Multiple Sclerosis Journal

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.

Natalizumab therapy for patients with multiple sclerosis (MS) has been associated with both improved clinical outcomes and an increased incidence of progressive multifocal leukoencephalopathy (PML). We provide details of the etiology and recent history of PML as associated with immunosuppressive disease states, including MS. Furthermore, it offers clinical guidance on differentiating PML from a MS relapse and a review of the current treatment options for patients suspected of having developed the complication.

Natalizumab, a humanized monoclonal antibody directed against α4-integrin is a first-in-class disease-modifying therapy for the treatment of relapsing multiple sclerosis. Natalizumab is highly effective but has been associated with a risk of progressive multifocal leukoencephalopathy. Since the efficacy of natalizumab in relapsing forms of multiple sclerosis is viewed as superior to first-line agents, a growing number of neurologists are using natalizumab as the treatment of choice for patients with worsening MS. Owing to the recently reported cases of progressive multifocal leukoencephalopathy, a panel of neurologists met in February 2009 to discuss best practices for the use of natalizumab, with the goal of developing consensus-based recommendations on patient management to minimize the risk of progressive multifocal leukoencephalopathy. The panel consisted of a cross section of academic and community neurologists from the United States who treat multiple sclerosis in large centers and have extensive experience with natalizumab (approximating 2000 patient-years combined experience). This paper summarizes the panel's recommendations on the following: (1) appropriate patient selection for natalizumab; (2) routine monitoring and management of adverse events during natalizumab therapy; and (3) clinical vigilance monitoring and risk reduction for progressive multifocal leukoencephalopathy.