Abstract
Natalizumab, a new disease-modifying therapy for relapsing remitting multiple sclerosis (RRMS), is a humanized monoclonal antibody which binds to alpha(4)beta(1)-integrin. In a Phase 3 trial, 2 years of natalizumab monotherapy reduced the mean annualized relapse rate (ARR) by 68% compared with placebo (p < 0.001) and the risk of sustained disability progression was reduced by 42% in the natalizumab group (hazard ratio [HR] 0.58; 95% confidence interval [CI] 0.43-0.77; p < 0.001). Natalizumab decreased the mean number of new or enlarging T2-hyperintense lesions by 83% over 2 years and the mean number of Gd+ lesions by 92% at 2 years (both p < 0.001). In another Phase 3 trial, natalizumab with interferon (IFN) beta-1a reduced the mean ARR by 55% at 2 years compared with IFNbeta-1a alone (p < 0.001) and risk of sustained disability progression was reduced by 24% (HR 0.76; 95% CI 0.61-0.96; p = 0.02). Six percent of patients developed persistent antinatalizumab antibodies with loss of efficacy. The risk of developing progressive multifocal leukoencephalopathy (PML) is been estimated at 1:1000 over 18 months; the longer term risk for PML is uncertain. The benefits and risks of natalizumab support its use as monotherapy for RRMS with high disease activity despite treatment with IFNbeta, and for patients with rapidly evolving severe RRMS.