Natalizumab reduced the rate of clinical relapse at one year by 68% and the risk of sustained progression of disability by 42—54% over 2 years in its pivotal phase III trial (AFFIRM) in relapsing—remitting multiple sclerosis (RRMS). Natalizumab is generally well tolerated, but due to rare and potentially fatal side-effects, it was approved with a restricted-distribution format in 2006. Expert statements and the European Medical Agency recommend the use of natalizumab after failure of first-line disease-modifying therapies in patients with relapsing forms of MS. As part of the risk management plan, worldwide extensive safety programmes aim to provide more data on natalizumab safety in clinical practice. At the end of September 2008, 48 000 patients have received natalizumab and 18 000 patients are on treatment for at least 1 year. The assessment of risk and benefit is still ongoing.
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