokinase (CPK) in Study JIA-I. Elevations exceeding 5 times the upper limit of normal were observed in several patients. CPK concentrations decreased or returned to normal in all patients. Most patients were able to continue adalimumab without interruption. In Study JIA-II, adalimumab was studied in 32 patients who were 2 to <4 years of age or 4 years of age and older weighing <15 kg with polyarticular JIA. The safety profile for this patient population was similar to the safety profile seen in patients 4 to 17 years of age with polyarticular JIA. In Study JIA-II, 78% of patients experienced an infection while receiving adalimumab. These included nasopharyngitis, bronchitis, upper respiratory tract infection, otitis media, and were mostly mild to moderate in severity. Serious infections were observed in 9% of patients receiving adalimumab in the study and included dental caries, rotavirus gastroenteritis, and varicella. In Study JIA-II, non-serious allergic reactions were observed in 6% of patients and included intermittent urticaria and rash, which were all mild in severity. Psoriatic Arthritis and Ankylosing Spondylitis Clinical Studies Adalimumab has been studied in 395 patients with psoriatic arthritis (PsA) in two placebo- controlled trials and in an open label study and in 393 patients with ankylosing spondylitis (AS) in two placebo-controlled studies [ see Clinical Studies ( 14.3 , 14.4 )] . The safety profile for patients with PsA and AS treated with adalimumab 40 mg every other week was similar to the safety profile seen in patients with RA, adalimumab Studies RA-I through IV. Crohn’s Disease Clinical Studies Adults: The safety profile of adalimumab in 1478 adult patients with Crohn’s disease from four placebo-controlled and two open-label extension studies [see Clinical Studies ( 14.5 )] was similar to the safety profile seen in patients with RA. Pediatric Patients 6 Years to 17 Years : The safety profile of adalimumab in 192 pediatric patients from one double-blind study (Study PCD-I) and one open-label extension study [see Clinical Studies ( 14.6 )] was similar to the safety profile seen in adult patients with Crohn’s disease. During the 4-week open label induction phase of Study PCD-I, the most common adverse reactions occurring in the pediatric population treated with adalimumab were injection site pain and injection site reaction (6% and 5%, respectively). A total of 67% of children experienced an infection while receiving adalimumab in Study PCD-I. These included upper respiratory tract infection and nasopharyngitis. A total of 5% of children experienced a serious infection while receiving adalimumab in Study PCD-I. These included viral infection, device related sepsis (catheter), gastroenteritis, H1N1 influenza, and disseminated histoplasmosis. In Study PCD-I, allergic reactions were observed in 5% of children which were all non-serious and were primarily localized reactions. Ulcerative Colitis Clinical Studies Adults: The safety profile of adalimumab in 1010 adult patients with ulcerative colitis (UC) from two placebo-controlled studies and one open-label extension study [ see Clinical Studies ( 14.7 )] was similar to the safety profile seen in patients with RA. Plaque Psoriasis Clinical Studies Adalimumab has been studied in 1696 subjects with plaque psoriasis (Ps) in placebo-controlled and open-label extension studies [see Clinical Studies ( 14.8 )] . The safety profile for subjects with Ps treated with adalimumab was similar to the safety profile seen in subjects with RA with the following exceptions. In the placebo-controlled portions of the clinical trials in Ps subjects, adalimumab-treated subjects had a higher incidence of arthralgia when compared to controls (3% vs. 1%). Hidradenitis Suppurativa Clinical Studies Adalimumab has been studied in 727 subjects with hidradenitis suppurativa (HS) in three placebo- controlled studies and one open-label extension study [see Clinical Studies ( 14.9 )] . The safety profile for subjects with HS treated with adalimumab weekly was consistent with the known safety profile of adalimumab. Flare of HS, defined as ≥25% increase from baseline in abscesses and inflammatory nodule counts and with a minimum of 2 additional lesions, was documented in 22 (22%) of the 100 subjects who were withdrawn from adalimumab treatment following the primary efficacy timepoint in two studies. Uveitis Clinical Studies Adalimumab has been studied in 464 adult patients with uveitis (UV) in placebo-controlled and open-label extension studies (Study PUV-I) [ see Clinical Studies ( 14.10 ) ]. The safety profile for patients with UV treated with adalimumab was similar to the safety profile seen in patients with RA. 6.2 Immunogenicity The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of adalimumab or of other adalimumab products. There are two assays that have been used to measure anti-adalimumab antibodies. With the ELISA, antibodies to adalimumab could be detected only when serum adalimumab concentrations were < 2 mcg/mL. The ECL assay can detect anti-adalimumab antibody titers independent of adalimumab concentrations in the serum samples. The incidence of anti‑adalimumab antibody (AAA) development in patients treated with adalimumab are presented in Table 2 . Table 2: Anti-Adalimumab Antibody Development Determined by ELISA and ECL Assay in Patients Treated with adalimumab Indications Study Duration Anti-Adalimumab Antibody Incidence by ELISA (n/N) Anti-Adalimumab Antibody Incidence by ECL Assay (n/N) In all patients who received adalimumab In patients with serum adalimumab concentrations < 2 mcg/mL Rheumatoid Arthritis a 6 to 12 months 5% (58/1062) NR NA Juvenile Idiopathic Arthritis (JIA) 4 to 17 years of age b 48 weeks 16% (27/171) NR NA 2 to 4 years of age or ≥ 4 years of age and weighing < 15 kg 24 weeks 7% (1/15) c NR NA Psoriatic Arthritis d 48 weeks e 13% (24/178) NR NA Ankylosing Spondylitis 24 weeks 9% (16/185) NR NA Adult Crohn’s Disease 56 weeks 3% (7/269) 8% (7/86) NA Pediatric Crohn’s Disease 52 weeks 3% (6/182) 10% (6/58) NA Adult Ulcerative Colitis 52 weeks 5% (19/360) 21% (19/92) NA Plaque Psoriasis f Up to 52 weeks g 8% (77/920) 21% (77/372) NA Hidradenitis Suppurativa 36 weeks 7% (30/461) 28% (58/207) h 61% (272/445) i Non-infectious Uveitis 52 weeks 5% (12/249) 21% (12/57) 40% (99/249) j n: number of patients with anti-adalimumab antibody; NR: not reported; NA: Not applicable (not performed) a In patients receiving concomitant methotrexate (MTX), the incidence of anti-adalimumab antibody was 1% compared to 12% with adalimumab monotherapy b In patients receiving concomitant MTX, the incidence of anti-adalimumab antibody was 6% compared to 26% with adalimumab monotherapy c This patient received concomitant MTX d In patients receiving concomitant MTX, the incidence of antibody development was 7% compared to 1% in RA e Subjects enrolled after completing 2 previous studies of 24 weeks or 12 weeks of treatments. f In plaque psoriasis patients who were on adalimumab monotherapy and subsequently withdrawn from the treatment, the rate of antibodies to adalimumab after retreatment was similar to the rate observed prior to withdrawal g One 12-week Phase 2 study and one 52-week Phase 3 study h Among subjects in the 2 Phase 3 studies who stopped adalimumab treatment for up to 24 weeks and in whom adalimumab serum levels subsequently declined to <2 mcg/mL (approximately 22% of total subjects studied) i No apparent association between antibody development and safety was observed j No correlation of antibody development to safety or efficacy outcomes was observed Rheumatoid Arthritis and Psoriatic Arthritis: Patients in Studies RA-I, RA-II, and RA-III were tested at multiple time points for antibodies to adalimumab using the ELISA during the 6- to 12-month period. No apparent correlation of antibody development to adverse reactions was observed. With monotherapy, patients receiving every other week dosing may develop antibodies more frequently than those receiving weekly dosing. In patients receiving the recommended dosage of 40 mg every other week as monotherapy, the ACR 20 response was lower among antibody-positive patients than among antibody-negative patients. The long-term immunogenicity of adalimumab products is unknown. 6.3 Postmarketing Experience The following adverse reactions have been identified during post-approval use of adalimumab products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to adalimumab products exposure. Gastrointestinal disorders: Diverticulitis, large bowel perforations including perforations associated with diverticulitis and appendiceal perforations associated with appendicitis, pancreatitis General disorders and administration site conditions: Pyrexia Hepato-biliary disorders: Liver failure, hepatitis Immune system disorders: Sarcoidosis Neoplasms benign, malignant and unspecified (including cysts and polyps): Merkel Cell Carcinoma (neuroendocrine carcinoma of the skin) Nervous system disorders: Demyelinating disorders (e.g., optic neuritis, Guillain-Barré syndrome), cerebrovascular accident Respiratory disorders: Interstitial lung disease, including pulmonary fibrosis, pulmonary embolism Skin reactions: Stevens Johnson Syndrome, cutaneous vasculitis, erythema multiforme, new or worsening psoriasis (all sub-types including pustular and palmoplantar), alopecia, lichenoid skin reaction Vascular disorders: Systemic vasculitis, deep vein thrombosis"],"contraindications":["4 CONTRAINDICATIONS None. None."],"drug_interactions":["7 DRUG INTERACTIONS • Abatacept: Increased risk of serious infection. ( 5.1 , 5.11 , 7.2 ) • Anakinra: Increased risk of serious infection. ( 5.1 , 5.7 , 7.2 ) • Live vaccines: Avoid use with IDACIO. ( 5.10 , 7.3 ) 7.1 Methotrexate Adalimumab has been studied in rheumatoid arthritis (RA) patients taking concomitant methotrexate (MTX). Although MTX reduced the apparent adalimumab clearance, the data do not suggest the need for dose adjustment of either IDACIO or MTX [see Clinical Pharmacology ( 12.3 )] . 7.2 Biological Products In clinical studies in patients with RA, an increased risk of serious infections has been observed with the combination of TNF blockers with anakinra or abatacept, with no added benefit; therefore, use of IDACIO with abatacept or anakinra is not recommended in patients with RA [see Warnings and Precautions ( 5.7 , 5.11 )] . A higher rate of serious infections has also been observed in patients with RA treated with rituximab who received subsequent treatment with a TNF blocker. There is insufficient information regarding the concomitant use of IDACIO and other biologic products for the treatment of RA, PsA, AS, CD, UC, Ps, HS and UV. Concomitant administration of IDACIO with other biologic DMARDS (e.g., anakinra and abatacept) or other TNF blockers is not recommended based upon the possible increased risk for infections and other potential pharmacological interactions. 7.3 Live Vaccines Avoid the use of live vaccines with IDACIO [see Warnings and Precautions ( 5.10 )] . 7.4 Cytochrome P450 Substrates The formation of CYP450 enzymes may be suppressed by increased concentrations of cytokines (e.g., TNFα, IL-6) during chronic inflammation. It is possible for products that antagonize cytokine activity, such as adalimumab products, to influence the formation of CYP450 enzymes. Upon initiation or discontinuation of IDACIO in patients being treated with CYP450 substrates with a narrow therapeutic index, monitoring of the effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) is recommended and the individual dose of the drug product may be adjusted as needed."],"spl_medguide_table":["<table width=\"100%\" styleCode=\"Noautorules\"><col width=\"50%\"/><col width=\"50%\"/><tbody><tr><td colspan=\"2\" align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">MEDICATION GUIDE  IDACIO&#xAE; (i-DAS-i-oh)  (adalimumab-aacf)  injection, for subcutaneous use</content></paragraph></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph>Read the Medication Guide that comes with IDACIO before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking with your healthcare provider about your medical condition or treatment.</paragraph></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph ID=\"whatisthe\"><content styleCode=\"bold\">What is the most important information I should know about IDACIO? </content></paragraph><paragraph>IDACIO is a medicine that affects your immune system. IDACIO can lower the ability of your immune system to fight infections. <content styleCode=\"bold\">Serious infections have happened in people taking adalimumab products. These serious infections include tuberculosis (TB) and infections caused by viruses, fungi or bacteria that have spread throughout the body. Some people have died from these infections.</content></paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption>Your healthcare provider should test you for TB before starting IDACIO.</item><item><caption>&#x2022;</caption>Your healthcare provider should check you closely for signs and symptoms of TB during treatment with IDACIO.</item></list><paragraph>You should not start taking IDACIO if you have any kind of infection unless your healthcare provider says it is okay.</paragraph><paragraph><content styleCode=\"bold\">Before starting IDACIO, tell your healthcare provider if you: </content></paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption>think you have an infection or have symptoms of an infection such as: </item></list></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><list listType=\"unordered\"><item><caption>o</caption>fever, sweats, or chills</item><item><caption>o</caption>muscle aches</item><item><caption>o</caption>cough</item><item><caption>o</caption>shortness of breath</item><item><caption>o</caption>blood in phlegm</item><item><caption>o</caption>warm, red, or painful skin or sores on your body</item></list></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><list listType=\"unordered\"><item><caption>o</caption>diarrhea or stomach pain</item><item><caption>o</caption>burning when you urinate or urinate more often than normal</item><item><caption>o</caption>feel very tired</item><item><caption>o</caption>weight loss</item></list></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><list listType=\"unordered\"><item><caption>&#x2022;</caption>are being treated for an infection.</item><item><caption>&#x2022;</caption>get a lot of infections or have infections that keep coming back. </item><item><caption>&#x2022;</caption>have diabetes</item><item><caption>&#x2022;</caption>have TB or have been in close contact with someone with TB.</item><item><caption>&#x2022;</caption>were born in, lived in, or traveled to countries where there is more risk for getting TB. Ask your healthcare provider if you are not sure.</item><item><caption>&#x2022;</caption>live or have lived in certain parts of the country (such as the Ohio and Mississippi River valleys) where there is an increased risk for getting certain kinds of fungal infections (histoplasmosis, coccidioidomycosis, or blastomycosis). These infections may happen or become more severe if you use IDACIO. Ask your healthcare provider if you do not know if you have lived in an area where these infections are common.</item><item><caption>&#x2022;</caption>have or have had hepatitis B</item><item><caption>&#x2022;</caption>use the medicine ORENCIA (abatacept), KINERET (anakinra), RITUXAN (rituximab), IMURAN (azathioprine), or PURINETHOL (6&#x2013;mercaptopurine, 6-MP).</item><item><caption>&#x2022;</caption>are scheduled to have major surgery.</item></list><paragraph><content styleCode=\"bold\">After starting IDACIO, call your healthcare provider right away</content> if you have an infection, or any sign of an infection. </paragraph><paragraph>IDACIO can make you more likely to get infections or make any infection that you may have worse.</paragraph><paragraph><content styleCode=\"bold\">Cancer</content></paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption>For children and adults taking Tumor Necrosis Factor (TNF)-blockers, including IDACIO, the chances of getting cancer may increase.</item><item><caption>&#x2022;</caption>There have been cases of unusual cancers in children, teenagers, and young adults using TNF-blockers.</item><item><caption>&#x2022;</caption>People with rheumatoid arthritis (RA), especially more serious RA, may have a higher chance for getting a kind of cancer called lymphoma.</item><item><caption>&#x2022;</caption>If you use TNF blockers including IDACIO your chance of getting two types of skin cancer may increase (basal cell cancer and squamous cell cancer of the skin). These types of cancer are generally not life-threatening if treated. Tell your healthcare provider if you have a bump or open sore that does not heal.</item><item><caption>&#x2022;</caption>Some people receiving TNF blockers including IDACIO developed a rare type of cancer called hepatosplenic T-cell lymphoma. This type of cancer often results in death. Most of these people were male teenagers or young men. Also, most people were being treated for Crohn&#x2019;s disease or ulcerative colitis with another medicine called IMURAN (azathioprine) or PURINETHOL (6-mercaptopurine, 6&#x2013;MP).</item></list></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"bold\">What is IDACIO?</content></paragraph><paragraph>IDACIO is a medicine called a Tumor Necrosis Factor (TNF) blocker. IDACIO is used: </paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption>To reduce the signs and symptoms of: <list listType=\"unordered\"><item><caption>o</caption><content styleCode=\"bold\">moderate to severe RA in adults. </content>IDACIO can be used alone, with methotrexate, or with certain other medicines.</item><item><caption>o</caption><content styleCode=\"bold\">moderate to severe polyarticular juvenile idiopathic arthritis (JIA) in children</content> 2 years and older. IDACIO can be used alone, or with methotrexate.</item><item><caption>o</caption><content styleCode=\"bold\">psoriatic arthritis (PsA) in adults.</content> IDACIO can be used alone or with certain other medicines.</item><item><caption>o</caption><content styleCode=\"bold\">ankylosing spondylitis (AS) in adults.</content></item><item><caption>o</caption><content styleCode=\"bold\">moderate to severe hidradenitis suppurativa (HS) in adults.</content></item></list></item><item><caption>&#x2022;</caption><content styleCode=\"bold\">To treat moderate to severe Crohn&#x2019;s disease (CD) in adults and children 6 years of age and older.</content></item><item><caption>&#x2022;</caption><content styleCode=\"bold\">To treat moderate to severe ulcerative colitis (UC) in adults.</content> It is not known if adalimumab products are effective in people who stopped responding to or could not tolerate TNF-blocker medicines.</item><item><caption>&#x2022;</caption><content styleCode=\"bold\">To treat moderate to severe chronic (lasting a long time) plaque psoriasis (Ps) in adults </content>who have the condition in many areas of their body and who may benefit from taking injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet light alone or with pills).</item><item><caption>&#x2022;</caption><content styleCode=\"bold\">To treat non-infectious intermediate, posterior, and panuveitis in adults.</content></item></list></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"bold\">What should I tell my healthcare provider before taking IDACIO? </content></paragraph><paragraph>IDACIO may not be right for you. Before starting IDACIO, tell your healthcare provider about all of your medical conditions, including if you: </paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption>have an infection. See <content styleCode=\"bold\">&#x201C;<linkHtml href=\"#whatisthe\">What is the most important information I should know about IDACIO?</linkHtml>&#x201D;</content></item><item><caption>&#x2022;</caption>have or have had cancer.</item><item><caption>&#x2022;</caption>have any numbness or tingling or have a disease that affects your nervous system such as multiple sclerosis or Guillain-Barr&#xE9; syndrome.</item><item><caption>&#x2022;</caption>have or had heart failure.</item><item><caption>&#x2022;</caption>have recently received or are scheduled to receive a vaccine. You may receive vaccines, except for live vaccines while using IDACIO. Children should be brought up to date with all vaccines before starting IDACIO.</item><item><caption>&#x2022;</caption>are allergic to IDACIO or to any of its ingredients. See the end of this Medication Guide for a list of ingredients in IDACIO.</item><item><caption>&#x2022;</caption>are pregnant or plan to become pregnant, breastfeeding or plan to breastfeed. You and your healthcare provider should decide if you should take IDACIO while you are pregnant or breastfeeding.</item><item><caption>&#x2022;</caption>have a baby and you were using IDACIO during your pregnancy. Tell your baby&#x2019;s healthcare provider before your baby receives any vaccines.</item></list><paragraph><content styleCode=\"bold\">Tell your healthcare provider about all the medicines you take,</content> including prescription and over-the-counter medicines, vitamins, and herbal supplements. </paragraph><paragraph><content styleCode=\"bold\">Especially tell your healthcare provider if you use: </content></paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption>ORENCIA (abatacept), KINERET (anakinra), REMICADE (infliximab), ENBREL (etanercept), CIMZIA (certolizumab pegol) or SIMPONI (golimumab), because you should not use IDACIO while you are also using one of these medicines.</item><item><caption>&#x2022;</caption>RITUXAN (rituximab). Your healthcare provider may not want to give you IDACIO if you have received RITUXAN (rituximab) recently.</item><item><caption>&#x2022;</caption>IMURAN (azathioprine) or PURINETHOL (6&#x2013;mercaptopurine, 6-MP).</item></list><paragraph><content styleCode=\"bold\">Keep a list of your medicines with you to show your healthcare provider and pharmacist each time you get a new medicine.</content></paragraph></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"bold\">How should I take IDACIO? </content></paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption>IDACIO is given by an injection under the skin. Your healthcare provider will tell you how often to take an injection of IDACIO. This is based on your condition to be treated. <content styleCode=\"bold\">Do not inject IDACIO more often than you were prescribed.</content></item><item><caption>&#x2022;</caption>See the <content styleCode=\"bold\"><linkHtml href=\"#Instructions\">Instructions for Use</linkHtml></content> inside the carton for complete instructions for the right way to prepare and inject IDACIO.</item><item><caption>&#x2022;</caption>Make sure you have been shown how to inject IDACIO before you do it yourself. If you have any questions about giving yourself an injection, you can call your healthcare provider or the patient support program at 1-833-522-4227. Someone you know can also help you with your injection after they have been shown how to prepare and inject IDACIO.</item><item><caption>&#x2022;</caption><content styleCode=\"bold\">Do not </content>try to inject IDACIO yourself until you have been shown the right way to give the injections. If your healthcare provider decides that you or a caregiver may be able to give your injections of IDACIO at home, you should receive training on the right way to prepare and inject IDACIO.</item><item><caption>&#x2022;</caption>Do not miss any doses of IDACIO unless your healthcare provider says it is okay. If you forget to take IDACIO, inject a dose as soon as you remember. Then, take your next dose at your regular scheduled time. This will put you back on schedule. In case you are not sure when to inject IDACIO, call your healthcare provider or pharmacist.</item><item><caption>&#x2022;</caption>If you take more IDACIO than you were told to take, call your healthcare provider.</item></list></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"bold\">What are the possible side effects of IDACIO? </content></paragraph><paragraph>IDACIO can cause serious side effects, including: </paragraph><paragraph><content styleCode=\"bold\">See &#x201C;What is the most important information I should know about IDACIO?&#x201D;</content></paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption><content styleCode=\"bold\">Serious Infections.</content></item></list><paragraph>Your healthcare provider will examine you for TB and perform a test to see if you have TB. If your healthcare provider feels that you are at risk for TB, you may be treated with medicine for TB before you begin treatment with IDACIO and during treatment with IDACIO. Even if your TB test is negative your healthcare provider should carefully monitor you for TB infections while you are taking IDACIO. People who had a negative TB skin test before receiving adalimumab products have developed active TB. Tell your healthcare provider if you have any of the following symptoms while taking or after taking IDACIO:</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><list listType=\"unordered\"><item><caption>o</caption>cough that does not go away</item><item><caption>o</caption>weight loss</item></list></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><list listType=\"unordered\"><item><caption>o</caption>low grade fever</item><item><caption>o</caption>loss of body fat and muscle (wasting)</item></list></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><list listType=\"unordered\"><item><caption>&#x2022;</caption><content styleCode=\"bold\">Hepatitis B infection in people who carry the virus in their blood. </content></item></list><paragraph>If you are a carrier of the hepatitis B virus (a virus that affects the liver), the virus can become active while you use IDACIO. Your healthcare provider should do blood tests before you start treatment, while you are using IDACIO, and for several months after you stop treatment with IDACIO. Tell your healthcare provider if you have any of the following symptoms of a possible hepatitis B infection:</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><list listType=\"unordered\"><item><caption>o</caption>muscle aches</item><item><caption>o</caption>feel very tired</item><item><caption>o</caption>dark urine</item><item><caption>o</caption>skin or eyes look yellow</item><item><caption>o</caption>little or no appetite</item><item><caption>o</caption>vomiting</item></list></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><list listType=\"unordered\"><item><caption>o</caption>clay-colored bowel movements</item><item><caption>o</caption>fever</item><item><caption>o</caption>chills</item><item><caption>o</caption>stomach discomfort</item><item><caption>o</caption>skin rash</item></list></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><list listType=\"unordered\"><item><caption>&#x2022;</caption><content styleCode=\"bold\">Allergic reactions. </content>Allergic reactions can happen in people who use IDACIO. Call your healthcare provider or get medical help right away if you have any of these symptoms of a serious allergic reaction:</item></list></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><list listType=\"unordered\"><item><caption>o</caption>Hives</item><item><caption>o</caption>trouble breathing</item></list></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><list listType=\"unordered\"><item><caption>o</caption>swelling of your face, eyes, lips or mouth</item></list></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><list listType=\"unordered\"><item><caption>&#x2022;</caption><content styleCode=\"bold\">Nervous system problems. </content>Signs and symptoms of a nervous system problem include numbness or tingling, problems with your vision, weakness in your arms or legs, and dizziness.</item><item><caption>&#x2022;</caption><content styleCode=\"bold\">Blood problems. </content>Your body may not make enough of the blood cells that help fight infections or help to stop bleeding. Symptoms include a fever that does not go away, bruising or bleeding very easily, or looking very pale.</item><item><caption>&#x2022;</caption><content styleCode=\"bold\">New heart failure or worsening of heart failure you already have. Call your healthcare provider right away </content>if you get new worsening symptoms of heart failure while taking IDACIO, including:</item></list></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><list listType=\"unordered\"><item><caption>o</caption>shortness of breath</item><item><caption>o</caption>sudden weight gain</item></list></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><list listType=\"unordered\"><item><caption>o</caption>swelling of your ankles or feet</item></list></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><list listType=\"unordered\"><item><caption>&#x2022;</caption><content styleCode=\"bold\">Immune reactions including a lupus-like syndrome. </content>Symptoms include chest discomfort or pain that does not go away, shortness of breath, joint pain, or a rash on your cheeks or arms that gets worse in the sun. Symptoms may improve when you stop IDACIO.</item><item><caption>&#x2022;</caption><content styleCode=\"bold\">Liver Problems. </content>Liver problems can happen in people who use TNF-blocker medicines. These problems can lead to liver failure and death. Call your healthcare provider right away if you have any of these symptoms: </item></list></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><list listType=\"unordered\"><item><caption>o</caption>feel very tired</item><item><caption>o</caption>poor appetite or vomiting</item></list></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><list listType=\"unordered\"><item><caption>o</caption>skin or eyes look yellow</item><item><caption>o</caption>pain on the right side of your stomach (abdomen)</item></list></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><list listType=\"unordered\"><item><caption>&#x2022;</caption><content styleCode=\"bold\">Psoriasis.</content> Some people using adalimumab products had new psoriasis or worsening of psoriasis they already had. Tell your healthcare provider if you develop red scaly patches or raised bumps that are filled with pus. Your healthcare provider may decide to stop your treatment with IDACIO.</item></list><paragraph><content styleCode=\"bold\">Call your healthcare provider or get medical care right away if you develop any of the above symptoms. Your treatment with IDACIO may be stopped.</content></paragraph><paragraph><content styleCode=\"bold\">The most common side effects of IDACIO include:</content></paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption>injection site reactions: redness, rash, swelling, itching, or bruising. These symptoms usually will go away within a few days. Call your healthcare provider right away if you have pain, redness or swelling around the injection site that does not go away within a few days or gets worse.</item><item><caption>&#x2022;</caption>upper respiratory infections (including sinus infections).</item><item><caption>&#x2022;</caption>headaches.</item><item><caption>&#x2022;</caption>rash.</item></list><paragraph>These are not all the possible side effects with IDACIO. Tell your healthcare provider if you have any side effect that bothers you or that does not go away. Ask your healthcare provider or pharmacist for more information. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.</paragraph></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"bold\">How should I store IDACIO? </content></paragraph><list listType=\"unordered\"><item><caption>&#x2022;</caption>Store IDACIO in the refrigerator at 36&#xBA;F to 46&#xBA;F (2&#xBA;C to 8&#xBA;C). Store IDACIO in the original carton until use to protect it from light.</item><item><caption>&#x2022;</caption><content styleCode=\"bold\">Do not freeze IDACIO</content>. Do not use IDACIO if frozen, even if it has been thawed.</item><item><caption>&#x2022;</caption>Refrigerated IDACIO may be used until the expiration date printed on the IDACIO carton. Pen or prefilled syringe. Do not use IDACIO after the expiration date.</item><item><caption>&#x2022;</caption>If needed, for example when you are traveling, you may also store IDACIO at room temperature up to 77&#xB0;F (25&#xB0;C) for up to 28 days. Store IDACIO in the original carton until use, to protect it from light.</item><item><caption>&#x2022;</caption>Throw away IDACIO if it has been kept at room temperature and not been used within 28 days.</item><item><caption>&#x2022;</caption>Record the date you first remove IDACIO from the refrigerator in the spaces provided on the carton.</item><item><caption>&#x2022;</caption>Do not store IDACIO in extreme heat or cold.</item><item><caption>&#x2022;</caption>Do not use a Pen or prefilled syringe if the liquid is cloudy, discolored, or has flakes or particles in it.</item><item><caption>&#x2022;</caption>Do not drop or crush IDACIO. The prefilled syringe is glass.</item></list><paragraph><content styleCode=\"bold\">Keep IDACIO, injection supplies, and all other medicines out of the reach of children. </content></paragraph></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"bold\">General information about the safe and effective use of IDACIO.</content></paragraph><paragraph>Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use IDACIO for a condition for which it was not prescribed. Do not give IDACIO to other people, even if they have the same condition. It may harm them. This Medication Guide summarizes the most important information about IDACIO. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about IDACIO that is written for health professionals.</paragraph></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">What are the ingredients in IDACIO? </content></paragraph><paragraph><content styleCode=\"bold\">Active ingredient: </content>adalimumab-aacf</paragraph><paragraph>IDACIO 40 mg/0.8 mL Pen, IDACIO 40 mg/0.8 mL prefilled syringe and IDACIO 40 mg/0.8 mL institutional use vial kit.</paragraph><paragraph><content styleCode=\"bold\">Inactive ingredients: </content>glacial acetic acid, trehalose, polysorbate 80, sodium chloride and Water for Injection. Sodium hydroxide is added as necessary to adjust pH.</paragraph><paragraph><content styleCode=\"bold\"> Manufactured by: </content>Fresenius Kabi USA, LLC, Lake Zurich, IL 60047, U.S.A.</paragraph><paragraph>For more product information go to www.IDACIO.com You can enroll in a patient support program by calling 1-833-522-4227 or visiting the patient support program website: https://kabicare.us/.</paragraph><paragraph>U.S. License number 2146</paragraph></td></tr></tbody></table>"],"mechanism_of_action":["12.1 Mechanism of Action Adalimumab products bind specifically to TNF-alpha and block its interaction with the p55 and p75 cell surface TNF receptors. Adalimumab products also lyse surface TNF expressing cells in vitro in the presence of complement. Adalimumab products do not bind or inactivate lymphotoxin (TNF-beta). TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Elevated concentrations of TNF are found in the synovial fluid of patients with RA, JIA, PsA, and AS and play an important role in both the pathologic inflammation and the joint destruction that are hallmarks of these diseases. Increased concentrations of TNF are also found in psoriasis plaques. In Ps, treatment with IDACIO may reduce the epidermal thickness and infiltration of inflammatory cells. The relationship between these pharmacodynamic activities and the mechanism(s) by which adalimumab products exert their clinical effects is unknown. Adalimumab products also modulate biological responses that are induced or regulated by TNF, including changes in the concentrations of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-1, and ICAM-1 with an IC 50 of 1-2 X 10 -10 M)."],"recent_major_changes":["Indications and Usage, Hidradenitis Suppurativa ( 1.8 ) 10/2023 Indications and Usage, Uveitis ( 1.9 ) 10/2023 Dosage and Administration, Juvenile Idiopathic Arthritis ( 2.2 ) 1/2024 Dosage and Administration, Crohn’s Disease ( 2.3 ) 1/2024 Dosage and Administration, Plaque Psoriasis or Adult Uveitis ( 2.5 ) 10/2023 Dosage and Administration, Hidradenitis Suppurativa ( 2.6 ) 10/2023 Dosage and Administration, General Considerations For Administration ( 2.8 ) 1/2024 Warnings and Precautions, Malignancies ( 5.2 ) 10/2023 Warnings and Precautions, Neurological Reactions ( 5.5 ) 10/2023"],"clinical_pharmacology":["12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Adalimumab products bind specifically to TNF-alpha and block its interaction with the p55 and p75 cell surface TNF receptors. Adalimumab products also lyse surface TNF expressing cells in vitro in the presence of complement. Adalimumab products do not bind or inactivate lymphotoxin (TNF-beta). TNF is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Elevated concentrations of TNF are found in the synovial fluid of patients with RA, JIA, PsA, and AS and play an important role in both the pathologic inflammation and the joint destruction that are hallmarks of these diseases. Increased concentrations of TNF are also found in psoriasis plaques. In Ps, treatment with IDACIO may reduce the epidermal thickness and infiltration of inflammatory cells. The relationship between these pharmacodynamic activities and the mechanism(s) by which adalimumab products exert their clinical effects is unknown. Adalimumab products also modulate biological responses that are induced or regulated by TNF, including changes in the concentrations of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-1, and ICAM-1 with an IC 50 of 1-2 X 10 -10 M). 12.2 Pharmacodynamics After treatment with adalimumab, a decrease in concentrations of acute phase reactants of inflammation (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) and serum cytokines (IL-6) was observed compared to baseline in patients with rheumatoid arthritis. A decrease in CRP concentrations was also observed in patients with Crohn’s disease, ulcerative colitis and hidradenitis suppurativa. Serum concentrations of matrix metalloproteinases (MMP-1 and MMP-3) that produce tissue remodeling responsible for cartilage destruction were also decreased after adalimumab administration. 12.3 Pharmacokinetics The pharmacokinetics of adalimumab were linear over the dose range of 0.5 to 10 mg/kg following administration of a single intravenous dose (adalimumab products are not approved for intravenous use). Following 20, 40, and 80 mg every other week and every week subcutaneous administration, adalimumab mean serum trough concentrations at steady state increased approximately proportionally with dose in RA patients. The mean terminal half-life was approximately 2 weeks, ranging from 10 to 20 days across studies. Healthy subjects and patients with RA displayed similar adalimumab pharmacokinetics. Adalimumab exposure in patients treated with 80 mg every other week is estimated to be comparable with that in patients treated with 40 mg every week. Absorption The average absolute bioavailability of adalimumab following a single 40 mg subcutaneous dose was 64%. The mean time to reach the maximum concentration was 5.5 days (131 ± 56 hours) and the maximum serum concentration was 4.7 ± 1.6 mcg/mL in healthy subjects following a single 40 mg subcutaneous administration of adalimumab. Distribution The distribution volume (V ss ) ranged from 4.7 to 6.0 L following intravenous administration of doses ranging from 0.25 to 10 mg/kg in RA patients. Elimination The single dose pharmacokinetics of adalimumab in RA patients were determined in several studies with intravenous doses ranging from 0.25 to 10 mg/kg. The systemic clearance of adalimumab is approximately 12 mL/hr. In long-term studies with dosing more than two years, there was no evidence of changes in clearance over time in RA patients. Patient Population Rheumatoid Arthritis and Ankylosing Spondylitis: In patients receiving 40 mg adalimumab every other week, adalimumab mean steady-state trough concentrations were approximately 5 mcg/mL and 8 to 9 mcg/mL, without and with MTX concomitant treatment, respectively. Adalimumab concentrations in the synovial fluid from five rheumatoid arthritis patients ranged from 31 to 96% of those in serum. The pharmacokinetics of adalimumab in patients with AS were similar to those in patients with RA. Psoriatic Arthritis : In patients receiving 40 mg every other week, adalimumab mean steady-state trough concentrations were 6 to 10 mcg/mL and 8.5 to 12 mcg/mL, without and with MTX concomitant treatment, respectively. Plaque Psoriasis : Adalimumab mean steady-state trough concentration was approximately 5 to 6 mcg/mL during adalimumab 40 mg every other week treatment. Adult Uveitis : Adalimumab mean steady concentration was approximately 8 to 10 mcg/mL during adalimumab 40 mg every other week treatment. Adult Hidradenitis Suppurativa : Adalimumab trough concentrations were approximately 7 to 8 mcg/mL at Week 2 and Week 4, respectively, after receiving 160 mg on Week 0 followed by 80 mg on Week 2. Mean steady-state trough concentrations at Week 12 through Week 36 were approximately 7 to 11 mcg/mL during adalimumab 40 mg every week treatment. Adult Crohn’s Disease: Adalimumab mean trough concentrations were approximately 12 mcg/mL at Week 2 and Week 4 after receiving 160 mg on Week 0 followed by 80 mg on Week 2. Mean steady-state trough concentrations were 7 mcg/mL at Week 24 and Week 56 during adalimumab 40 mg every other week treatment. Adult Ulcerative Colitis : Adalimumab mean trough concentrations were approximately 12 mcg/mL at Week 2 and Week 4 after receiving 160 mg on Week 0 followed by 80 mg on Week 2. Mean steady-state trough concentrations were approximately 8 mcg/mL and 15 mcg/mL at Week 52 after receiving a dose of adalimumab 40 mg every other week and 40 mg every week, respectively. Anti-Drug Antibody Effects on Pharmacokinetics Rheumatoid Arthritis: A trend toward higher apparent clearance of adalimumab in the presence of anti-adalimumab antibodies was identified. Hidradenitis Suppurativa: In subjects with moderate to severe HS, antibodies to adalimumab were associated with reduced serum adalimumab concentrations. In general, the extent of reduction in serum adalimumab concentrations is greater with increasing titers of antibodies to adalimumab. Specific Populations Geriatric Patients : A lower clearance with increasing age was observed in patients with RA aged 40 to >75 years. Pediatric Patients: Juvenile Idiopathic Arthritis : • 4 years to 17 years of age: The adalimumab mean steady-state trough concentrations were 6.8 mcg/mL and 10.9 mcg/mL in patients weighing <30 kg receiving 20 mg adalimumab subcutaneously every other week as monotherapy or with concomitant MTX, respectively. The adalimumab mean steady-state trough concentrations were 6.6 mcg/mL and 8.1 mcg/mL in patients weighing ≥30 kg receiving 40 mg adalimumab subcutaneously every other week as monotherapy or with MTX concomitant treatment, respectively. • 2 years to <4 years of age or 4 years of age and older weighing <15 kg: The adalimumab mean steady-state trough adalimumab concentrations were 6.0 mcg/mL and 7.9 mcg/mL in patients receiving adalimumab subcutaneously every other week as monotherapy or with MTX concomitant treatment, respectively. Pediatric Crohn's Disease : Adalimumab mean ± SD concentrations were 15.7±6.5 mcg/mL at Week 4 following 160 mg at Week 0 and 80 mg at Week 2, and 10.5±6.0 mcg/mL at Week 52 following 40 mg every other week dosing in patients weighing ≥ 40 kg. Adalimumab mean ± SD concentrations were 10.6±6.1 mcg/mL at Week 4 following dosing 80 mg at Week 0 and 40 mg at Week 2, and 6.9±3.6 mcg/mL at Week 52 following 20 mg every other week dosing in patients weighing < 40 kg. Male and Female Patients : No gender-related pharmacokinetic differences were observed after correction for a patient’s body weight. Healthy subjects and patients with rheumatoid arthritis displayed similar adalimumab pharmacokinetics. Patients with Renal or Hepatic Impairment: No pharmacokinetic data are available in patients with hepatic or renal impairment. Rheumatoid factor or CRP concentrations: Minor increases in apparent clearance were predicted in RA patients receiving doses lower than the recommended dose and in RA patients with high rheumatoid factor or CRP concentrations. These increases are not likely to be clinically important. Drug Interaction Studies: Methotrexate : MTX reduced adalimumab apparent clearance after single and multiple dosing by 29% and 44% respectively, in patients with RA [see Drug Interactions ( 7.1 )] ."],"indications_and_usage":["1 INDICATIONS AND USAGE IDACIO is a tumor necrosis factor (TNF) blocker indicated for: • Rheumatoid Arthritis (RA) ( 1.1 ): reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active RA . • Juvenile Idiopathic Arthritis (JIA) ( 1.2 ): reducing signs and symptoms of moderately to severely active polyarticular JIA in patients 2 years of age and older. • Psoriatic Arthritis (PsA) ( 1.3 ): reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active PsA. • Ankylosing Spondylitis (AS) ( 1.4 ): reducing signs and symptoms in adult patients with active AS. • Crohn’s Disease (CD) ( 1.5 ): treatment of moderately to severely active Crohn’s disease in adults and pediatric patients 6 years of age and older. • Ulcerative Colitis (UC) ( 1.6 ): treatment of moderately to severely active ulcerative colitis in adult patients. Limitations of Use: Effectiveness has not been established in patients who have lost response to or were intolerant to TNF blockers. • Plaque Psoriasis (Ps) ( 1.7 ): treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. • Hidradenitis Suppurativa (HS) ( 1.8 ): treatment of moderate to severe hidradenitis suppurativa in adult patients. • Uveitis (UV) ( 1.9 ): treatment of non-infectious intermediate, posterior, and panuveitis in adult patients. 1.1 Rheumatoid Arthritis IDACIO is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis. IDACIO can be used alone or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs). 1.2 Juvenile Idiopathic Arthritis IDACIO is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older. IDACIO can be used alone or in combination with methotrexate. 1.3 Psoriatic Arthritis IDACIO is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis. IDACIO can be used alone or in combination with non-biologic DMARDs. 1.4 Ankylosing Spondylitis IDACIO is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis. 1.5 Crohn’s Disease IDACIO is indicated for the treatment of moderately to severely active Crohn’s disease in adults and pediatric patients 6 years of age and older. 1.6 Ulcerative Colitis IDACIO is indicated for the treatment of moderately to severely active ulcerative colitis in adult patients. Limitations of Use The effectiveness of adalimumab products has not been established in patients who have lost response to or were intolerant to TNF blockers [see Clinical Studies ( 14.7 )] . 1.7 Plaque Psoriasis IDACIO is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. IDACIO should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician [see Warnings and Precautions ( 5 )] . 1.8 Hidradenitis Suppurativa IDACIO is indicated for the treatment of moderate to severe hidradenitis suppurativa in adult patients. 1.9 Uveitis IDACIO is indicated for the treatment of non-infectious intermediate, posterior, and panuveitis in adult patients."],"warnings_and_cautions":["5 WARNINGS AND PRECAUTIONS • Serious infections: Do not start IDACIO during an active infection. If an infection develops, monitor carefully, and stop IDACIO if infection becomes serious. ( 5.1 ) • Invasive fungal infections: For patients who develop a systemic illness on IDACIO, consider empiric antifungal therapy for those who reside or travel to regions where mycoses are endemic. ( 5.1 ) • Malignancies: Incidence of malignancies was greater in adalimumab-treated patients than in controls ( 5.2 ) • Anaphylaxis or serious hypersensitivity reactions may occur ( 5.3 ) • Hepatitis B virus reactivation: Monitor HBV carriers during and several months after therapy. If reactivation occurs, stop IDACIO and begin anti‑ viral therapy. ( 5.4 ) • Demyelinating disease: Exacerbation or new onset, may occur. ( 5.5 ) • Cytopenias, pancytopenia: Advise patients to seek immediate medical attention if symptoms develop and consider stopping IDACIO. ( 5.6 ) • Heart failure: Worsening or new onset, may occur. ( 5.8 ) • Lupus-like syndrome: Stop IDACIO if syndrome develops. ( 5.9 ) 5.1 Serious Infections Patients treated with adalimumab products including IDACIO are at increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death. Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic pathogens including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis and tuberculosis have been reported with TNF blockers. Patients have frequently presented with disseminated rather than localized disease. The concomitant use of a TNF blocker and abatacept or anakinra was associated with a higher risk of serious infections in patients with rheumatoid arthritis (RA); therefore, the concomitant use of IDACIO and these biologic products is not recommended in the treatment of patients with RA [see Warnings and Precautions ( 5.7 , 5.11 ) and Drug Interactions ( 7.2 )] . Treatment with IDACIO should not be initiated in patients with an active infection, including localized infections. Patients 65 years of age and older, patients with co-morbid conditions and/or patients taking concomitant immunosuppressants (such as corticosteroids or methotrexate), may be at greater risk of infection. Consider the risks and benefits of treatment prior to initiating therapy in patients: • with chronic or recurrent infection; • who have been exposed to tuberculosis; • with a history of an opportunistic infection; • who have resided or traveled in areas of endemic tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis; or • with underlying conditions that may predispose them to infection. Tuberculosis Cases of reactivation of tuberculosis and new onset tuberculosis infections have been reported in patients receiving adalimumab products, including patients who have previously received treatment for latent or active tuberculosis. Reports included cases of pulmonary and extrapulmonary (i.e., disseminated) tuberculosis. Evaluate patients for tuberculosis risk factors and test for latent infection prior to initiating IDACIO and periodically during therapy. Treatment of latent tuberculosis infection prior to therapy with TNF blocking agents has been shown to reduce the risk of tuberculosis reactivation during therapy. Prior to initiating IDACIO, assess if treatment for latent tuberculosis is needed; and consider an induration of ≥ 5 mm a positive tuberculin skin test result, even for patients previously vaccinated with Bacille Calmette-Guerin (BCG). Consider anti-tuberculosis therapy prior to initiation of IDACIO in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed, and for patients with a negative test for latent tuberculosis but having risk factors for tuberculosis infection. Despite prophylactic treatment for tuberculosis, cases of reactivated tuberculosis have occurred in patients treated with adalimumab products. Consultation with a physician with expertise in the treatment of tuberculosis is recommended to aid in the decision whether initiating anti- tuberculosis therapy is appropriate for an individual patient. Strongly consider tuberculosis in the differential diagnosis in patients who develop a new infection during IDACIO treatment, especially in patients who have previously or recently traveled to countries with a high prevalence of tuberculosis, or who have had close contact with a person with active tuberculosis. Monitoring Closely monitor patients for the development of signs and symptoms of infection during and after treatment with IDACIO, including the development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. Tests for latent tuberculosis infection may also be falsely negative while on therapy with IDACIO. Discontinue IDACIO if a patient develops a serious infection or sepsis. For a patient who develops a new infection during treatment with IDACIO, closely monitor them, perform a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and initiate appropriate antimicrobial therapy. Invasive Fungal Infections If patients develop a serious systemic illness and they reside or travel in regions where mycoses are endemic, consider invasive fungal infection in the differential diagnosis. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider appropriate empiric antifungal therapy, taking into account both the risk for severe fungal infection and the risks of antifungal therapy, while a diagnostic workup is being performed. To aid in the management of such patients, consider consultation with a physician with expertise in the diagnosis and treatment of invasive fungal infections. 5.2 Malignancies Consider the risks and benefits of TNF-blocker treatment including IDACIO prior to initiating therapy in patients with a known malignancy other than a successfully treated non-melanoma skin cancer (NMSC) or when considering continuing a TNF blocker in patients who develop a malignancy. Malignancies in Adults In the controlled portions of clinical trials of some TNF-blockers, including adalimumab products, more cases of malignancies have been observed among TNF-blocker-treated adult patients compared to control-treated adult patients. During the controlled portions of 39 global adalimumab clinical trials in adult patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn’s disease (CD), ulcerative colitis (UC), plaque psoriasis (Ps), hidradenitis suppurativa (HS) and uveitis (UV), malignancies, other than non-melanoma (basal cell and squamous cell) skin cancer, were observed at a rate (95% confidence interval) of 0.7 (0.48, 1.03) per 100 patient-years among 7973 adalimumab-treated patients versus a rate of 0.7 (0.41, 1.17) per 100 patient-years among 4848 control-treated patients (median duration of treatment of 4 months for adalimumab-treated patients and 4 months for control-treated patients). In 52 global controlled and uncontrolled clinical trials of adalimumab in adult patients with RA, PsA, AS, CD, UC, Ps, HS, and UV, the most frequently observed malignancies, other than lymphoma and NMSC, were breast, colon, prostate, lung, and melanoma. The malignancies in adalimumab-treated patients in the controlled and uncontrolled portions of the studies were similar in type and number to what would be expected in the general U.S. population according to the SEER database (adjusted for age, gender, and race). 1 In controlled trials of other TNF blockers in adult patients at higher risk for malignancies (i.e., patients with COPD with a significant smoking history and cyclophosphamide-treated patients with Wegener’s granulomatosis), a greater portion of malignancies occurred in the TNF blocker group compared to the control group. Non-Melanoma Skin Cancer During the controlled portions of 39 global adalimumab clinical trials in adult patients with RA, PsA, AS, CD, UC, Ps, HS, and UV, the rate (95% confidence interval) of NMSC was 0.8 (0.52, 1.09) per 100 patient-years among adalimumab-treated patients and 0.2 (0.10, 0.59) per 100 patient-years among control-treated patients. Examine all patients, and in particular patients with a medical history of prior prolonged immunosuppressant therapy or psoriasis patients with a history of PUVA treatment for the presence of NMSC prior to and during treatment with IDACIO. Lymphoma and Leukemia In the controlled portions of clinical trials of all the TNF-blockers in adults, more cases of lymphoma have been observed among TNF-blocker-treated patients compared to control-treated patients. In the controlled portions of 39 global adalimumab clinical trials in adult patients with RA, PsA, AS, CD, UC, Ps, HS, and UV, 2 lymphomas occurred among 7973 adalimumab-treated patients versus 1 among 4848 control-treated patients. In 52 global controlled and uncontrolled clinical trials of adalimumab in adult patients with RA, PsA, AS, CD, UC, Ps, HS, and UV with a median duration of approximately 0.7 years, including 24,605 patients and over 40,215 patient- years of adalimumab, the observed rate of lymphomas was approximately 0.11 per 100 patient- years. This is approximately 3-fold higher than expected in the general U.S. population according to the SEER database (adjusted for age, gender, and race). 1 Rates of lymphoma in clinical trials of adalimumab cannot be compared to rates of lymphoma in clinical trials of other TNF blockers and may not predict the rates observed in a broader patient population. Patients with RA and other chronic inflammatory diseases, particularly those with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at a higher risk (up to several fold) than the general population for the development of lymphoma, even in the absence of TNF blockers. Post-marketing cases of acute and chronic leukemia have been reported in association with TNF-blocker use in RA and other indications. Even in the absence of TNF-blocker therapy, patients with RA may be at a higher risk (approximately 2-fold) than the general population for the development of leukemia. Malignancies in Pediatric Patients and Young Adults Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blockers (initiation of therapy ≤ 18 years of age), of which IDACIO is a member. Approximately half the cases were lymphomas, including Hodgkin's and non-Hodgkin's lymphoma. The other cases represented a variety of different malignancies and included rare malignancies usually associated with immunosuppression and malignancies that are not usually observed in children and adolescents. The malignancies occurred after a median of 30 months of therapy (range 1 to 84 months). Most of the patients were receiving concomitant immunosuppressants. These cases were reported post-marketing and are derived from a variety of sources including registries and spontaneous postmarketing reports. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including adalimumab products. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn's disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with the immunosuppressants azathioprine or 6-mercaptopurine (6–MP) concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants. The potential risk with the combination of azathioprine or 6‑mercaptopurine and IDACIO should be carefully considered. 5.3 Hypersensitivity Reactions Anaphylaxis and angioneurotic edema have been reported following administration of adalimumab products. If an anaphylactic or other serious allergic reaction occurs, immediately discontinue administration of IDACIO and institute appropriate therapy. In clinical trials of adalimumab, hypersensitivity reactions (e.g., rash, anaphylactoid reaction, fixed drug reaction, non-specified drug reaction, urticaria) have been observed. 5.4 Hepatitis B Virus Reactivation Use of TNF blockers, including IDACIO, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of this virus. In some instances, HBV reactivation occurring in conjunction with TNF blocker therapy has been fatal. The majority of these reports have occurred in patients concomitantly receiving other medications that suppress the immune system, which may also contribute to HBV reactivation. Evaluate patients at risk for HBV infection for prior evidence of HBV infection before initiating TNF blocker therapy. Exercise caution in prescribing TNF blockers for patients identified as carriers of HBV. Adequate data are not available on the safety or efficacy of treating patients who are carriers of HBV with anti-viral therapy in conjunction with TNF blocker therapy to prevent HBV reactivation. For patients who are carriers of HBV and require treatment with TNF blockers, closely monitor such patients for clinical and laboratory signs of active HBV infection throughout therapy and for several months following termination of therapy. In patients who develop HBV reactivation, stop IDACIO and initiate effective anti-viral therapy with appropriate supportive treatment. The safety of resuming TNF blocker therapy after HBV reactivation is controlled is not known. Therefore, exercise caution when considering resumption of IDACIO therapy in this situation and monitor patients closely. 5.5 Neurologic Reactions Use of TNF blocking agents, including adalimumab products, has been associated with rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease, including multiple sclerosis (MS) and optic neuritis, and peripheral demyelinating disease, including Guillain-Barré syndrome. Exercise caution in considering the use of IDACIO in patients with preexisting or recent-onset central or peripheral nervous system demyelinating disorders; discontinuation of IDACIO should be considered if any of these disorders develop. There is a known association between intermediate uveitis and central demyelinating disorders. 5.6 Hematological Reactions Rare reports of pancytopenia including aplastic anemia have been reported with TNF blocking agents. Adverse reactions of the hematologic system, including medically significant cytopenia (e.g., thrombocytopenia, leukopenia) have been infrequently reported with adalimumab products. The causal relationship of these reports to adalimumab products remains unclear. Advise all patients to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever, bruising, bleeding, pallor) while on IDACIO. Consider discontinuation of IDACIO therapy in patients with confirmed significant hematologic abnormalities. 5.7 Increased Risk of Infection when Used with Anakinra Concurrent use of anakinra (an interleukin-1 antagonist) and another TNF-blocker, was associated with a greater proportion of serious infections and neutropenia and no added benefit compared with the TNF-blocker alone in patients with RA. Therefore, the combination of IDACIO and anakinra is not recommended [see Drug Interactions ( 7.2 )]. 5.8 Heart Failure Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers. Cases of worsening CHF have also been observed with adalimumab products. Adalimumab products have not been formally studied in patients with CHF; however, in clinical trials of another TNF blocker, a higher rate of serious CHF-related adverse reactions was observed. Exercise caution when using IDACIO in patients who have heart failure and monitor them carefully. 5.9 Autoimmunity Treatment with adalimumab products may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome. If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with IDACIO, discontinue treatment [see Adverse Reactions ( 6.1 )] . 5.10 Immunizations In a placebo-controlled clinical trial of patients with RA, no difference was detected in anti‑ pneumococcal antibody response between adalimumab and placebo treatment groups when the pneumococcal polysaccharide vaccine and influenza vaccine were administered concurrently with adalimumab. Similar proportions of patients developed protective levels of anti-influenza antibodies between adalimumab and placebo treatment groups; however, titers in aggregate to influenza antigens were moderately lower in patients receiving adalimumab. The clinical significance of this is unknown. Patients on IDACIO may receive concurrent vaccinations, except for live vaccines. No data are available on the secondary transmission of infection by live vaccines in patients receiving adalimumab products. It is recommended that pediatric patients, if possible, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating IDACIO therapy. Patients on IDACIO may receive concurrent vaccinations, except for live vaccines. The safety of administering live or live-attenuated vaccines in infants exposed to adalimumab products in utero is unknown. Risks and benefits should be considered prior to vaccinating (live or live- attenuated) exposed infants [see Use in Specific Populations ( 8.1 , 8.4 )] . 5.11 Increased Risk of Infection When Used with Abatacept In controlled trials, the concurrent administration of TNF-blockers and abatacept was associated with a greater proportion of serious infections than the use of a TNF-blocker alone; the combination therapy, compared to the use of a TNF-blocker alone, has not demonstrated improved clinical benefit in the treatment of RA. Therefore, the combination of abatacept with TNF-blockers including IDACIO is not recommended [see Drug Interactions ( 7.2 )] ."],"clinical_studies_table":["<table ID=\"_Ref180065042\" width=\"100%\"><caption>Table 3: ACR Responses in Studies RA-II and RA-III (Percent of Patients)</caption><col width=\"16%\"/><col width=\"16%\"/><col width=\"16%\"/><col width=\"16%\"/><col width=\"16%\"/><col width=\"19%\"/><tbody><tr><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"/><td colspan=\"3\" align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Study RA-II Monotherapy (26 weeks)</content></paragraph></td><td colspan=\"2\" align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Study RA-III Methotrexate Combination (24 and 52 weeks)</content></paragraph></td></tr><tr><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Response</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Placebo</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Adalimumab</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Adalimumab</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Placebo/MTX</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Adalimumab/MTX</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>40 mg every</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>40 mg weekly</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>40 mg every</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>other week</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>other week</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>N=110</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>N=113</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>N=103</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>N=200</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>N=207</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">ACR20</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Month 6</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>19%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>46%<sup>*</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>53%<sup>*</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>30%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>63%<sup>*</sup></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Month 12</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NA</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NA</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NA</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>24%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>59%<sup>*</sup></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">ACR50</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Month 6</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>8%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>22%<sup>*</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>35%<sup>*</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>10%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>39%<sup>*</sup></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Month 12</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NA</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NA</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NA</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>10%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>42%<sup>*</sup></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">ACR70</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Month 6</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>2%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>12%<sup>*</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>18%<sup>*</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>3%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>21%<sup>*</sup></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Month 12</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NA</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NA</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NA</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>5%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>23%<sup>*</sup></paragraph></td></tr><tr><td colspan=\"6\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>* p&lt;0.01, adalimumab <content styleCode=\"italics\">vs.</content>placebo</paragraph></td></tr></tbody></table>","<table ID=\"_Ref180065104\" width=\"100%\" cellpadding=\"0pt\"><caption>Table 4: Components of ACR Response in Studies RA-II and RA-III</caption><col width=\"27%\"/><col width=\"11%\"/><col width=\"7%\"/><col width=\"9%\"/><col width=\"6%\"/><col width=\"11%\"/><col width=\"7%\"/><col width=\"13%\"/><col width=\"9%\"/><tbody><tr><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"/><td colspan=\"4\" align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Study RA-II</content></paragraph></td><td colspan=\"4\" align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Study RA-III</content></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Parameter (median)</content></paragraph></td><td colspan=\"2\" align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Placebo N=110</content></paragraph></td><td colspan=\"2\" align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Adalimumab<sup>a</sup> N=113</content></paragraph></td><td colspan=\"2\" align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Placebo/MTX N=200</content></paragraph></td><td colspan=\"2\" align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Adalimumab<sup>a</sup>/MTX N=207</content></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Baseline</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Wk 26</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Baseline</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Wk 26</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Baseline</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Wk 24</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Baseline</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Wk 24</content></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Number of tender joints (0-68)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>35</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>26</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>31</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>16<sup>*</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>26</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>15</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>24</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>8<sup>*</sup></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Number of swollen joints (0-66)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>19</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>16</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>18</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>10<sup>*</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>17</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>11</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>18</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>5<sup>*</sup></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Physician global assessment<sup>b</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>7.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>6.1</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>6.6</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>3.7<sup>*</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>6.3</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>3.5</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>6.5</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>2.0<sup>*</sup></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Patient global assessment<sup>b</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>7.5</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>6.3</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>7.5</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>4.5<sup>*</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>5.4</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>3.9</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>5.2</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>2.0<sup>*</sup></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Pain<sup>b</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>7.3</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>6.1</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>7.3</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>4.1<sup>*</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>6.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>3.8</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>5.8</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>2.1<sup>*</sup></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Disability index (HAQ)<sup>c</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>2.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1.9</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1.9</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1.5<sup>*</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1.5</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1.3</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1.5</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.8<sup>*</sup></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>CRP (mg/dL)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>3.9</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>4.3</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>4.6</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1.8<sup>*</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.9</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.4<sup>*</sup></paragraph></td></tr><tr><td colspan=\"9\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><sup>a </sup> 40 mg adalimumab administered every other week</paragraph><paragraph><sup>b </sup> Visual analogue scale; 0 = best, 10 = worst</paragraph><paragraph><sup>c </sup>Disability Index of the Health Assessment Questionnaire; 0 = best, 3 = worst, measures the patient&#x2019;s ability to perform the following: dress/groom, arise, eat, walk, reach, grip, maintain hygiene, and maintain daily activity</paragraph><paragraph>* p&lt;0.001, adalimumab <content styleCode=\"italics\">vs. </content>placebo, based on mean change from baseline</paragraph></td></tr></tbody></table>","<table ID=\"_Ref180065413\" width=\"100.08%\"><caption>Table 5: ACR Response in Study RA-V (Percent of Patients)</caption><col width=\"25%\"/><col width=\"25%\"/><col width=\"25%\"/><col width=\"25%\"/><tbody><tr><td valign=\"middle\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Response</content></paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">MTX<sup>b</sup> N=257</content></paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Adalimumab<sup>c</sup> N=274</content></paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Adalimumab/MTX  N=268</content></paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">ACR20 </content> Week 52  Week 104</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\"> </content>63% 56%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> 54% 49%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\"> </content>73% 69%</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">ACR50 </content> Week 52  Week 104</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\"> </content>46% 43%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> 41% 37%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\"> </content>62% 59%</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">ACR70 </content> Week 52  Week 104</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\"> </content>27% 28%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> 26% 28%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\"> </content>46% 47%</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Major Clinical Response <sup>a</sup></paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>28%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>25%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>49%</paragraph></td></tr><tr><td colspan=\"4\" valign=\"middle\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><sup>a</sup> Major clinical response is defined as achieving an ACR70 response for a continuous six month period</paragraph><paragraph><sup>b</sup> p&lt;0.05, adalimumab/MTX <content styleCode=\"italics\">vs. </content>MTX for ACR 20 </paragraph><paragraph>p&lt;0.001, adalimumab/MTX <content styleCode=\"italics\">vs. </content>MTX for ACR 50 and 70, and Major Clinical Response</paragraph><paragraph><sup>c</sup> p&lt;0.001, adalimumab/MTX <content styleCode=\"italics\">vs. </content>adalimumab</paragraph></td></tr></tbody></table>","<table ID=\"_Ref180065459\" width=\"100%\"><caption>Table 6: Radiographic Mean Changes Over 12 Months in Study RA-III</caption><col width=\"15%\"/><col width=\"18%\"/><col width=\"20%\"/><col width=\"32%\"/><col width=\"15%\"/><tbody><tr><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Placebo/MTX</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Adalimumab/MTX</paragraph><paragraph>40 mg every other week</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Placebo/MTX&#x2011;Adalimumab/MTX (95% Confidence</paragraph><paragraph>Interval*)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>P-value**</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Total Sharp score</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>2.7</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.1</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>2.6 (1.4, 3.8)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>&lt;0.001</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Erosion score</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1.6</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1.6 (0.9, 2.2)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>&lt;0.001</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>JSN score</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.1</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.9 (0.3, 1.4)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.002</paragraph></td></tr><tr><td colspan=\"5\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>*95% confidence intervals for the differences in change scores between MTX and adalimumab.</paragraph><paragraph>**Based on rank analysis</paragraph></td></tr></tbody></table>","<table ID=\"_Ref180065509\" width=\"100.18%\"><caption>Table 7: Radiographic Mean Change* in Study RA-V</caption><col width=\"20%\"/><col width=\"20%\"/><col width=\"20%\"/><col width=\"20%\"/><col width=\"20%\"/><tbody><tr><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"/><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">MTX<sup>a</sup> N=257</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Adalimumab<sup>a</sup>,<sup>b</sup> N=274</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Adalimumab/MTX N=268</content></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>52 Weeks</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Total Sharp score</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>5.7 (4.2, 7.3)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>3.0 (1.7, 4.3)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1.3 (0.5, 2.1)</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Erosion score</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>3.7 (2.7, 4.8)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1.7 (1.0, 2.4)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.8 (0.4, 1.2)</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>JSN score</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>2.0 (1.2, 2.8)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1.3 (0.5, 2.1)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.5 (0.0, 1.0)</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>104 Weeks</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Total Sharp score</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>10.4 (7.7, 13.2)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>5.5 (3.6, 7.4)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1.9 (0.9, 2.9)</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Erosion score</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>6.4 (4.6, 8.2)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>3.0 (2.0, 4.0)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1.0 (0.4, 1.6)</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>JSN score</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>4.1 (2.7, 5.4)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>2.6 (1.5, 3.7)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.9 (0.3, 1.5)</paragraph></td></tr><tr><td colspan=\"5\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><sup>* </sup>mean (95% confidence interval)</paragraph><paragraph><sup>a </sup>p&lt;0.001, adalimumab /MTX <content styleCode=\"italics\">vs. </content>MTX at 52 and 104 weeks and for adalimumab /MTX <content styleCode=\"italics\">vs</content> adalimumab at 104 weeks</paragraph><paragraph><sup>b </sup>p&lt;0.01, for adalimumab /MTX <content styleCode=\"italics\">vs. </content>adalimumab at 52 weeks</paragraph></td></tr></tbody></table>","<table ID=\"Table8\" width=\"100%\"><caption>Table 8: ACR Response in Study PsA-I (Percent of Patients)</caption><col width=\"33%\"/><col width=\"33%\"/><col width=\"33%\"/><tbody><tr><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Placebo N=162</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Adalimumab* N=151</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">ACR20</content></paragraph><paragraph> Week 12</paragraph><paragraph> Week 24</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\"> </content>14% 15%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\"> </content>58% 57%</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">ACR50</content></paragraph><paragraph> Week 12</paragraph><paragraph> Week 24</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\"> </content>4% 6%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\"> </content>36% 39%</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">ACR70</content></paragraph><paragraph> Week 12</paragraph><paragraph> Week 24</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\"> </content>1% 1%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\"> </content>20% 23%</paragraph></td></tr><tr><td colspan=\"3\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>* p&lt;0.001 for all comparisons between adalimumab and placebo</paragraph></td></tr></tbody></table>","<table ID=\"Table9\" width=\"100%\" cellpadding=\"0pt\"><caption>Table 9: Components of Disease Activity in Study PsA-I</caption><col width=\"39%\"/><col width=\"16%\"/><col width=\"15%\"/><col width=\"16%\"/><col width=\"15%\"/><tbody><tr><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"/><td colspan=\"2\" align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule \"><paragraph>Placebo N=162</paragraph></td><td colspan=\"2\" align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule \"><paragraph>Adalimumab* N=151</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Parameter: median</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Baseline</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>24 weeks</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Baseline</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>24 weeks</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Number of tender joints<sup>a</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>23.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>17.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>20.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>5.0</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Number of swollen joints<sup>b</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>11.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>9.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>11.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>3.0</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Physician global assessment<sup>c</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>53.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>49.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>55.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>16.0</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Patient global assessment<sup>c</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>49.5</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>49.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>48.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>20.0</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Pain<sup>c</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>49.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>49.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>54.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>20.0</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Disability index (HAQ) <sup>d</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.9</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.4</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>CRP (mg/dL)<sup>e</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.8</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.7</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.8</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.2</paragraph></td></tr><tr><td colspan=\"5\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><sup>* </sup>p&lt;0.001 for adalimumab <content styleCode=\"italics\">vs. </content>placebo comparisons based on median changes</paragraph><paragraph><sup>a </sup>Scale 0-78</paragraph><paragraph><sup>b </sup>Scale 0-76</paragraph><paragraph><sup>c </sup>Visual analog scale; 0=best, 100=worst</paragraph><paragraph><sup>d </sup>Disability Index of the Health Assessment Questionnaire; 0=best, 3=worst; measures the patient&#x2019;s ability to perform the following: dress/groom, arise, eat, walk, reach, grip, maintain hygiene, and maintain daily activity.</paragraph><paragraph><sup>e </sup>Normal range: 0-0.287 mg/dL</paragraph></td></tr></tbody></table>","<table ID=\"_Ref180065774\" width=\"100%\"><caption>Table 10: Change in Modified Total Sharp Score in Psoriatic Arthritis</caption><col width=\"25%\"/><col width=\"25%\"/><col width=\"25%\"/><col width=\"25%\"/><tbody><tr><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Placebo N=141</content></paragraph></td><td colspan=\"2\" align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Adalimumab N=133</content></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Week 24</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Week 24</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Week 48</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Baseline mean</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>22.1</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>23.4</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>23.4</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Mean Change &#xB1; SD</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.9 &#xB1; 3.1</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>-0.1 &#xB1; 1.7</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>-0.2 &#xB1; 4.9*</paragraph></td></tr><tr><td colspan=\"4\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>* &lt;0.001 for the difference between adalimumab, Week 48 and Placebo, Week 24 (primary analysis)</paragraph></td></tr></tbody></table>","<table ID=\"_Ref180065845\" width=\"100%\"><caption>Table 11: Components of Ankylosing Spondylitis Disease Activity</caption><col width=\"20%\"/><col width=\"20%\"/><col width=\"20%\"/><col width=\"20%\"/><col width=\"20%\"/><tbody><tr><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"/><td colspan=\"2\" align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Placebo N=107</paragraph></td><td colspan=\"2\" align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Adalimumab N=208</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Baseline mean</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Week 24 mean</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Baseline mean</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Week 24 mean</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>ASAS 20 Response Criteria*</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Patient&#x2019;s Global Assessment of Disease   Activity<sup>a</sup>*</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>65</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>60</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>63</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>38</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Total back pain*</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>67</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>58</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>65</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>37</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Inflammation<sup>b</sup>*</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>6.7</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>5.6</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>6.7</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>3.6</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>BASFI<sup>c</sup>*</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>56</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>51</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>52</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>34</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>BASDAI<sup>d</sup> score*</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>6.3</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>5.5</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>6.3</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>3.7</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>BASMI<sup>e</sup> score*</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>4.2</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>4.1</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>3.8</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>3.3</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Tragus to wall (cm)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>15.9</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>15.8</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>15.8</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>15.4</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Lumbar flexion (cm)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>4.1</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>4.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>4.2</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>4.4</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Cervical rotation (degrees)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>42.2</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>42.1</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>48.4</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>51.6</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Lumbar side flexion (cm)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>8.9</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>9.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>9.7</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>11.7</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Intermalleolar distance (cm)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>92.9</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>94.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>93.5</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>100.8</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>CRP<sup>f</sup>*</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>2.2</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>2.0</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1.8</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.6</paragraph></td></tr><tr><td colspan=\"5\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><sup>a </sup>Percent of subjects with at least a 20% and 10-unit improvement measured on a Visual Analog Scale (VAS) with 0 = &#x201C;none&#x201D; and 100 = &#x201C;severe&#x201D;</paragraph><paragraph><sup>b </sup>mean of questions 5 and 6 of BASDAI (defined in &#x2018;d&#x2019;)</paragraph><paragraph><sup>c </sup>Bath Ankylosing Spondylitis Functional Index</paragraph><paragraph><sup>d </sup>Bath Ankylosing Spondylitis Disease Activity Index</paragraph><paragraph><sup>e </sup>Bath Ankylosing Spondylitis Metrology Index</paragraph><paragraph><sup>f </sup>C-Reactive Protein (mg/dL)</paragraph><paragraph><sup>* </sup>statistically significant for comparisons between adalimumab and placebo at Week 24</paragraph></td></tr></tbody></table>","<table ID=\"_Ref180065974\" width=\"100%\"><caption>Table 12: Induction of Clinical Remission in Studies CD-I and CD-II (Percent of Patients)</caption><col width=\"20%\"/><col width=\"20%\"/><col width=\"20%\"/><col width=\"20%\"/><col width=\"20%\"/><tbody><tr><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"/><td colspan=\"2\" align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">CD-I</content></paragraph></td><td colspan=\"2\" align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">CD-II</content></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Placebo N=74</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Adalimumab 160/80 mg N=76</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Placebo N=166</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Adalimumab 160/80 mg N=159</content></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Week 4</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Clinical remission</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>12%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>36%*</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>7%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>21%*</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Clinical response</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>34%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>58%**</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>34%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>52%**</paragraph></td></tr><tr><td colspan=\"5\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Clinical remission is CDAI score &lt; 150; clinical response is decrease in CDAI of at least 70 points.</paragraph><paragraph>* p&lt;0.001 for adalimumab <content styleCode=\"italics\">vs. </content>placebo pairwise comparison of proportions</paragraph><paragraph>** p&lt;0.01 for adalimumab <content styleCode=\"italics\">vs. </content>placebo pairwise comparison of proportions</paragraph></td></tr></tbody></table>","<table ID=\"_Ref180066011\" width=\"100%\"><caption>Table 13: Maintenance of Clinical Remission in CD-III (Percent of Patients)</caption><col width=\"33%\"/><col width=\"33%\"/><col width=\"33%\"/><tbody><tr><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Placebo</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">40 mg Adalimumab</content></paragraph><paragraph><content styleCode=\"bold\">every other week</content></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">N=170</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">N=172</content></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Week 26</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Clinical remission</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>17%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>40%*</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Clinical response</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>28%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>54%*</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Week 56</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Clinical remission</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>12%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>36%*</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Clinical response</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>18%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>43%*</paragraph></td></tr><tr><td colspan=\"3\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Clinical remission is CDAI score &lt; 150; clinical response is decrease in CDAI of at least 70 points.</paragraph><paragraph>*p&lt;0.001 for adalimumab vs. placebo pairwise comparisons of proportions</paragraph></td></tr></tbody></table>","<table ID=\"_Ref180066070\" width=\"100%\"><caption>Table 14: Clinical Remission and Clinical Response in Study PCD-I</caption><col width=\"33%\"/><col width=\"33%\"/><col width=\"33%\"/><tbody><tr><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Low Maintenance Dose<sup>&#x2020;</sup> (20 or 10 mg every other week) N = 95</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">High Maintenance Dose<sup>#</sup> (40 or 20 mg every other week) N = 93</content></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Week 26</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Clinical Remission<sup>&#x2021;</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>28%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>39%</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Clinical Response<sup>&#xA7;</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>48%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>59%</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Week 52</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Clinical Remission<sup>&#x2021;</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>23%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>33%</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Clinical Response<sup>&#xA7;</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>28%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>42%</paragraph></td></tr><tr><td colspan=\"3\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><sup>&#x2020; </sup>The low maintenance dose was 20 mg every other week for patients weighing &#x2265; 40 kg and 10 mg every other week for patients weighing &lt; 40 kg.</paragraph><paragraph><sup># </sup>The high maintenance dose was 40 mg every other week for patients weighing &#x2265; 40 kg and 20 mg every other week for patients weighing &lt; 40 kg.</paragraph><paragraph><sup>&#x2021; </sup>Clinical remission defined as PCDAI &#x2264; 10.</paragraph><paragraph><sup>&#xA7; </sup>Clinical response defined as reduction in PCDAI of at least 15 points from baseline.</paragraph></td></tr></tbody></table>","<table ID=\"_Ref180066108\" width=\"100%\"><caption>Table 15: Induction of Clinical Remission in Studies UC-I and UC-II and Sustained Clinical Remission in Study UC-II (Percent of Patients)</caption><col width=\"14%\"/><col width=\"14%\"/><col width=\"14%\"/><col width=\"14%\"/><col width=\"14%\"/><col width=\"16%\"/><col width=\"14%\"/><tbody><tr><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"/><td colspan=\"3\" align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Study UC-I</content></paragraph></td><td colspan=\"3\" align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Study UC-II</content></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Placebo N=130</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Adalimumab 160/80</content></paragraph><paragraph><content styleCode=\"bold\">mg N=130</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Treatment Difference (95% CI)</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Placebo N=246</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Adalimumab 160/80</content></paragraph><paragraph><content styleCode=\"bold\">mg N=248</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Treatment Difference (95% CI)</content></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule \"><paragraph>Induction of Clinical</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>9.2%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>18.5%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule \"><paragraph>9.3%*</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>9.3%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>16.5%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule \"><paragraph>7.2%*</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule \"><paragraph>Remission (Clinical</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule \"><paragraph>(0.9%,</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule \"><paragraph>(1.2%,</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph>Remission at Week 8)</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph>17.6%)</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph>12.9%)</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Sustained Clinical Remission (Clinical Remission at both Weeks 8 and 52)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>N/A</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>N/A</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>N/A</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>4.1%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>8.5%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>4.4%* (0.1%, 8.6%)</paragraph></td></tr><tr><td colspan=\"7\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Clinical remission is defined as Mayo score &#x2264; 2 with no individual subscores &gt; 1.</paragraph><paragraph>CI=Confidence interval</paragraph><paragraph><content styleCode=\"bold\">* </content>p&lt;0.05 for adalimumab <content styleCode=\"italics\">vs. </content>placebo pairwise comparison of proportions</paragraph></td></tr></tbody></table>","<table ID=\"_Ref180066261\" width=\"100%\"><caption>Table 16: Efficacy Results at 16 Weeks in Study Ps-I Number of Subjects (%)</caption><col width=\"33%\"/><col width=\"33%\"/><col width=\"33%\"/><tbody><tr><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Adalimumab 40 mg every other week</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Placebo</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>N = 814</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>N = 398</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>PGA: <content styleCode=\"italics\">Clear </content>or <content styleCode=\"italics\">minimal</content>*</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>506 (62%)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>17 (4%)</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>PASI 75</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>578 (71%)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>26 (7%)</paragraph></td></tr><tr><td colspan=\"3\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>* Clear = no plaque elevation, no scale, plus or minus hyperpigmentation or diffuse pink or red coloration</paragraph><paragraph>Minimal = possible but difficult to ascertain whether there is slight elevation of plaque above normal skin, plus or minus surface dryness with some white coloration, plus or minus up to red coloration</paragraph></td></tr></tbody></table>","<table ID=\"Table17\" width=\"100%\"><caption>Table 17: Efficacy Results at 16 Weeks in Study Ps-II Number of Subjects (%)</caption><col width=\"33%\"/><col width=\"33%\"/><col width=\"33%\"/><tbody><tr><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Adalimumab 40 mg every other week</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Placebo</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>N = 99</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>N = 48</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>PGA: <content styleCode=\"italics\">Clear </content>or <content styleCode=\"italics\">minimal</content>*</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>70 (71%)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>5 (10%)</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>PASI 75</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>77 (78%)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>9 (19%)</paragraph></td></tr><tr><td colspan=\"3\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>* Clear = no plaque elevation, no scale, plus or minus hyperpigmentation or diffuse pink or red coloration</paragraph><paragraph>Minimal = possible but difficult to ascertain whether there is slight elevation of plaque above normal skin, plus or minus surface dryness with some white coloration, plus or minus up to red coloration</paragraph></td></tr></tbody></table>","<table ID=\"_Ref180066332\" width=\"100%\"><caption>Table 18: Efficacy Results at 26 Weeks</caption><col width=\"33%\"/><col width=\"33%\"/><col width=\"33%\"/><tbody><tr><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Endpoint</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Adalimumab 40 mg</paragraph><paragraph>every other week* N=109</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Placebo N=108</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>PGA-F: &#x2265;2-grade improvement and</paragraph><paragraph><content styleCode=\"italics\">clear </content>or <content styleCode=\"italics\">minimal</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>49%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>7%</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>mNAPSI 75</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>47%</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>3%</paragraph></td></tr><tr><td colspan=\"3\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>*Subjects received 80 mg of adalimumab at Week 0, followed by 40 mg every other week starting at Week 1.</paragraph></td></tr></tbody></table>","<table ID=\"_Ref180066384\" width=\"100%\"><caption>Table 19: Efficacy Results at 12 Weeks in Subjects with Moderate to Severe Hidradenitis Suppurativa</caption><col width=\"20%\"/><col width=\"20%\"/><col width=\"20%\"/><col width=\"20%\"/><col width=\"20%\"/><tbody><tr><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"/><td colspan=\"2\" align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">HS Study I</content></paragraph></td><td colspan=\"2\" align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">HS Study II*</content></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Placebo</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Adalimumab 40 mg Weekly</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Placebo</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Adalimumab 40 mg Weekly</content></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Hidradenitis Suppurativa Clinical Response (HiSCR)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>N = 154</paragraph><paragraph>40 (26%)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>N = 153</paragraph><paragraph>64 (42%)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>N=163</paragraph><paragraph>45 (28%)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>N=163</paragraph><paragraph>96 (59%)</paragraph></td></tr><tr><td colspan=\"5\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>*19.3% of subjects in Study HS-II continued baseline oral antibiotic therapy during the study.</paragraph></td></tr></tbody></table>","<table ID=\"_Ref180066433\" width=\"100.08%\"><caption>Table 20: Time to Treatment Failure in Studies UV I and UV II</caption><col width=\"14%\"/><col width=\"14%\"/><col width=\"16%\"/><col width=\"13%\"/><col width=\"14%\"/><col width=\"16%\"/><col width=\"13%\"/><tbody><tr><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Placebo</paragraph><paragraph>(N = 107)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>ADALIMUMAB (N = 110)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>HR</paragraph><paragraph>[95% CI]<sup>a</sup></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Placebo</paragraph><paragraph>(N = 111)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>ADALIMUMAB (N = 115)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>HR</paragraph><paragraph>[95% CI]<sup>a</sup></paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Failure<sup>b</sup> n (%)</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>84 (78.5)</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>60 (54.5)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.50</paragraph><paragraph>[0.36, 0.70]</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>61 (55.0)</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>45 (39.1)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>0.57</paragraph><paragraph>[0.39, 0.84]</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Median Time to Failure (Months) [95% CI]</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>3.0</paragraph><paragraph>[2.7, 3.7]</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>5.6</paragraph><paragraph>[3.9, 9.2]</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>N/A</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>8.3</paragraph><paragraph>[4.8, 12.0]</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NE<sup>c</sup></paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>N/A</paragraph></td></tr><tr><td colspan=\"7\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><sup>a </sup>HR of adalimumab versus placebo from proportional hazards regression with treatment as factor. </paragraph><paragraph><sup>b </sup>Treatment failure at or after Week 6 in Study UV I, or at or after Week 2 in Study UV II, was counted as event. Subjects who discontinued the study were censored at the time of dropping out. </paragraph><paragraph><sup>c </sup>NE = not estimable. Fewer than half of at-risk subjects had an event.</paragraph></td></tr></tbody></table>"],"nonclinical_toxicology":["13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies of adalimumab products have not been conducted to evaluate the carcinogenic potential or its effect on fertility."],"adverse_reactions_table":["<table ID=\"_Ref180064425\" width=\"100%\"><caption>Table 1: Adverse Reactions Reported by &#x2265;5% of Patients Treated with Adalimumab during Placebo-Controlled Period of Pooled RA Studies (Studies RA-I, RA-II, RA-III, and RA-IV)</caption><col width=\"33%\"/><col width=\"33%\"/><col width=\"33%\"/><tbody><tr><td valign=\"middle\" styleCode=\"Rrule Botrule Lrule Toprule \"/><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Adalimumab</paragraph><paragraph>40 mg subcutaneous Every Other Week</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Placebo</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Botrule \"/><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>(N=705)</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>(N=690)</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Adverse Reaction (Preferred Term)</paragraph></td><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Respiratory</content></paragraph></td><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Upper respiratory infection</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>17%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>13%</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Sinusitis</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>11%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>9%</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Flu syndrome</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>7%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>6%</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Gastrointestinal</content></paragraph></td><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Nausea</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>9%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>8%</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Abdominal pain</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>7%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>4%</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Laboratory Tests*</content></paragraph></td><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Laboratory test abnormal</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>8%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>7%</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Hypercholesterolemia</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>6%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>4%</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Hyperlipidemia</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>7%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>5%</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Hematuria</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>5%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>4%</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Alkaline phosphatase increased</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>5%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>3%</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Other</content></paragraph></td><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"/><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Headache</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>12%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>8%</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Rash</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>12%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>6%</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Accidental injury</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>10%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>8%</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Injection site reaction **</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>8%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>1%</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Back pain</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>6%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>4%</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Urinary tract infection</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>8%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>5%</paragraph></td></tr><tr><td valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph> Hypertension</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>5%</paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>3%</paragraph></td></tr><tr><td colspan=\"3\" valign=\"middle\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>* Laboratory test abnormalities were reported as adverse reactions in European trials</paragraph><paragraph>** Does not include injection site erythema, itching, hemorrhage, pain or swelling</paragraph></td></tr></tbody></table>","<table ID=\"_Ref180064608\" width=\"100%\" cellpadding=\"0pt\"><caption>Table 2: Anti-Adalimumab Antibody Development Determined by ELISA and ECL Assay in Patients Treated with adalimumab</caption><col width=\"14%\"/><col width=\"19%\"/><col width=\"10%\"/><col width=\"16%\"/><col width=\"20%\"/><col width=\"22%\"/><tbody><tr><td rowspan=\"2\" colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Indications</content></paragraph></td><td rowspan=\"2\" align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Study Duration</content></paragraph></td><td colspan=\"2\" align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Anti-Adalimumab Antibody Incidence by ELISA (n/N)</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Anti-Adalimumab Antibody Incidence by ECL Assay (n/N)</content></paragraph></td></tr><tr><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>In all patients who received adalimumab</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>In patients with serum adalimumab concentrations</paragraph><paragraph>&lt; 2 mcg/mL</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Rheumatoid Arthritis <sup>a</sup></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>6 to 12 months</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>5% (58/1062)</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NR</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NA</paragraph></td></tr><tr><td rowspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Toprule \"><paragraph>Juvenile Idiopathic Arthritis (JIA)</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>4 to 17 years of age <sup>b</sup></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>48 weeks</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>16% (27/171)</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NR</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NA</paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>2 to 4 years of age or &#x2265; 4 years of age and weighing &lt; 15 kg</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>24 weeks</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>7% (1/15) <sup>c</sup></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NR</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NA</paragraph></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Psoriatic Arthritis <sup>d</sup></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>48 weeks <sup>e</sup></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>13% (24/178)</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NR</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NA</paragraph></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Ankylosing Spondylitis</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>24 weeks</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>9% (16/185)</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NR</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NA</paragraph></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Adult Crohn&#x2019;s Disease</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>56 weeks</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>3% (7/269)</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>8% (7/86)</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NA</paragraph></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Pediatric Crohn&#x2019;s Disease</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>52 weeks</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>3% (6/182)</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>10% (6/58)</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NA</paragraph></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Adult Ulcerative Colitis</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>52 weeks</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>5% (19/360)</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>21% (19/92)</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NA</paragraph></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Plaque Psoriasis <sup>f</sup></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Up to 52 weeks <sup>g</sup></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>8% (77/920)</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>21% (77/372)</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>NA</paragraph></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Hidradenitis Suppurativa</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>36 weeks</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>7% (30/461)</paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>28% (58/207) <sup>h</sup></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>61% (272/445) <sup>i</sup></paragraph></td></tr><tr><td colspan=\"2\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Non-infectious Uveitis</paragraph></td><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>52 weeks</paragraph></td><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>5% (12/249)</paragraph></td><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>21% (12/57)</paragraph></td><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>40% (99/249) <sup>j</sup></paragraph></td></tr></tbody></table>"],"information_for_patients":["17 PATIENT COUNSELING INFORMATION Advise the patient or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Infections Inform patients that IDACIO may lower the ability of their immune system to fight infections. Instruct patients of the importance of contacting their doctor if they develop any symptoms of infection, including tuberculosis, invasive fungal infections, and reactivation of hepatitis B virus infections [see Warnings and Precautions ( 5.1 , 5.2 , 5.4 )] . Malignancies Counsel patients about the risk of malignancies while receiving IDACIO [see Warnings and Precautions ( 5.2 )] Hypersensitivity Reactions Advise patients to seek immediate medical attention if they experience any symptoms of severe hypersensitivity reactions. Other Medical Conditions Advise patients to report any signs of new or worsening medical conditions such as congestive heart failure, neurological disease, autoimmune disorders, or cytopenias. Advise patients to report any symptoms suggestive of a cytopenia such as bruising, bleeding, or persistent fever [see Warnings and Precautions ( 5.5 , 5.6 , 5.8 , 5.9 )] . Instructions on Injection Technique Inform patients that the first injection is to be performed under the supervision of a qualified health care professional. If a patient or caregiver is to administer IDACIO, instruct them in injection techniques and assess their ability to inject subcutaneously to ensure the proper administration of IDACIO [see Instructions for Use ]. For patients who will use the IDACIO Pen, tell them to: • Remove the needle cap of the Pen and push and hold the Pen firmly against the skin on the chosen injection site. • Activate Pen by pressing the injection button. The click means the start of the injection. • Keep holding the IDACIO Pen against their skin until the injection has finished. • Will know that the injection has finished when the syringe plunger moves all the way down to the bottom of the transparent syringe housing to enable the safety guard to cover the needle Instruct patients to dispose of their used needles and syringes or used Pen in a FDA-cleared sharps disposal container immediately after use. Instruct patients not to dispose of loose needles and syringes or Pens in their household trash. Instruct patients that if they do not have a FDA-cleared sharps disposal container, they may use a household container that is made of a heavy-duty plastic, can be closed with a tight-fitting and puncture-resistant lid without sharps being able to come out, upright and stable during use, leak-resistant, and properly labeled to warn of hazardous waste inside the container. Instruct patients that when their sharps disposal container is almost full, they will need to follow their community guidelines for the correct way to dispose of their sharps disposal container. Instruct patients that there may be state or local laws regarding disposal of used needles and syringes. Refer patients to the FDA’s website at http://www.fda.gov/safesharpsdisposal for more information about safe sharps disposal, and for specific information about sharps disposal in the state that they live in. Instruct patients not to dispose of their used sharps disposal container in their household trash unless their community guidelines permit this. Instruct patients not to recycle their used sharps disposal container. Manufactured by: Fresenius Kabi USA, LLC Lake Zurich, IL 60047, U.S.A US License Number 2146"],"dosage_and_administration":["2 DOSAGE AND ADMINISTRATION • Administer by subcutaneous injection ( 2 ) Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis ( 2.1 ): • Adults: 40 mg every other week. • Some patients with RA not receiving methotrexate may benefit from increasing the dosage to 40 mg every week or 80 mg every other week. Juvenile Idiopathic Arthritis ( 2.2 ): Pediatric Weight 2 Years of Age and Older Recommended Dosage 10 kg (22 lbs) to less than 15 kg (33 lbs) 10 mg every other week 15 kg (33 lbs) to less than 30 kg (66 lbs) 20 mg every other week 30 kg (66 lbs) and greater 40 mg every other week • Administer by subcutaneous injection ( 2 ) Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis ( 2.1 ): • Adults: 40 mg every other week. o Some patients with RA not receiving methotrexate may benefit from increasing the dosage to 40 mg every week or 80 mg every other week. Juvenile Idiopathic Arthritis ( 2.2 ): Pediatric Weight 2 Years of Age and Older Recommended Dosage 10 kg (22 lbs) to less than 15 kg (33 lbs) 10 mg every other week 15 kg (33 lbs) to less than 30 kg (66 lbs) 20 mg every other week 30 kg (66 lbs) and greater 40 mg every other week Crohn's Disease ( 2.3 ) • Adults: 160 mg on Day 1 (given in one day or split over two consecutive days); 80 mg on Day 15; and 40 mg every other week starting on Day 29. • Pediatric Patients 6 Years of Age and Older : Pediatric Weight Recommended Dosage Days 1 and 15 Starting on Day 29 17 kg (37 lbs) to less than 40 kg (88 lbs) Day 1: 80 mg Day 15: 40 mg 20 mg every other week 40 kg (88 lbs) and greater Day 1: 160 mg (single dose or split over two consecutive days) Day 15: 80 mg 40 mg every other week Ulcerative Colitis ( 2.4 ): • Adults: 160 mg on Day 1 (given in one day or split over two consecutive days), 80 mg on Day 15 and 40 mg every other week starting on Day 29. Discontinue in patients without evidence of clinical remission by eight weeks (Day 57). Plaque Psoriasis or Adult Uveitis ( 2.5 ): • Adults: 80 mg initial dose, followed by 40 mg every other week starting one week after initial dose. Hidradenitis Suppurativa ( 2.6 ): • Adults: o Day 1: 160 mg (given in one day or split over two consecutive days) o Day 15: 80 mg o Day 29 and subsequent doses: 40 mg every week or 80 mg every other week 2.1 Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis The recommended subcutaneous dosage of IDACIO for adult patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) is 40 mg administered every other week. Methotrexate (MTX), other non-biologic DMARDS, glucocorticoids, nonsteroidal anti- inflammatory drugs (NSAIDs), and/or analgesics may be continued during treatment with IDACIO. In the treatment of RA, some patients not taking concomitant MTX may derive additional benefit from increasing the dosage of IDACIO to 40 mg every week or 80 mg every other week. 2.2 Juvenile Idiopathic Arthritis The recommended subcutaneous dosage of IDACIO for patients 2 years of age and older with polyarticular juvenile idiopathic arthritis (JIA) is based on weight as shown below. MTX, glucocorticoids, NSAIDs, and/or analgesics may be continued during treatment with IDACIO. Pediatric Weight (2 Years of Age and older) Recommended Dosage 10 kg (22 lbs) to less than 15 kg (33 lbs) 10 mg every other week 15 kg (33 lbs) to less than 30 kg (66 lbs) 20 mg every other week 30 kg (66 lbs) and greater 40 mg every other week The only dosage form for IDACIO that allows weight-based dosing for pediatric patients below 30 kg is the single-dose glass vial kit for institutional use only. Adalimumab products have not been studied in patients with polyarticular JIA less than 2 years of age or in patients with a weight below 10 kg. 2.3 Crohn’s Disease Adults The recommended subcutaneous dosage of IDACIO for adult patients with Crohn’s disease (CD) is 160 mg initially on Day 1 (given in one day or split over two consecutive days), followed by 80 mg two weeks later (Day 15). Two weeks later (Day 29) begin a dosage of 40 mg every other week. Aminosalicylates and/or corticosteroids may be continued during treatment with IDACIO. Azathioprine, 6-mercaptopurine (6-MP) [see Warnings and Precautions ( 5.2 )] or MTX may be continued during treatment with IDACIO if necessary. Pediatrics The recommended subcutaneous dosage of IDACIO for pediatric patients 6 years of age and older with Crohn’s disease (CD) is based on body weight as shown below: Pediatric Weight Recommended Dosage Days 1 through 15 Starting on Day 29 17 kg (37 lbs) to less than 40 kg (88 lbs) Day 1: 80 mg Day 15: 40 mg 20 mg every other week 40 kg (88 lbs) and greater Day 1: 160 mg (single dose or split over two consecutive days) Day 15: 80 mg 40 mg every other week The only dosage form for IDACIO that allows weight-based dosing for pediatric patients below 40 kg is the single-dose glass vial kit for institutional use only 2.4 Ulcerative Colitis Adults The recommended subcutaneous dosage of IDACIO for adult patients with ulcerative colitis is 160 mg initially on Day 1 (given in one day or split over two consecutive days), followed by 80 mg two weeks later (Day 15). Two weeks later (Day 29) continue with a dosage of 40 mg every other week. Discontinue IDACIO in adult patients without evidence of clinical remission by eight weeks (Day 57) of therapy. Aminosalicylates and/or corticosteroids may be continued during treatment with IDACIO. Azathioprine and 6-mercaptopurine (6-MP) [ see Warnings and Precautions (5.2) ] may be continued during treatment with IDACIO if necessary. 2.5 Plaque Psoriasis or Adult Uveitis The recommended subcutaneous dosage of IDACIO for adult patients with plaque psoriasis (Ps) or Uveitis (UV) is an initial dose of 80 mg, followed by 40 mg given every other week starting one week after the initial dose. The use of adalimumab products in moderate to severe chronic Ps beyond one year has not been evaluated in controlled clinical studies. 2.6 Hidradenitis Suppurativa Adults The recommended subcutaneous dosage of IDACIO for adult patients with hidradenitis suppurativa (HS) is an initial dose of 160 mg (given in one day or split over two consecutive days), followed by 80 mg two weeks later (Day 15). Begin 40 mg weekly or 80 mg every other week dosing two weeks later (Day 29). 2.7 Monitoring to Assess Safety Prior to initiating IDACIO and periodically during therapy, evaluate patients for active tuberculosis and test for latent infection [see Warnings and Precautions ( 5.1 )] . 2.8 General Considerations for Administration IDACIO Pen or prefilled syringe is intended for use under the guidance and supervision of a physician. A patient may self-inject IDACIO or a caregiver may inject IDACIO using either the IDACIO Pen or prefilled syringe if a physician determines that it is appropriate, and with medical follow-up, as necessary, after proper training in subcutaneous injection technique. IDACIO may be taken out of the refrigerator for 15 to 30 minutes before injecting to allow the liquid to come to room temperature. Do not remove the cap or cover while allowing it to reach room temperature. Carefully inspect the solution in the IDACIO Pen, or prefilled syringe or single dose institutional use vial for particulate matter and discoloration prior to subcutaneous administration. If particulates and discolorations are noted, do not use the product. IDACIO does not contain preservatives. Therefore, discard unused portions of drug remaining in the syringe. Instruct patients using the IDACIO Pen or prefilled syringe to inject the full amount in the syringe, according to the directions provided in the Instructions for Use [see Instructions for Use ]. Injections should occur at separate sites in the thigh or abdomen. Rotate injection sites and do not give injections into areas where the skin is tender, bruised, red or hard. If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time. The IDACIO syringe plunger stopper and needle cover are not made with natural rubber latex. The IDACIO single-dose institutional use vial kit is for administration within an institutional setting only, such as a hospital, physician’s office, or clinic. Withdraw the dose using the vial adapter, the sterile syringe and needle provided. Only administer one dose per vial. The vial does not contain preservatives; discard unused portion. The IDACIO vial and syringe stopper are not made with natural rubber latex. Read these Administration Instructions before using the Idacio Vial kit. IDACIO is supplied in a carton containing 1 sterile single-use syringe, 1 sterile needle, 1 vial adapter, 2 alcohol preps and 1 glass vial providing 40 mg/0.8 mL of IDACIO ( Figure A ) The contents of the Idacio Vial Kit are for single-dose (one-time) use only. Discard unused portion. Figure A Prior to Administration • Remove the Idacio Vial Kit from the refrigerator and let it sit at room temperature for at least 30 minutes. • Check the expiration date. • Remove Vial Kit contents from the carton and inspect for damage. Do not use if any kit component or packaging has been damaged. • Check the vial contents to make sure that the liquid is clear, colorless, and free of particles and flakes. Note : Prepare syringe just prior to administration and inject immediately. Do not store Idacio in the syringe. Step 1: Prepare Vial and Vial Adapter 1.1 Remove plastic flip off cap from vial and disinfect the rubber stopper. Do not touch the top of the vial after cleaning 1.2 Without removing the vial adapter from its packaging, peel off the top cover (Figure B). Do not touch the vial adapter Figure B 1.3 With the vial adapter still in its packaging, push the vial adapter onto the vial top until it snaps in place (Figure C). Figure C 1.4 Remove the vial adapter packaging (Figure D). Figure D Step 2: Connect Syringe to Vial Adapter 2.1 Remove syringe from outer packaging. Do not touch the syringe tip. Figure E 2.2 Hold the base of the vial adapter and connect the syringe to the vial adapter by turning it clockwise (Figure E). Step 3: Withdraw the Dose 3.1 Invert the vial completely with the vial adapter and syringe still connected (Figure F). Figure F 3.2 Slowly withdraw the prescribed dose of Idacio into the syringe for administration (Figure G). Remove air bubbles from the syringe. Do not pull the plunger rod out. Figure G Step 4: Disconnect the syringe 4.1 Turn over the vial and syringe. Hold the base of the vial adapter and disconnect the syringe from the vial adapter by turning it counterclockwise (Figure H). Do not touch the syringe tip Figure H Step 5: Attach Needle Figure I 5.1 Peel open the outer needle packaging to uncover the yellow syringe connector (Figure J). Figure J 5.2 Insert the syringe tip into the syringe connector. Turn the syringe connector in a clockwise direction to tighten (Figure K). Figure K 5.3 Pull the outer needle packaging off (Figure L). Do not remove the clear needle cap. Figure L 5.4 Pull back the needle safety cover toward the syringe (Figure M). Do not remove the needle cover from the connector. Figure M Step 6: Administer medication 6.1 When you are ready to inject Idacio remove the clear needle cap by pulling it straight off and throw it away (Figure N). Do not recap the needle. Figure N 6.2 Administer the dose subcutaneously. 6.3 Place your thumb or index finger on the center of the textured finger pad and push the pink needle safety cover forward over the needle until you hear it click or feel it lock (Figure O). Figure O Step 7: Discard Used Syringe and Needle 7.1 Discard used syringe and needle into an appropriate sharps container. adali-img-01.jpg adali-img-02.jpg adali-img-03.jpg adali-img-04.jpg adali-img-05.jpg adali-img-06.jpg adali-img-07.jpg adali-img-08.jpg adali-img-09.jpg adali-img-10.jpg adali-img-11.jpg adali-img-12.jpg adali-img-13.jpg adali-img-14.jpg adali-img-15.jpg"],"spl_product_data_elements":["IDACIO adalimumab-aacf IDACIO adalimumab-aacf ADALIMUMAB ADALIMUMAB ACETIC ACID TREHALOSE DIHYDRATE POLYSORBATE 80 SODIUM CHLORIDE WATER SODIUM HYDROXIDE ISOPROPYL ALCOHOL isopropyl alcohol ISOPROPYL ALCOHOL ISOPROPYL ALCOHOL WATER"],"dosage_forms_and_strengths":["3 DOSAGE FORMS AND STRENGTHS IDACIO is a clear and colorless to pale yellow solution available as: • Pen (IDACIO Pen) Injection: 40 mg/0.8 mL in a single-dose pen. • Prefilled Syringe Injection: 40 mg/0.8 mL in a single-dose prefilled glass syringe. • Single-Dose Institutional Use Vial Kit Injection: 40 mg/0.8 mL in a single-dose, glass vial kit for institutional use only. Injection: • Single-dose prefilled pen (IDACIO Pen): 40 mg/0.8 mL ( 3 ) • Single-dose prefilled glass syringe: 40 mg/0.8 mL ( 3 ) • Single dose glass vial kit for institutional use only: 40 mg/0.8 mL ( 3 )"],"use_in_specific_populations":["8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Available studies with use of adalimumab during pregnancy do not reliably establish an association between adalimumab and major birth defects. Clinical data are available from the Organization of Teratology Information Specialists (OTIS)/MotherToBaby Pregnancy Registry in pregnant women with rheumatoid arthritis (RA) or Crohn’s disease (CD) treated with adalimumab. Registry results showed a rate of 10% for major birth defects with first trimester use of adalimumab in pregnant women with RA or CD and a rate of 7.5% for major birth defects in the disease-matched comparison cohort. The lack of pattern of major birth defects is reassuring and differences between exposure groups may have impacted the occurrence of birth defects (see Data ) . Adalimumab is actively transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in-utero exposed infant (see Clinical Considerations ) . In an embryo-fetal perinatal development study conducted in cynomolgus monkeys, no fetal harm or malformations were observed with intravenous administration of adalimumab during organogenesis and later in gestation, at doses that produced exposures up to approximately 373 times the maximum recommended human dose (MRHD) of 40 mg subcutaneous without methotrexate (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated maternal and embryo/fetal risk Published data suggest that the risk of adverse pregnancy outcomes in women with RA or inflammatory bowel disease (IBD) is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth. Fetal/Neonatal Adverse Reactions Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester ( see Data ) . Risks and benefits should be considered prior to administering live or live-attenuated vaccines to infants exposed to adalimumab products in utero [see Use in Specific Populations ( 8.4 )] . Data Human Data A prospective cohort pregnancy exposure registry conducted by OTIS/MotherToBaby in the U.S. and Canada between 2004 and 2016 compared the risk of major birth defects in live-born infants of 221 women (69 RA, 152 CD) treated with adalimumab during the first trimester and 106 women (74 RA, 32 CD) not treated with adalimumab. The proportion of major birth defects among live-born infants in the adalimumab-treated and untreated cohorts was 10% (8.7% RA, 10.5% CD) and 7.5% (6.8% RA, 9.4% CD), respectively. The lack of pattern of major birth defects is reassuring and differences between exposure groups may have impacted the occurrence of birth defects. This study cannot reliably establish whether there is an association between adalimumab and major birth defects because of methodological limitations of the registry, including small sample size, the voluntary nature of the study, and the non-randomized design. In an independent clinical study conducted in ten pregnant women with IBD treated with adalimumab, adalimumab concentrations were measured in maternal serum as well as in cord blood (n=10) and infant serum (n=8) on the day of birth. The last dose of adalimumab was given between 1 and 56 days prior to delivery. Adalimumab concentrations were 0.16-19.7 mcg/mL in cord blood, 4.28-17.7 mcg/mL in infant serum, and 0-16.1 mcg/mL in maternal serum. In all but one case, the cord blood concentration of adalimumab was higher than the maternal serum concentration, suggesting adalimumab actively crosses the placenta. In addition, one infant had serum concentrations at each of the following: 6 weeks (1.94 mcg/mL), 7 weeks (1.31 mcg/mL), 8 weeks (0.93 mcg/mL), and 11 weeks (0.53 mcg/mL), suggesting adalimumab can be detected in the serum of infants exposed in utero for at least 3 months from birth. Animal Data In an embryo-fetal perinatal development study, pregnant cynomolgus monkeys received adalimumab from gestation days 20 to 97 at doses that produced exposures up to 373 times that achieved with the MRHD without methotrexate (on an AUC basis with maternal IV doses up to 100 mg/kg/week). Adalimumab did not elicit harm to the fetuses or malformations. 8.2 Lactation Risk Summary Limited data from case reports in the published literature describe the presence of adalimumab in human milk at infant doses of 0.1% to 1% of the maternal serum concentration. Published data suggest that the systemic exposure to a breastfed infant is expected to be low because adalimumab is a large molecule and is degraded in the gastrointestinal tract. However, the effects of local exposure in the gastrointestinal tract are unknown. There are no reports of adverse effects of adalimumab products on the breastfed infant and no effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for IDACIO and any potential adverse effects on the breastfed child from IDACIO or from the underlying maternal condition. 8.4 Pediatric Use The safety and effectiveness of IDACIO have been established for: • reducing signs and symptoms of moderately to severely active polyarticular JIA in pediatric patients 2 years of age and older. • the treatment of moderately to severely active Crohn’s disease in pediatric patients 6 years of age and older. Pediatric assessments for IDACIO demonstrate that IDACIO is safe and effective for pediatric patients in indications for which HUMIRA (adalimumab) is approved. However, IDACIO is not approved for such indications due to marketing exclusivity for HUMIRA (adalimumab). Due to their inhibition of TNFα, adalimumab products administered during pregnancy could affect immune response in the in utero-exposed newborn and infant. Data from eight infants exposed to adalimumab in utero suggest adalimumab crosses the placenta [see Use in Specific Populations ( 8.1 )] . The clinical significance of elevated adalimumab concentrations in infants is unknown. The safety of administering live or live-attenuated vaccines in exposed infants is unknown. Risks and benefits should be considered prior to vaccinating (live or live-attenuated) exposed infants. Post-marketing cases of lymphoma, including hepatosplenic T-cell lymphoma and other malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blockers including adalimumab products [see Warnings and Precautions ( 5.2 )] . Juvenile Idiopathic Arthritis In Study JIA-I, adalimumab was shown to reduce signs and symptoms of active polyarticular JIA in patients 4 to 17 years of age [see Clinical Studies ( 14.2 )] . In Study JIA-II, the safety profile for patients 2 to <4 years of age was similar to the safety profile for patients 4 to 17 years of age with polyarticular JIA [see Adverse Reactions ( 6.1 )] . Adalimumab products have not been studied in patients with polyarticular JIA less than 2 years of age or in patients with a weight below 10 kg. The safety of adalimumab in patients in the polyarticular JIA trials was generally similar to that observed in adults with certain exceptions [see Adverse Reactions ( 6.1 )] . The safety and effectiveness of IDACIO have not been established in pediatric patients with JIA less than 2 years of age. Pediatric Crohn’s Disease The safety and effectiveness of IDACIO for the treatment of moderately to severely active Crohn’s disease have been established in pediatric patients 6 years of age and older. Use of IDACIO for this indication is supported by IDACIO’s approval as a biosimilar to adalimumab and evidence from adequate and well-controlled studies in adults with additional data of adalimumab from a randomized, double-blind, 52-week clinical study of two dose concentrations of adalimumab in 192 pediatric patients (6 years to 17 years of age) [see Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.2 , 12.3 ), Clinical Studies ( 14.6 )] . The adverse reaction profile in patients 6 years to 17 years of age was similar to adults. The safety and effectiveness of IDACIO have not been established in pediatric patients with Crohn’s disease less than 6 years of age. 8.5 Geriatric Use A total of 519 RA patients 65 years of age and older, including 107 patients 75 years of age and older, received adalimumab in clinical studies RA-I through IV. No overall difference in effectiveness was observed between these patients and younger patients. The frequency of serious infection and malignancy among adalimumab treated patients 65 years of age and older was higher than for those less than 65 years of age. Consider the benefits and risks of IDACIO in patients 65 years of age and older. In patients treated with IDACIO, closely monitor for the development of infection or malignancy [see Warnings and Precautions ( 5.1 , 5.2 )] ."],"dosage_and_administration_table":["<table width=\"100%\" cellpadding=\"0pt\"><col width=\"41%\"/><col width=\"59%\"/><tbody><tr><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Pediatric Weight 2 Years of Age and Older</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Recommended Dosage</content></paragraph></td></tr><tr><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph>10 kg (22 lbs) to less than 15 kg (33 lbs)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>10 mg every other week</paragraph></td></tr><tr><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph>15 kg (33 lbs) to less than 30 kg (66 lbs)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>20 mg every other week</paragraph></td></tr><tr><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>30 kg (66 lbs) and greater</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>40 mg every other week</paragraph></td></tr></tbody></table>","<table width=\"100%\" cellpadding=\"0pt\"><col width=\"41%\"/><col width=\"59%\"/><tbody><tr><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Pediatric Weight 2 Years of Age and Older</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Recommended Dosage</content></paragraph></td></tr><tr><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph>10 kg (22 lbs) to less than 15 kg (33 lbs)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>10 mg every other week</paragraph></td></tr><tr><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph>15 kg (33 lbs) to less than 30 kg (66 lbs)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>20 mg every other week</paragraph></td></tr><tr><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>30 kg (66 lbs) and greater</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>40 mg every other week</paragraph></td></tr></tbody></table>","<table width=\"100%\" cellpadding=\"0pt\"><col width=\"26%\"/><col width=\"44%\"/><col width=\"31%\"/><tbody><tr><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Pediatric Weight</content></paragraph></td><td colspan=\"2\" align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Recommended Dosage</content></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"/><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Days 1 and 15</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Starting on Day 29</content></paragraph></td></tr><tr><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph>17 kg (37 lbs) to less than 40 kg (88 lbs)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>Day 1: 80 mg Day 15: 40 mg</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph>20 mg every other week</paragraph></td></tr><tr><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>40 kg (88 lbs) and greater</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Day 1: 160 mg (single dose or split over two consecutive days) Day 15: 80 mg</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>40 mg every other week</paragraph></td></tr></tbody></table>","<table width=\"100%\"><col width=\"50%\"/><col width=\"50%\"/><tbody><tr><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Pediatric Weight (2 Years of Age and older)</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Recommended Dosage</paragraph></td></tr><tr><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">10 kg (22 lbs) to less than 15 kg (33 lbs)</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"xmChange\">10 mg every other week</content></paragraph></td></tr><tr><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">15 kg (33 lbs) to less than 30 kg (66 lbs)</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"xmChange\">20 mg every other week</content></paragraph></td></tr><tr><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>30 kg (66 lbs) and greater</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>40 mg every other week</paragraph></td></tr></tbody></table>","<table width=\"100%\" styleCode=\"Noautorules\"><col width=\"33%\"/><col width=\"33%\"/><col width=\"33%\"/><tbody><tr><td rowspan=\"2\" align=\"center\" valign=\"middle\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Pediatric Weight</content></paragraph></td><td colspan=\"2\" align=\"center\" valign=\"middle\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"bold\">Recommended Dosage</content></paragraph></td></tr><tr><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Days 1 through 15</content></paragraph></td><td align=\"center\" valign=\"middle\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"bold\">Starting on Day 29</content></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">17 kg (37 lbs) to less than 40 kg (88 lbs)</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"xmChange\">Day 1: 80 mg</content></paragraph><paragraph><content styleCode=\"xmChange\">Day 15: 40 mg</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><paragraph><content styleCode=\"xmChange\">20 mg every other week</content></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>40 kg (88 lbs) and greater</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>Day 1: 160 mg (single dose or split over two consecutive days)</paragraph><paragraph>Day 15: 80 mg</paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph>40 mg every other week</paragraph></td></tr></tbody></table>","<table width=\"100%\" styleCode=\"Noautorules\"><col width=\"43%\"/><col width=\"57%\"/><tbody><tr><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"xmChange\">Step 1: Prepare Vial and Vial Adapter</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"/></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">1.1 Remove plastic flip off cap from vial and disinfect the rubber stopper. Do not touch the top of the vial after cleaning</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">1.2 Without removing the vial adapter from its packaging, peel off the top cover (Figure B). Do not touch the vial adapter</content></paragraph></td><td align=\"center\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><renderMultiMedia referencedObject=\"ID_7bbcfeaa-9382-4b04-ab72-41ba9a72d780\" ID=\"id-1240317901\"><caption>Figure B</caption></renderMultiMedia></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">1.3 With the vial adapter still in its packaging, push the vial adapter onto the vial top until it snaps in place (Figure C).</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><renderMultiMedia referencedObject=\"ID_0e6b44b5-174a-4d61-8b37-5140afbf2edb\" ID=\"id-570963362\"><caption>Figure C</caption></renderMultiMedia></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">1.4 Remove the vial adapter packaging (Figure D).</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><renderMultiMedia referencedObject=\"ID_431566fa-759a-461c-b78d-d996ca2980ac\" ID=\"id-650217541\"><caption>Figure D</caption></renderMultiMedia></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">Step 2: Connect Syringe to Vial Adapter</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">2.1 Remove syringe from outer packaging. Do not touch the syringe tip.</content></paragraph></td><td rowspan=\"2\" valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><renderMultiMedia referencedObject=\"ID_95930108-e57a-497d-87af-ea9d50a63b15\" ID=\"id-1405445738\"><caption>Figure E</caption></renderMultiMedia></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">2.2 Hold the base of the vial adapter and connect the syringe to the vial adapter by turning it clockwise (Figure E).</content></paragraph></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">Step 3: Withdraw the Dose</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">3.1 Invert the vial completely with the vial adapter and syringe still connected (Figure F).</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><renderMultiMedia referencedObject=\"ID_90579b9c-0e71-40d0-a0be-219e1d0c5353\" ID=\"id1746374524\"><caption>Figure F</caption></renderMultiMedia></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">3.2 Slowly withdraw the prescribed dose of Idacio into the syringe for administration (Figure G). Remove air bubbles from the syringe. Do not pull the plunger rod out.</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><renderMultiMedia referencedObject=\"B135A634-AC96-4B91-921C-3CD30387E5C8\" ID=\"id-419406638\"><caption>Figure G</caption></renderMultiMedia></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">Step 4: Disconnect the syringe</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">4.1 Turn over the vial and syringe. Hold the base of the vial adapter and disconnect the syringe from the vial adapter by turning it counterclockwise (Figure H). Do not touch the syringe tip</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><renderMultiMedia referencedObject=\"B6BA423D-F458-4C90-9170-8EE1AD0D095D\" ID=\"id1137758094\"><caption>Figure H</caption></renderMultiMedia></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">Step 5: Attach Needle </content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><renderMultiMedia referencedObject=\"ID_1af77eec-8318-4d6b-9a71-2b391e474865\" ID=\"id-209961524\"><caption>Figure I</caption></renderMultiMedia></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">5.1 Peel open the outer needle packaging to uncover the yellow syringe connector (Figure J).</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><renderMultiMedia referencedObject=\"ID_776ceb9c-c4a4-4942-85dc-1b01c26f845b\" ID=\"id-92398792\"><caption>Figure J</caption></renderMultiMedia></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">5.2 Insert the syringe tip into the syringe connector. Turn the syringe connector in a clockwise direction to tighten (Figure K).</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><renderMultiMedia referencedObject=\"ID_17f726a7-27fb-4359-b554-0a5dc90e3d76\" ID=\"id-1856103405\"><caption>Figure K</caption></renderMultiMedia></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">5.3 Pull the outer needle packaging off (Figure L). Do not remove the clear needle cap.</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><renderMultiMedia referencedObject=\"ID_2faa72f4-f06f-495d-a56a-3d34943bca34\" ID=\"id1625029574\"><caption>Figure L</caption></renderMultiMedia></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">5.4 Pull back the needle safety cover toward the syringe (Figure M). Do not remove the needle cover from the connector.</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><renderMultiMedia referencedObject=\"ID_3cfbff37-9586-4e4a-98df-ef2dacd476a5\" ID=\"id1525288027\"><caption>Figure M</caption></renderMultiMedia></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">Step 6: Administer medication</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">6.1 When you are ready to inject Idacio remove the clear needle cap by pulling it straight off and throw it away (Figure N). Do not recap the needle.</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><renderMultiMedia referencedObject=\"E8DA11D1-6C19-4C5F-BA84-BF0573976738\" ID=\"id1461450882\"><caption>Figure N</caption></renderMultiMedia></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">6.2 Administer the dose subcutaneously.</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">6.3 Place your thumb or index finger on the center of the textured finger pad and push the pink needle safety cover forward over the needle until you hear it click or feel it lock (Figure O).</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"><renderMultiMedia referencedObject=\"ID_639b2564-66ac-4811-88a2-32c4ea8968e7\" ID=\"id-58325166\"><caption>Figure O</caption></renderMultiMedia></td></tr><tr><td valign=\"top\" styleCode=\"Rrule Lrule Botrule \"><paragraph><content styleCode=\"xmChange\">Step 7: Discard Used Syringe and Needle</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Lrule Toprule Botrule \"/></tr><tr><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"><paragraph><content styleCode=\"xmChange\">7.1 Discard used syringe and needle into an appropriate sharps container.</content></paragraph></td><td valign=\"top\" styleCode=\"Rrule Botrule Lrule Toprule \"/></tr></tbody></table>"],"package_label_principal_display_panel":["Principal Display Panel –40 mg/ 0.8 mL Single-Dose Institutional Use-Carton-Label Idacio ® adalimumab-aacf Injection 40mg/ 0.8mL NDC 65219-558-08 Rx Only For subcutaneous Use Only Single-dose vial kit Discard Unused Portion Carton contains: For Institutional Use Only 1 Single-dose vial 1 Sterile single-use syringe 1. Sterile needle 1 Vial adapter 2 Alcohol preps 1 Prescribing information 1 Medication guide FRESENIUS KABI label-pdpimage","Principal Display Panel –40 mg/ 0.8 mL Single-Dose Institutional Use-Vial-Label Idacio ® 40mg/ 0.8mL NDC 65219-562-01 adalimumab-aacf Injection For subcutaneous Use Only EXP: Lot: US License No. 2146 Fresenius Kabi USA, LLC adali-label-02.jpg"],"carcinogenesis_and_mutagenesis_and_impairment_of_fertility":["13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies of adalimumab products have not been conducted to evaluate the carcinogenic potential or its effect on fertility."]},"tags":[{"label":"Tumor Necrosis Factor Blocker","category":"class"},{"label":"Monoclonal Antibody","category":"modality"},{"label":"Tumor necrosis factor","category":"target"},{"label":"L04AB04","category":"atc"},{"label":"Intravenous, Subcutaneous","category":"route"},{"label":"Ankylosing spondylitis","category":"indication"},{"label":"Axial spondyloarthritis","category":"indication"},{"label":"Behcet's disease","category":"indication"},{"label":"Crohn's disease","category":"indication"},{"label":"Hidradenitis suppurativa","category":"indication"},{"label":"Juvenile idiopathic arthritis","category":"indication"},{"label":"Abbvie Inc","category":"company"},{"label":"Anti-Inflammatory Agents","category":"pharmacology"},{"label":"Antirheumatic Agents","category":"pharmacology"},{"label":"Tumor Necrosis Factor Inhibitors","category":"pharmacology"}],"phase":"marketed","safety":{"boxedWarnings":["WARNING: SERIOUS INFECTIONS and MALIGNANCY SERIOUS INFECTIONS Patients treated with adalimumab products including IDACIO are at increased risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions ( 5.1 )] . Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue IDACIO if a patient develops a serious infection or sepsis. Reported infections include: • Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Test patients for latent TB before IDACIO use and during therapy. Initiate treatment for latent TB prior to IDACIO use. • Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric anti- fungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness. • Bacterial, viral and other infections due to opportunistic pathogens, including Legionella and Listeria. Carefully consider the risks and benefits of treatment with IDACIO prior to initiating therapy in patients with chronic or recurrent infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with IDACIO, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )] . MALIGNANCY Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers including adalimumab products [see Warnings and Precautions ( 5.2 )] . Post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers including adalimumab products. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn's disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all these patients had received treatment with azathioprine or 6‑mercaptopurine (6–MP) concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants [see Warnings and Precautions ( 5.2 )] WARNING: SERIOUS INFECTIONS and MALIGNANCY See full prescribing information for complete boxed warning. SERIOUS INFECTIONS ( 5.1 , 6.1 ): • Increased risk of serious infections leading to hospitalization or death, including tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as histoplasmosis), and infections due to other opportunistic pathogens. • Discontinue IDACIO if a patient develops a serious infection or sepsis during treatment. • Perform test for latent TB; if positive, start treatment for TB prior to starting IDACIO. • Monitor all patients for active TB during treatment, even if initial latent TB test is negative. MALIGNANCY ( 5.2 ): • Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers including adalimumab products. • Post-marketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have occurred in adolescent and young adults with inflammatory bowel disease treated with TNF blockers including adalimumab products."],"safetySignals":[{"date":"","signal":"DRUG INEFFECTIVE","source":"FDA FAERS","actionTaken":"92349 reports"},{"date":"","signal":"PAIN","source":"FDA FAERS","actionTaken":"50157 reports"},{"date":"","signal":"ARTHRALGIA","source":"FDA FAERS","actionTaken":"49196 reports"},{"date":"","signal":"INJECTION SITE PAIN","source":"FDA FAERS","actionTaken":"48080 reports"},{"date":"","signal":"FATIGUE","source":"FDA FAERS","actionTaken":"40232 reports"},{"date":"","signal":"RHEUMATOID ARTHRITIS","source":"FDA FAERS","actionTaken":"36291 reports"},{"date":"","signal":"HEADACHE","source":"FDA FAERS","actionTaken":"29038 reports"},{"date":"","signal":"NAUSEA","source":"FDA FAERS","actionTaken":"27690 reports"},{"date":"","signal":"DIARRHOEA","source":"FDA FAERS","actionTaken":"26317 reports"},{"date":"","signal":"RASH","source":"FDA FAERS","actionTaken":"25752 reports"}],"drugInteractions":[{"drug":"Abatacept","severity":"Serious","mechanism":"Combination of TNF blockers with abatacept increases risk of serious infection","management":"Use of IDACIO with abatacept is not recommended in patients with RA","clinicalEffect":"Increased risk of serious infection with no added benefit"},{"drug":"Anakinra","severity":"Serious","mechanism":"Combination of TNF blockers with anakinra increases risk of serious infection","management":"Use of IDACIO with anakinra is not recommended in patients with RA","clinicalEffect":"Increased risk of serious infection with no added benefit"},{"drug":"Live vaccines","severity":"Serious","mechanism":"TNF blocker may impair immune response to live vaccines","management":"Avoid the use of live vaccines with IDACIO","clinicalEffect":"Potential vaccine failure or adverse effects"},{"drug":"Methotrexate (MTX)","severity":"Moderate","mechanism":"MTX reduces apparent adalimumab clearance","management":"Data do not suggest the need for dose adjustment of either IDACIO or MTX","clinicalEffect":"Increased adalimumab concentrations"},{"drug":"CYP450 substrates with narrow therapeutic index","severity":"Moderate","mechanism":"Adalimumab may influence formation of CYP450 enzymes by antagonizing cytokine activity","management":"Monitor effect (e.g., warfarin) upon initiation or discontinuation of IDACIO","clinicalEffect":"Potential changes in substrate metabolism and efficacy"}],"commonSideEffects":[{"effect":"Nasopharyngitis","drugRate":"7.5%","organSystem":"Infections and infestations","placeboRate":"","totalAtRisk":159,"totalAffected":12,"trialsReporting":1},{"effect":"Injection site erythema","drugRate":"3.1%","organSystem":"General disorders","placeboRate":"","totalAtRisk":159,"totalAffected":5,"trialsReporting":1},{"effect":"HEADACHE","drugRate":"12.5%","organSystem":"Nervous system disorders","placeboRate":"","totalAtRisk":32,"totalAffected":4,"trialsReporting":1},{"effect":"Injection site pain","drugRate":"1.9%","organSystem":"General disorders","placeboRate":"","totalAtRisk":159,"totalAffected":3,"trialsReporting":1},{"effect":"COLITIS ULCERATIVE","drugRate":"6.2%","organSystem":"Gastrointestinal disorders","placeboRate":"","totalAtRisk":32,"totalAffected":2,"trialsReporting":1},{"effect":"PYREXIA","drugRate":"6.2%","organSystem":"General disorders","placeboRate":"","totalAtRisk":32,"totalAffected":2,"trialsReporting":1},{"effect":"NASOPHARYNGITIS","drugRate":"6.2%","organSystem":"Infections and infestations","placeboRate":"","totalAtRisk":32,"totalAffected":2,"trialsReporting":1},{"effect":"PHARYNGITIS","drugRate":"6.2%","organSystem":"Infections and infestations","placeboRate":"","totalAtRisk":32,"totalAffected":2,"trialsReporting":1},{"effect":"ANAEMIA","drugRate":"3.1%","organSystem":"Blood and lymphatic system disorders","placeboRate":"","totalAtRisk":32,"totalAffected":1,"trialsReporting":1},{"effect":"ABDOMINAL PAIN UPPER","drugRate":"3.1%","organSystem":"Gastrointestinal disorders","placeboRate":"","totalAtRisk":32,"totalAffected":1,"trialsReporting":1},{"effect":"PERIPHERAL SWELLING","drugRate":"3.1%","organSystem":"General disorders","placeboRate":"","totalAtRisk":32,"totalAffected":1,"trialsReporting":1},{"effect":"ARTHRALGIA","drugRate":"3.1%","organSystem":"Musculoskeletal and connective tissue disorders","placeboRate":"","totalAtRisk":32,"totalAffected":1,"trialsReporting":1},{"effect":"OROPHARYNGEAL PAIN","drugRate":"3.1%","organSystem":"Respiratory, thoracic and mediastinal disorders","placeboRate":"","totalAtRisk":32,"totalAffected":1,"trialsReporting":1},{"effect":"NEUTROPENIA","drugRate":"0.0%","organSystem":"Blood and lymphatic system disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"THROMBOCYTOSIS","drugRate":"0.0%","organSystem":"Blood and lymphatic system disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"NONINFECTIVE CONJUNCTIVITIS","drugRate":"0.0%","organSystem":"Eye disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"ABDOMINAL PAIN","drugRate":"0.0%","organSystem":"Gastrointestinal disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"CONSTIPATION","drugRate":"0.0%","organSystem":"Gastrointestinal disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"DIARRHOEA","drugRate":"0.0%","organSystem":"Gastrointestinal disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"GASTROOESOPHAGEAL REFLUX DISEASE","drugRate":"0.0%","organSystem":"Gastrointestinal disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"NAUSEA","drugRate":"0.0%","organSystem":"Gastrointestinal disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"VOMITING","drugRate":"0.0%","organSystem":"Gastrointestinal disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"FATIGUE","drugRate":"0.0%","organSystem":"General disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"INFLAMMATION","drugRate":"0.0%","organSystem":"General disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"BRONCHITIS","drugRate":"0.0%","organSystem":"Infections and infestations","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"GASTROENTERITIS","drugRate":"0.0%","organSystem":"Infections and infestations","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"INFLUENZA","drugRate":"0.0%","organSystem":"Infections and infestations","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"RESPIRATORY TRACT INFECTION VIRAL","drugRate":"0.0%","organSystem":"Infections and infestations","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"STREPTOCOCCAL INFECTION","drugRate":"0.0%","organSystem":"Infections and infestations","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"TOOTH ABSCESS","drugRate":"0.0%","organSystem":"Infections and infestations","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"UPPER RESPIRATORY TRACT INFECTION","drugRate":"0.0%","organSystem":"Infections and infestations","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"VIRAL INFECTION","drugRate":"0.0%","organSystem":"Infections and infestations","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"VULVOVAGINAL MYCOTIC INFECTION","drugRate":"0.0%","organSystem":"Infections and infestations","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"JOINT INJURY","drugRate":"0.0%","organSystem":"Injury, poisoning and procedural complications","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"C-REACTIVE PROTEIN INCREASED","drugRate":"0.0%","organSystem":"Investigations","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"HEPATIC ENZYME INCREASED","drugRate":"0.0%","organSystem":"Investigations","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"MONOCYTE COUNT DECREASED","drugRate":"0.0%","organSystem":"Investigations","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"NEUTROPHIL COUNT DECREASED","drugRate":"0.0%","organSystem":"Investigations","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"WHITE BLOOD CELL COUNT DECREASED","drugRate":"0.0%","organSystem":"Investigations","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"MUSCULOSKELETAL PAIN","drugRate":"0.0%","organSystem":"Musculoskeletal and connective tissue disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"TREMOR","drugRate":"0.0%","organSystem":"Nervous system disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"GLYCOSURIA","drugRate":"0.0%","organSystem":"Renal and urinary disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"COUGH","drugRate":"0.0%","organSystem":"Respiratory, thoracic and mediastinal disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"EPISTAXIS","drugRate":"0.0%","organSystem":"Respiratory, thoracic and mediastinal disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"RHINITIS ALLERGIC","drugRate":"0.0%","organSystem":"Respiratory, thoracic and mediastinal disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"RHINORRHOEA","drugRate":"0.0%","organSystem":"Respiratory, thoracic and mediastinal disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"WHEEZING","drugRate":"0.0%","organSystem":"Respiratory, thoracic and mediastinal disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"DERMATITIS","drugRate":"0.0%","organSystem":"Skin and subcutaneous tissue disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"HANGNAIL","drugRate":"0.0%","organSystem":"Skin and subcutaneous tissue disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1},{"effect":"RASH","drugRate":"0.0%","organSystem":"Skin and subcutaneous tissue disorders","placeboRate":"","totalAtRisk":32,"totalAffected":0,"trialsReporting":1}],"specialPopulations":{"Pregnancy":"Available studies with use of adalimumab during pregnancy do not reliably establish an association between adalimumab and major birth defects. Clinical data are available from the Organization of Teratology Information Specialists (OTIS)/MotherToBaby Pregnancy Registry in pregnant women with rheumatoid arthritis (RA) or Crohns disease (CD) treated with adalimumab. Registry results showed rate of 10% for major birth defects with first trimester use of adalimumab in pregnant women with RA or CD and rate of 7.5% for major birth defects in the disease-matched comparison cohort. The lack of pattern of major birth defects is reassuring and differences between exposure groups may have impacted the occurrence of birth defects (see Data). Adalimumab is actively transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant (see Clinical Considerations). In an embryo-fetal perinatal development study conducted in cynomolgus monkeys, no fetal harm or malformations were observed with intravenous administration of adalimumab during organogenesis and later in gestation, at doses that produced exposures up to approximately 373 times the maximum recommended human dose (MRHD) of 40 mg subcutaneous without methotrexate (see Data). The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have background risk of major birth defects and miscarriage, which is unknown. Adalimumab is transferred across the placenta and may affect the infant's immune response.","Geriatric use":"A total of 519 RA patients 65 years of age and older, including 107 patients 75 years of age and older, received adalimumab in clinical studies RA-I through IV. No overall difference in effectiveness was observed between these patients and younger patients. The frequency of serious infection and malignancy among adalimumab treated patients 65 years of age and older was higher than for those less than 65 years of age. Consider the benefits and risks of AMJEVITA in patients 65 years of age and older.","Paediatric use":"The safety and effectiveness of AMJEVITA have been established for:reducing signs and symptoms of moderately to severely active polyarticular JIA in pediatric patients years of age and older.the treatment of moderately to severely active Crohns disease in pediatric patients years of age and older.Pediatric assessments for AMJEVITA demonstrate that AMJEVITA is safe and effective for pediatric patients in indications for which HUMIRA (adalimumab) is approved. However, AMJEVITA is"},"seriousAdverseEvents":[{"event":"ANAEMIA","detail":"Blood and lymphatic system disorders. 1 trial(s).","severity":"serious","incidence":"6.2%"},{"event":"COLITIS ULCERATIVE","detail":"Gastrointestinal disorders. 1 trial(s).","severity":"serious","incidence":"6.2%"},{"event":"PERICARDITIS","detail":"Cardiac disorders. 1 trial(s).","severity":"serious","incidence":"3.1%"},{"event":"HEADACHE","detail":"Nervous system disorders. 1 trial(s).","severity":"serious","incidence":"3.1%"},{"event":"LOSS OF CONSCIOUSNESS","detail":"Nervous system disorders. 1 trial(s).","severity":"serious","incidence":"3.1%"},{"event":"Abdominal abscess","detail":"Infections and infestations. 1 trial(s).","severity":"serious","incidence":"0.6%"},{"event":"Oral herpes","detail":"Infections and infestations. 1 trial(s).","severity":"serious","incidence":"0.6%"},{"event":"Upper respiratory tract infection","detail":"Infections and infestations. 1 trial(s).","severity":"serious","incidence":"0.6%"},{"event":"Congestive cardiomyopathy","detail":"Cardiac disorders. 1 trial(s).","severity":"serious","incidence":"0.6%"},{"event":"Psoriasis","detail":"Skin and subcutaneous tissue disorders. 1 trial(s).","severity":"serious","incidence":"0.6%"},{"event":"Furuncle","detail":"Infections and infestations. 1 trial(s).","severity":"serious","incidence":"0.0%"},{"event":"Kidney infection","detail":"Infections and infestations. 1 trial(s).","severity":"serious","incidence":"0.0%"},{"event":"Orchitis","detail":"Infections and infestations. 1 trial(s).","severity":"serious","incidence":"0.0%"},{"event":"Transient ischaemic attack","detail":"Nervous system disorders. 1 trial(s).","severity":"serious","incidence":"0.0%"},{"event":"Pericarditis","detail":"Cardiac disorders. 1 trial(s).","severity":"serious","incidence":"0.0%"},{"event":"Pancreatitis chronic","detail":"Gastrointestinal disorders. 1 trial(s).","severity":"serious","incidence":"0.0%"},{"event":"Hepatitis toxic","detail":"Hepatobiliary disorders. 1 trial(s).","severity":"serious","incidence":"0.0%"},{"event":"Exostosis","detail":"Musculoskeletal and connective tissue disorders. 1 trial(s).","severity":"serious","incidence":"0.0%"},{"event":"Foot deformity","detail":"Musculoskeletal and connective tissue disorders. 1 trial(s).","severity":"serious","incidence":"0.0%"},{"event":"Renal colic","detail":"Renal and urinary disorders. 1 trial(s).","severity":"serious","incidence":"0.0%"},{"event":"DYSPEPSIA","detail":"Gastrointestinal disorders. 1 trial(s).","severity":"serious","incidence":"0.0%"},{"event":"ENTERITIS","detail":"Gastrointestinal disorders. 1 trial(s).","severity":"serious","incidence":"0.0%"},{"event":"PANCREATITIS","detail":"Gastrointestinal disorders. 1 trial(s).","severity":"serious","incidence":"0.0%"},{"event":"ENTERITIS INFECTIOUS","detail":"Infections and infestations. 1 trial(s).","severity":"serious","incidence":"0.0%"},{"event":"GASTROENTERITIS","detail":"Infections and infestations. 1 trial(s).","severity":"serious","incidence":"0.0%"},{"event":"MENINGITIS ASEPTIC","detail":"Infections and infestations. 1 trial(s).","severity":"serious","incidence":"0.0%"},{"event":"PHARYNGITIS","detail":"Infections and infestations. 1 trial(s).","severity":"serious","incidence":"0.0%"},{"event":"URINARY TRACT INFECTION","detail":"Infections and infestations. 1 trial(s).","severity":"serious","incidence":"0.0%"},{"event":"HAND FRACTURE","detail":"Injury, poisoning and procedural complications. 1 trial(s).","severity":"serious","incidence":"0.0%"},{"event":"WRIST FRACTURE","detail":"Injury, poisoning and procedural complications. 1 trial(s).","severity":"serious","incidence":"0.0%"}]},"trials":[],"aliases":[],"company":"AbbVie","patents":[],"pricing":[],"_fixedAt":"2026-03-30T11:30:44.229612","_sources":{"trials":{"url":"https://clinicaltrials.gov/search?intr=ADALIMUMAB","method":"api_direct","source":"ClinicalTrials.gov","rawText":"","confidence":1,"sourceType":"ctgov","retrievedAt":"2026-04-19T23:42:04.302920+00:00"},"timeline":{"url":"https://en.wikipedia.org/wiki/Adalimumab","method":"deterministic","source":"Wikipedia","rawText":"","confidence":0.8,"sourceType":"wikipedia","retrievedAt":"2026-04-19T23:42:12.078634+00:00"},"mechanism":{"url":"","method":"ai_extraction","source":"FDA Label + Haiku","rawText":"","confidence":0.95,"sourceType":"fda_label","retrievedAt":"2026-04-20T12:48:22.673373+00:00"},"regulatory.ca":{"url":"","method":"api_direct","source":"Health Canada DPD","rawText":"","confidence":1,"sourceType":"health_canada_dpd","retrievedAt":"2026-04-19T23:42:10.687872+00:00"},"regulatory.eu":{"url":"","method":"api_direct","source":"European Medicines Agency","rawText":"","confidence":1,"sourceType":"ema_api","retrievedAt":"2026-04-19T23:42:04.327142+00:00"},"regulatory.us":{"url":"","method":"api_direct","source":"FDA Drugs@FDA","rawText":"","confidence":1,"sourceType":"fda_drugsfda","retrievedAt":"2026-04-19T23:42:01.338988+00:00"},"pharmacokinetics":{"url":"","method":"ai_extraction","source":"FDA Label + Haiku","rawText":"","confidence":0.95,"sourceType":"fda_label","retrievedAt":"2026-04-20T12:48:22.673394+00:00"},"publicationCount":{"url":"https://pubmed.ncbi.nlm.nih.gov/?term=ADALIMUMAB","method":"api_direct","source":"PubMed/NCBI","rawText":"","confidence":1,"sourceType":"pubmed","retrievedAt":"2026-04-19T23:42:11.523096+00:00"},"safety.boxedWarnings":{"url":"","method":"deterministic","source":"FDA Label (boxed_warning)","rawText":"WARNING: SERIOUS INFECTIONS and MALIGNANCY SERIOUS INFECTIONS Patients treated with adalimumab products including IDACIO are at increased risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions ( 5.1 )] . Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Discontinue IDACIO if a patient develops a serious infection or sepsis. Reported infections include: • Active t","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-19T23:41:58.758185+00:00"},"safety.safetySignals":{"url":"https://api.fda.gov/drug/event.json","method":"api_direct","source":"FDA FAERS","rawText":"","confidence":1,"sourceType":"fda_faers","retrievedAt":"2026-04-19T23:42:13.210094+00:00"},"mechanism.target_chembl":{"url":"","method":"api_direct","source":"ChEMBL mechanism: TNF-alpha inhibitor","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-19T23:42:12.078424+00:00"},"crossReferences.chemblId":{"url":"https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL1201580/","method":"api_direct","source":"ChEMBL (EMBL-EBI)","rawText":"","confidence":1,"sourceType":"chembl","retrievedAt":"2026-04-19T23:42:11.991716+00:00"},"safety.commonSideEffects":{"url":"","method":"deterministic","source":"ClinicalTrials.gov (2 trials)","rawText":"","confidence":1,"sourceType":"ctgov_results","retrievedAt":"2026-04-20T12:48:22.992714+00:00"},"regulatory.fda_application":{"url":"","method":"deterministic","source":"FDA Label","rawText":"BLA761255","confidence":1,"sourceType":"fda_label","retrievedAt":"2026-04-19T23:41:58.758240+00:00"}},"allNames":"d2e7, humira","offLabel":[],"synonyms":["yuflym","ADALIMUMAB-ADBM","adalimumab-atto","amjevita","adalimumab","humira","adalimumab (genetical recombination)","LU200134","D2E7"],"timeline":[{"date":"2002-12-31","type":"positive","source":"DrugCentral","milestone":"FDA approval (Abbvie Inc)"},{"date":"2003-09-08","type":"positive","source":"DrugCentral","milestone":"EMA approval (AbbVie Deutschland GmbH Co. KG)"},{"date":"2008-04-16","type":"positive","source":"DrugCentral","milestone":"PMDA approval (AbbVie GK)"}],"aiSummary":"IDACIO (adalimumab) is a TNF-alpha blocking monoclonal antibody indicated for nine inflammatory conditions including RA, JIA, PsA, AS, CD, UC, plaque psoriasis, hidradenitis suppurativa, and uveitis. The drug demonstrates linear pharmacokinetics with approximately 64% bioavailability, 2-week half-life, and 12 mL/hr clearance, with steady-state trough concentrations ranging from 5-12 mcg/mL depending on indication and concomitant MTX use. Serious risks include increased infection when combined with abatacept or anakinra, and live vaccines should be avoided. IDACIO represents a well-established TNF-blocking therapy with extensive clinical experience across multiple inflammatory indications.","brandName":"Humira","ecosystem":[],"mechanism":{"target":"Tumor Necrosis Factor-alpha (TNF-alpha)","novelty":"Follow-on","targets":[{"gene":"TNF","source":"DrugCentral","target":"Tumor necrosis factor","protein":"Tumor necrosis factor","isPrimary":true,"activityType":"","activityValue":null}],"moaClass":"Tumor Necrosis Factor Receptor Blocking Activity","modality":"Monoclonal antibody","drugClass":"TNF blocker","explanation":"Adalimumab products bind specifically to TNF-alpha and block its interaction with the p55 and p75 cell surface TNF receptors. Adalimumab products also lyse surface TNF expressing cells in vitro in the presence of complement. Adalimumab products do not bind or inactivate lymphotoxin (TNF-beta).\n\nTNF is a naturally occurring cytokine involved in normal inflammatory and immune responses. Elevated concentrations of TNF are found in the synovial fluid of patients with RA, JIA, PsA, and AS and play an important role in both the pathologic inflammation and the joint destruction that are hallmarks of these diseases. Increased concentrations of TNF are also found in psoriasis plaques.\n\nAdalimumab products modulate biological responses induced or regulated by TNF, including changes in the concentrations of adhesion molecules responsible for leukocyte migration (ELAM-1, VCAM-1, and ICAM-1 with an IC50 of 1-2 X 10-10 M).","oneSentence":"Adalimumab binds TNF-alpha and blocks interaction with p55 and p75 cell surface receptors.","technicalDetail":"Humira is a recombinant human immunoglobulin G1 monoclonal antibody that selectively binds to human tumor necrosis factor-alpha (TNF-alpha) with high affinity, inhibiting its interaction with cell surface TNF receptors and subsequent downstream signaling events that lead to inflammation.","_target_confidence":0.5},"_wikipedia":{"url":"https://en.wikipedia.org/wiki/Adalimumab","title":"Adalimumab","extract":"Adalimumab, sold under the brand name Humira and others, is a disease-modifying antirheumatic drug and monoclonal antibody used to treat rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa, and uveitis. It is administered by subcutaneous injection. It works by inactivating tumor necrosis factor (TNF).","wiki_history":"== History ==\nAdalimumab was the first fully human monoclonal antibody approved by the US Food and Drug Administration (FDA). It is derived from phage display.\n\nAdalimumab was discovered as a result of a collaboration between BASF Bioresearch Corporation and Cambridge Antibody Technology, U.K., itself a collaboration of the government-funded Medical Research Council and three academics, which began in 1993.\n\nInitially named D2E7, it was then further manufactured at BASF Bioresearch Corporation, developed by BASF Knoll (BASF Pharma), and ultimately manufactured and marketed by Abbott Laboratories after Abbott's acquisition of BASF Pharma. On 1 January 2013, Abbott split into two companies, one retaining the Abbott name and the other named AbbVie. As a result, AbbVie took over development and marketing of Humira. The brand name Humira stands for \"human monoclonal antibody in rheumatoid arthritis\", and was named by one of Abbott's employees, Richard J. Karwoski, who was also responsible for leading the effort to get Humira approved by the FDA.\n\nIt is the third TNF inhibitor, after infliximab and etanercept, to be approved in the United States. and etanercept is a TNF receptor-IgG fusion protein.\n\nThe drug candidate was discovered initially using CAT's phage display technology and named D2E7. The ultimate clinical candidate, D2E7, was created and manufactured at BASF Bioresearch Corporation and taken through most of the drug development process by BASF Knoll, then further development, manufacturing and marketing by Abbott Laboratories, after Abbott acquired the pharmaceutical arm of BASF Knoll.\n\nSince 2008, adalimumab had been approved by the FDA for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, moderate to severe chronic psoriasis and juvenile idiopathic arthritis. Although only approved for ulcerative colitis from late 2012, by the FDA in the disease's management, it had been used for several years in cases that h","wiki_society_and_culture":"== Society and culture ==\n\n===Economics ===\n\nThe UK NHS in 2019 listed Humira, Amgevita, Hulio, Hyrimoz, Idacio, and Imraldi as biosimilars available on (almost free) prescription, to be updated in February 2022. The annual cost of adalimumab, the costliest NHS drug, was expected to drop from £400m to £100m by 2021, the biggest saving in NHS history from a single drug negotiation.\n\nThe best-selling drugs list published by Genetic Engineering & Biotechnology News, shows that Humira occupied the  position for 2015 (billion}}) and 2016 (billion}}) From 2012 until the US patent expired in 2016, Humira led the list of top-selling pharmaceutical products, and in 2016, it had billion}} of global sales. Humira had the largest worldwide drug sales in 2019 and 2020 of US$19.7bn and US$20.4bn respectively.\n\n=== Biosimilars===\n\n\nFrom 2014, biosimilars were manufactured by several companies and sold at a lower price than before patent expiry.\n\nIn 2014, Indian drugmaker Cadila Healthcare declared the launch of the first adalimumab biosimilar at a fifth of its US price. The generic was launched under the brand name Exemptia.\n\nIn September 2016, the FDA approved Amgen's biosimilar adalimumab-atto, sold under the brand name Amjevita.\n\nIn August 2017, the FDA approved German pharmaceutical company Boehringer Ingelheim's biosimilar, Cyltezo.\n\nIn 2017, the biosimilars Amgevita, Solymbic, Imraldi, and Cyltezo were approved for use in the European Union.\n\nIn 2018, the biosimilars Halimatoz, Hefiya, Hyrimoz, and Hulio were approved for use in the European Union.\n\nFrom 2018, Adalimumab biosimilars became available in the European Union, allowing the National Health Service to make record-breaking cost-savings, as this is the single most expensive drug used in NHS hospitals, costing more than £400million a year for about 46,000 patients.\n\nIn October 2018, adalimumab-adaz (Hyrimoz) was approved for use in the United States.\n\nIn April 2019, Idacio and Kromeya were approved for use in the Euro"},"references":[{"id":1,"url":"https://drugcentral.org/drugcard/4904","fields":["approvals","synonyms","ATC","PK","indications","contraindications","DDIs","targets","patents","FAERS"],"source":"DrugCentral"},{"id":2,"url":"https://clinicaltrials.gov/search?intr=ADALIMUMAB","fields":["trials"],"source":"ClinicalTrials.gov"},{"id":3,"url":"https://pubmed.ncbi.nlm.nih.gov/?term=ADALIMUMAB","fields":["publications"],"source":"PubMed/NCBI"},{"id":4,"url":"https://en.wikipedia.org/wiki/Adalimumab","fields":["history","overview"],"source":"Wikipedia"}],"_emaChecked":true,"_enrichedAt":"2026-03-29T23:17:52.627845","_validation":{"fieldsValidated":7,"lastValidatedAt":"2026-04-20T12:48:24.072692+00:00","fieldsConflicting":0,"overallConfidence":0.95},"biosimilars":[{"form":"INJECTION","route":"SUBCUTANEOUS","company":"A-S Medication Solutions","brandName":"AMJEVITA","isOriginal":false,"marketingStatus":"BLA"},{"form":"INJECTION, SOLUTION","route":"SUBCUTANEOUS","company":"Sandoz Inc","brandName":"HYRIMOZ","isOriginal":false,"marketingStatus":"BLA"},{"form":"SOLUTION","route":"SUBCUTANEOUS","company":"Organon LLC","brandName":"Hadlima","isOriginal":false,"marketingStatus":"BLA"},{"form":"INJECTION, SOLUTION","route":"SUBCUTANEOUS","company":"Fresenius Kabi USA, LLC","brandName":"Idacio","isOriginal":false,"marketingStatus":"BLA"},{"form":"INJECTION, SOLUTION","route":"SUBCUTANEOUS","company":"Coherus BioSciences Inc","brandName":"YUSIMRY","isOriginal":false,"marketingStatus":"BLA"},{"form":"INJECTION","route":"SUBCUTANEOUS","company":"CELLTRION USA, Inc.","brandName":"Yuflyma","isOriginal":false,"marketingStatus":"BLA"}],"competitors":[{"drugName":"etanercept","drugSlug":"etanercept","fdaApproval":"1998-11-02","relationship":"same-class"},{"drugName":"infliximab","drugSlug":"infliximab","fdaApproval":"1998-08-24","relationship":"same-class"},{"drugName":"certolizumab pegol","drugSlug":"certolizumab-pegol","fdaApproval":"2008-04-22","relationship":"same-class"},{"drugName":"golimumab","drugSlug":"golimumab","fdaApproval":"2009-04-24","relationship":"same-class"}],"genericName":"adalimumab","indications":{"approved":[{"name":"Ankylosing spondylitis","source":"DrugCentral","snomedId":9631008,"regulator":"FDA","globalPrevalence":64000000,"prevalenceMethod":"ai-extracted","prevalenceSource":"Arthritis Care Res (Hoboken), 2016 (PMID:26713432)"},{"name":"Axial spondyloarthritis","source":"DrugCentral","snomedId":723116002,"regulator":"FDA"},{"name":"Behcet's disease","source":"DrugCentral","snomedId":310701003,"regulator":"FDA"},{"name":"Crohn's disease","source":"DrugCentral","snomedId":34000006,"regulator":"FDA","usPrevalence":780000,"globalPrevalence":5000000,"prevalenceMethod":"curated","prevalenceSource":"Lancet Gastroenterology, 2023"},{"name":"Hidradenitis suppurativa","source":"DrugCentral","snomedId":59393003,"regulator":"FDA","globalPrevalence":200000000,"prevalenceMethod":"ai-extracted","prevalenceSource":"Dermatology, 2025 (PMID:39715604)"},{"name":"Juvenile idiopathic arthritis","source":"DrugCentral","snomedId":410502007,"regulator":"FDA","prevalenceClass":"1-5 / 10 000","globalPrevalence":1640000,"prevalenceMethod":"orphanet","prevalenceSource":"Orphanet (24210707[PMID])"},{"name":"Non-infectious anterior uveitis","source":"DrugCentral","snomedId":267619000,"regulator":"FDA"},{"name":"Non-infectious intermediate, posterior and panuveitis","source":"DrugCentral","snomedId":733337008,"regulator":"FDA"},{"name":"Plaque psoriasis","source":"DrugCentral","snomedId":200965009,"regulator":"FDA","usPrevalence":7500000,"globalPrevalence":125000000,"prevalenceMethod":"curated","prevalenceSource":"WHO, 2023"},{"name":"Psoriasis with arthropathy","source":"DrugCentral","snomedId":33339001,"regulator":"FDA","usPrevalence":7500000,"globalPrevalence":125000000,"prevalenceMethod":"curated","prevalenceSource":"WHO, 2023"},{"name":"Psoriatic arthritis","source":"DrugCentral","snomedId":156370009,"regulator":"FDA","usPrevalence":null,"globalPrevalence":6000000,"prevalenceMethod":"curated","prevalenceSource":"Lancet Rheumatology, 2023"},{"name":"Pustular psoriasis","source":"DrugCentral","snomedId":200973000,"regulator":"FDA","usPrevalence":7500000,"globalPrevalence":125000000,"prevalenceMethod":"curated","prevalenceSource":"WHO, 2023"},{"name":"Pyoderma gangrenosum","source":"DrugCentral","snomedId":74578003,"regulator":"FDA"},{"name":"Rheumatoid arthritis","source":"DrugCentral","snomedId":69896004,"regulator":"FDA","usPrevalence":1500000,"globalPrevalence":18000000,"prevalenceMethod":"curated","prevalenceSource":"Lancet Rheumatology, 2023"},{"name":"Ulcerative colitis","source":"DrugCentral","snomedId":64766004,"regulator":"FDA","usPrevalence":900000,"globalPrevalence":5000000,"prevalenceMethod":"curated","prevalenceSource":"Lancet Gastroenterology, 2023"}],"offLabel":[],"pipeline":[]},"_fixedFields":["primaryTarget"],"drugCategory":"active","labelChanges":[],"relatedDrugs":[{"drugId":"etanercept","brandName":"etanercept","genericName":"etanercept","approvalYear":"1998","relationship":"same-class"},{"drugId":"infliximab","brandName":"infliximab","genericName":"infliximab","approvalYear":"1998","relationship":"same-class"},{"drugId":"certolizumab-pegol","brandName":"certolizumab pegol","genericName":"certolizumab pegol","approvalYear":"2008","relationship":"same-class"},{"drugId":"golimumab","brandName":"golimumab","genericName":"golimumab","approvalYear":"2009","relationship":"same-class"}],"trialDetails":[{"nctId":"NCT07495644","phase":"","title":"Efficacy of Different Biological Treatments in Patients With Inflammatory Bowel Disease After One Year of Treatment in Upper Egypt","status":"NOT_YET_RECRUITING","sponsor":"Assiut University","startDate":"2026-03-01","conditions":["Inflamatory Bowel Disease (Crohn&#39;s and Ulcerative Colitis)"],"enrollment":95,"completionDate":"2027-06"},{"nctId":"NCT06926478","phase":"PHASE1","title":"Subconjunctival Humira for Boston Keratoprosthesis","status":"NOT_YET_RECRUITING","sponsor":"Massachusetts Eye and Ear Infirmary","startDate":"2026-06-01","conditions":["Penetrating Keratoplasty","Multiple Graft Failure","Ocular Cicatricial Pemphigoid","Stevens-Johnson Syndrome"],"enrollment":8,"completionDate":"2028-06-01"},{"nctId":"NCT07491913","phase":"NA","title":"Biologic Treatment Withdrawal in Takayasu Arteritis Patients in Sustained Remission","status":"RECRUITING","sponsor":"Marmara University","startDate":"2025-06-15","conditions":["Takayasu Arteritis"],"enrollment":40,"completionDate":"2027-12-15"},{"nctId":"NCT07348588","phase":"PHASE1,PHASE2","title":"Intravitreal Adalimumab in Inherited and Degenerative Retinal Diseases","status":"ACTIVE_NOT_RECRUITING","sponsor":"Centro de Pesquisa Rubens Siqueira","startDate":"2024-03-01","conditions":["Retinitis Pigmentosa (RP)","Extensive Macular Atrophy With Pseudodrusen (EMAP)"],"enrollment":30,"completionDate":"2026-12-01"},{"nctId":"NCT06654882","phase":"PHASE3","title":"Trial of Sequential Medications AfteR TNFi Failure in Juvenile Idiopathic Arthritis","status":"RECRUITING","sponsor":"Duke University","startDate":"2026-01-09","conditions":["Polyarticular Course Juvenile Idiopathic Arthritis (JIA)"],"enrollment":400,"completionDate":"2026-12"},{"nctId":"NCT02840175","phase":"PHASE3","title":"Treatment Tapering in JIA With Inactive Disease","status":"COMPLETED","sponsor":"Assistance Publique - Hôpitaux de Paris","startDate":"2017-05-18","conditions":["Juvenile Idiopathic Arthritis"],"enrollment":62,"completionDate":"2020-10-01"},{"nctId":"NCT07486843","phase":"PHASE4","title":"Preventing Structural Damage in Early Psoriatic Arthritis","status":"RECRUITING","sponsor":"Chinese University of Hong Kong","startDate":"2026-03-16","conditions":["Psoriatic Arthritis (PsA)"],"enrollment":108,"completionDate":"2028-12-31"},{"nctId":"NCT04527380","phase":"PHASE3","title":"A Study of Ixekizumab (LY2439821) in Children With Juvenile Idiopathic Arthritis Categories of Enthesitis-related Arthritis (Including Juvenile Onset Ankylosing Spondylitis) and Juvenile Psoriatic Arthritis","status":"ACTIVE_NOT_RECRUITING","sponsor":"Eli Lilly and Company","startDate":"2021-04-13","conditions":["Juvenile Psoriatic Arthritis","Enthesitis Related Arthritis"],"enrollment":101,"completionDate":"2028-04"},{"nctId":"NCT06045754","phase":"PHASE4","title":"A Study of Vedolizumab Intravenous (IV) and Adalimumab or Vedolizumab and Ustekinumab in Adults With Crohn's Disease","status":"RECRUITING","sponsor":"Takeda","startDate":"2024-04-18","conditions":["Crohn's 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Adalimumab or Verapamil in New Onset Type 1 Diabetes","status":"RECRUITING","sponsor":"City of Hope Medical Center","startDate":"2026-03-30","conditions":["Type 1 Diabetes","New Onset"],"enrollment":120,"completionDate":"2031-04-15"},{"nctId":"NCT05803187","phase":"","title":"Clinical Study of Stage IV Psoriasis in Children With Geleli","status":"COMPLETED","sponsor":"Bio-Thera Solutions","startDate":"2023-04-05","conditions":["Plaque Psoriasis"],"enrollment":80,"completionDate":"2025-03-30"},{"nctId":"NCT04372108","phase":"","title":"A Study to Assess the Long-Term Safety of Ustekinumab Versus Other Biologics in Patients With Crohn's Disease and Ulcerative Colitis","status":"RECRUITING","sponsor":"Janssen Scientific Affairs, LLC","startDate":"2021-06-24","conditions":["Crohn Disease","Colitis, Ulcerative"],"enrollment":1056,"completionDate":"2030-08-30"},{"nctId":"NCT00508547","phase":"","title":"Psoriasis Longitudinal Assessment and 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