Drug Identification Number (DIN): 02286386
Tysabri is a type of protein called a monoclonal antibody that is produced from mammalian cells using recombinant DNA techniques (a series of procedures used to join together DNA segments). Tysabri is the first in a class of agents called selective adhesion molecule inhibitors.
Indications and use
Tysabri is indicated as a monotherapy for people with relapsing-remitting MS to reduce the frequency of relapses, delay the progression of disability and reduce the number and volume of brain lesions seen on magnetic resonance imaging (MRI). It is generally recommended for people with MS who have not responded adequately to other disease-modifying therapies or who are unable to tolerate them.
Tysabri is not approved for people with CIS or progressive MS. For information on CIS approved treatment options and treatments for progressive MS, please speak with your physician or contact the MS Society of Canada at 1-800-268-7582.
Administration and dose
Tysabri is administered as an intravenous (into the vein) injection over time (an infusion) in a specialized infusion centre by a health professional. The recommended dose of Tysabri is 300 mg every 4 weeks.
Mechanism of action (MOA)
In MS, inflammatory T cells enter the central nervous system by attaching to the blood-brain barrier with “sticky molecules”, called alpha-4 integrins. Tysabri blocks alpha-4 integrin and prevents T cells from entering the central nervous system, where they cause inflammation and damage to myelin.
Common side effects include: urinary (bladder) infection, sore throat and runny or blocked up nose, shivering, itchy rash (hives), headache, dizziness, nausea, vomiting, joint pain, fever and tiredness. Less common side effects include anemia, cough, muscle cramps and depression.
Treatment with Tysabri (natalizumab) has been associated with an increased risk of progressive multifocal leukoencephalopathy (PML). PML can cause disability or death. Healthcare professionals must monitor people on Tysabri for any new sign or symptom that may be suggestive of PML. Tysabri should be withheld immediately at the first sign or symptom suggestive of PML.
Risk of PML
Three factors that are known to increase the risk of PML in people treated with Tysabri: the presence of anti-JCV antibodies, longer treatment duration (especially beyond 24 months) and prior treatment with an immunosuppressant, which appears independent of Tysabri treatment duration. People who have all three risk factors have the highest risk of PML. The risks and benefits of continuing Tysabri therapy should be carefully considered in these people.
This is not a comprehensive list of all possible side effects of Tysabri. Please see the Tysabri product monograph for a list of other potentially serious side effects. It is important that those with MS discuss side effects about any medication they are considering with their physician. (*Health Canada, product monograph for Tysabri.)
Some people taking Tysabri develop “neutralizing” antibodies (NAb). Persistent NAbs to Tysabri are associated with a lesser treatment effect and an increased risk of hypersensitivity reactions and/or infusion-related reactions (rigors, nausea/vomiting and flushing). Antibody testing should be performed if NAbs are suspected. The occurrence of NAbs may be transient. If they persist, discontinuation of treatment should be considered.
Clinical Trials in Relapsing-Remitting MS
AFFIRM Study: Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis
This clinical trial involved 942 people with relapsing-remitting MS who were treated with either Tysabri or placebo (a treatment that has no active medication) for over 3 years. Results of the study showed that Tysabri reduced the risk of sustained progression of disability compared to placebo. Tysabri reduced the annual relapse rate by 68% compared to placebo and also reduced the number of brain lesions on MRI.1 [Polman et al. N Engl J Med 2006; 354: 899-910]
SENTINEL Study: Safety and Efficacy of Natalizumab in Combination with Interferon Beta-1a in Patients with Relapsing Remitting Multiple Sclerosis
This study examined whether the combination of Tysabri and Avonex was safe and more effective than Avonex alone in people who were continuing to have relapses while on Avonex monotherapy. A total of 1,171 people taking Avonex for relapsing-remitting MS were treated with Tysabri or a placebo infusion for up to 120 weeks. The study was stopped one month early after two cases of PML had been reported. At 1 and 2 years, the annual relapse rate was reduced about 54% with the Tysabri/Avonex combination compared to Avonex alone. Combination therapy also reduced the probability of disease progression at 2 years, and reduced the number of brain lesions seen on MRI compared to Avonex alone.2 [Rudick et al. N Engl J Med 2006; 354: 911-923]
Tysabri costs approximately $40,000 per year. Private and group health plans may provide some coverage for people who meet the prescribing criteria. Financial assistance through the Biogen ONETM program at 1-855-MSONE-00 or 1-855-676-6300. Assistance with treatment costs varies among provinces and private insurance companies. For more information on reimbursement, please contact the MS Society at 1-800-268-7582.
Drug support program
Further information for persons with MS is available from Biogen ONETM program at 1-855-MSONE-00 or 1-855-676-6300.
Polman CH, O’Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354: 899-910. Rudick RA, Stuart WH, Calabresi PA, et al. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 2006; 354: 911-923.
Tysabri® is a registered trademark of Biogen Canada Inc. and Elan Pharmaceuticals