Last reviewed 2026-04-20 · How we verify

Tysabri (NATALIZUMAB)

Natalizumab blocks α4 integrins on leukocytes, preventing their adhesion to VCAM-1 and MAdCAM-1, reducing inflammation in MS and Crohn's disease.

Natalizumab (Tysabri), marketed by Biogen Idec, is a leading therapeutic for multiple sclerosis with a key composition patent expiring in 2028. Its mechanism of blocking α4 integrins on leukocytes effectively reduces inflammation, providing a significant clinical benefit over other same-class drugs such as muromonab-CD3 and mycophenolic acid. The primary risk is the potential increase in competition post-patent expiry, particularly from off-patent alternatives like leflunomide, which is already available as a generic.

At a glance

Mechanism of action

Natalizumab works by binding to α4 integrins on leukocytes, which prevents these cells from sticking to and crossing the blood vessels into inflamed tissues. This reduces the recruitment of immune cells and subsequent inflammation in conditions like multiple sclerosis and Crohn's disease.

Approved indications

• Multiple Sclerosis
• Crohn's Disease

Boxed warnings

• WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY TYSABRI increases the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability. Risk factors for the development of PML include the presence of anti-JCV antibodies, duration of therapy, and prior use of immunosuppressants. These factors should be considered in the context of expected benefit when initiating and continuing treatment with TYSABRI [ see Warnings and Precautions ( 5.1 ) ]. Healthcare professionals should monitor patients on TYSABRI for any new sign or symptom that may be suggestive of PML. TYSABRI dosing should be withheld immediately at the first sign or symptom suggestive of PML. For diagnosis, an evaluation that includes a gadolinium-enhanced magnetic resonance imaging (MRI) scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA are recommended [ see Contraindications ( 4 ), Warnings and Precautions ( 5.1 ) ]. Because of the risk of PML, TYSABRI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the TOUCH ® Prescribing Program [ see Warnings and Precautions ( 5.2 ) ]. WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY See full prescribing information for complete boxed warning TYSABRI increases the risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability ( 5.1 ) Risk factors for the development of PML include the presence of anti-JCV antibodies, duration of therapy, and prior use of immunosuppressants. These factors should be considered in the context of expected benefit when initiating and continuing treatment with TYSABRI ( 5.1 ) Monitor patients, and withhold TYSABRI immediately at the first sign or symptom suggestive of PML ( 4 , 5.1 ) Because of the risk of PML, TYSABRI is available only through a restricted distribution program called the TOUCH ® Prescribing Program ( 5.1 , 5.2 )

Common side effects

• Headache
• Fatigue
• Arthralgia
• Chest discomfort
• Other hypersensitivity reactions
• Acute hypersensitivity reactions
• Seasonal allergy
• Rigors
• Weight increased
• Weight decreased
• Urinary tract infection
• Lower respiratory tract infection

Drug interactions

• immunosuppressants (e.g., 6-mercaptopurine, azathioprine, cyclosporine, or methotrexate)
• inhibitors of TNF-α
• corticosteroids
• chronic immunosuppressant or immunomodulatory therapy

Key clinical trials

• Evaluation of Early Changes Visible to the Diffusion MRI in Response to Two Years of Treatment With Tysabri in Patients With Multiple Sclerosis (PHASE4)
• Study of the Mechanisms of Action of Cladribine in Multiple Sclerosis (NA)
• Natalizumab for the Treatment of People With Inflammatory Demyelination Suggestive of Multiple Sclerosis, or Definite Multiple Sclerosis, at First Presentation (AttackMS) (PHASE2)
• Best Available Therapy Versus Autologous Hematopoietic Stem Cell Transplant for Multiple Sclerosis (BEAT-MS) (PHASE3)
• Implication of 5-HT7 Receptor in Inflammatory Mechanisms in Multiple Sclerosis
• Cladribine Tablets After Treatment With Natalizumab (CLADRINA) (PHASE4)
• A Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of Natalizumab (BG00002) Administered Subcutaneously to Japanese Participants With Relapsing-Remitting Multiple Sclerosis (PHASE3)
• A Study to Learn More About The Safety of Diroximel Fumarate (VUMERITY®) in Participants Who Took it During Pregnancy And About the Health of Their Babies

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:

• Tysabri CI brief — competitive landscape report
• Tysabri updates RSS · CI watch RSS
• Biogen Idec portfolio CI