Natalizumab and the role of alpha 4-integrin antagonism in the treatment of multiple sclerosis.

Natalizumab is a powerful new therapy with a novel mechanism of action for the treatment of multiple sclerosis. In a randomized, double-blind, Phase III study (the AFFIRM [Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis] study), natalizumab monotherapy 300 mg intravenous every 4 weeks reduced the risk of sustained disability progression by 42% and annualized relapse rate by 68% over 2 years (both p < 0.001 versus placebo). Natalizumab was approved in the US in November 2004 for the treatment of relapsing multiple sclerosis, but was voluntarily withdrawn in February 2005 due to three cases of progressive multifocal leukoencephalopathy. Following a safety evaluation and regulatory review, the US FDA approved natalizumab as monotherapy for the treatment of relapsing multiple sclerosis in June 2006 generally for patients who have had an inadequate response to, or are unable to tolerate, alternative treatments.