Clinical efficacy and benefit of natalizumab

Natalizumab is the first α4-integrin antagonist indicated for the treatment of relapsing multiple sclerosis (MS). Natalizumab has been shown to delay the accumulation of physical disability and reduce relapses. In two large, double-blind, randomized, placebo-controlled, phase 3 clinical trials, natalizumab was effective as a monotherapy as compared with placebo, and in combination with interferon β as compared with placebo and interferon β. Natalizumab in combination with glatiramer acetate was also effective in a phase 2 clinical trial when compared with placebo and glatiramer acetate. Natalizumab monotherapy achieved a 68% relative reduction in annualized relapse rate, and 42% and 54% reductions in disability progression sustained for 12 and 24 weeks, respectively. In a subset of patients with highly active disease, natalizumab proved more effective, decreasing relapse rates by 81% and progression of disability (sustained for 24 weeks) by 64%. Natalizumab-treated patients experienced significant improvements in quality of life, as measured by the Short Form-36, as well as a 35% reduction in risk of clinically significant vision loss. Recent analyses also have demonstrated the potential for natalizumab to induce a state of ‘no disease activity’ and actual improvement in physical disability. The purpose of this paper is to review evidence for the efficacy of natalizumab, and put its use in MS into perspective.