Last reviewed 2026-04-20 · How we verify

Enbrel (etanercept)

Enbrel works by binding to tumor necrosis factor, a protein that promotes inflammation, thereby reducing inflammation and alleviating symptoms.

Enbrel (etanercept) is a tumor necrosis factor blocker, a type of biologic medication. It was originally developed by Immunex and is used to treat various inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, and plaque psoriasis. Enbrel works by binding to tumor necrosis factor, a protein that promotes inflammation, thereby reducing inflammation and alleviating symptoms. It is a patented medication with a long history of FDA approval since 1998. Key safety considerations include an increased risk of infections and the potential for allergic reactions.

At a glance

Mechanism of action

TNF is naturally occurring cytokine that is involved in normal inflammatory and immune responses. It plays an important role in the inflammatory processes of RA, polyarticular JIA, PsA, and AS and the resulting joint pathology. In addition, TNF plays role in the inflammatory process of PsO. Elevated levels of TNF are found in involved tissues and fluids of patients with RA, JIA, PsA, AS, and PsO.Two distinct receptors for TNF (TNFRs), 55 kilodalton protein (p55) and 75 kilodalton protein (p75), exist naturally as monomeric molecules on cell surfaces and in soluble forms. Biological activity of TNF is dependent upon binding to either cell surface TNFR.Etanercept products are dimeric soluble forms of the p75 TNF receptor that can bind TNF molecules. Etanercept products inhibit binding of TNF- and TNF- (lymphotoxin alpha [LT-]) to cell surface TNFRs, rendering TNF biologically inactive. In in vitro studies, large complexes of etanercept with TNF- were not detecte

Approved indications

• Ankylosing spondylitis
• Juvenile idiopathic arthritis
• Nonradiographic axial spondyloarthritis
• Plaque psoriasis
• Psoriasis with arthropathy
• Rheumatoid arthritis

Boxed warnings

• WARNING: SERIOUS INFECTIONS and MALIGNANCIES WARNING: SERIOUS INFECTIONS and MALIGNANCIES See full prescribing information for complete boxed warning. SERIOUS INFECTIONS 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. ( 5.1 ) Enbrel should be discontinued if a patient develops a serious infection or sepsis during treatment. ( 5.1 ) Perform test for latent TB; if positive, start treatment for TB prior to starting Enbrel. ( 5.1 ) Monitor all patients for active TB during treatment, even if initial latent TB test is negative. ( 5.1 ) MALIGNANCIES Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF-blockers, including Enbrel. ( 5.3 ) SERIOUS INFECTIONS Patients treated with Enbrel are at increased risk for developing serious infections that may lead to hospitalization or death [see Warnings and Precautions (5.1) and Adverse Reactions (6) ] . Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Enbrel should be discontinued if a patient develops a serious infection or sepsis. Reported infections include: Active tuberculosis, including reactivation of latent tuberculosis. Patients with tuberculosis have frequently presented with disseminated or extrapulmonary disease. Test patients for latent tuberculosis before Enbrel use and during therapy. Initiate treatment for latent infection prior to Enbrel 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. The risks and benefits of treatment with Enbrel should be carefully considered 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 Enbrel, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. MALIGNANCIES Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF-blockers, including Enbrel.

Common side effects

• Infections
• Injection site reactions
• Pneumonia
• Cellulitis
• Septic arthritis
• Bronchitis
• Gastroenteritis
• Pyelonephritis
• Sepsis
• Abscess
• Osteomyelitis
• Tuberculosis

Key clinical trials

• Trial of Sequential Medications AfteR TNFi Failure in Juvenile Idiopathic Arthritis (PHASE3)
• A Study of Tildrakizumab in Pediatric Subjects With Chronic Plaque Psoriasis (PHASE2,PHASE3)
• Treatment Tapering in JIA With Inactive Disease (PHASE3)
• Combination of Baricitinib and Anti-TNF in Rheumatoid Arthritis (PHASE3)
• Psoriasis Longitudinal Assessment and Registry
• A Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Subcutaneously Administered Guselkumab for the Treatment of Chronic Plaque Psoriasis in Pediatric Participants (PHASE3)
• TNF-α Treatment of Blast-Induced Tinnitus (PHASE2)
• Application of the Personalized N-of-1 Trial Design in Patients With Rheumatoid Arthritis

Primary sources

Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.

Competitive intelligence

For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:

• Enbrel CI brief — competitive landscape report
• Enbrel updates RSS · CI watch RSS
• Immunex portfolio CI