A randomized, placebo-controlled trial of natalizumab for relapsing XXXX .

@entity1 @entity1295 @entity56 @entity2287 @entity15
BACKGROUND: Natalizumab is the first alpha4 integrin antagonist in a new class of selective adhesion-molecule inhibitors. We report the results of a two-year phase 3 trial of natalizumab in @entity1 with relapsing @entity15 . METHODS: Of a total of 942 @entity1 , 627 were randomly assigned to receive natalizumab (at a dose of 300 mg) and 315 to receive placebo by intravenous infusion every four weeks for more than two years. The primary end points were the rate of clinical relapse at one year and the rate of sustained progression of disability, as measured by the Expanded Disability Status Scale, at two years. RESULTS: Natalizumab reduced the risk of sustained progression of disability by 42 percent over two years (hazard ratio, 0.58; 95 percent confidence interval, 0.43 to 0.77; P<0.001). The cumulative probability of progression (on the basis of Kaplan-Meier analysis) was 17 percent in the natalizumab group and 29 percent in the placebo group. Natalizumab reduced the rate of clinical relapse at one year by 68 percent (P<0.001) and led to an 83 percent reduction in the accumulation of new or enlarging hyperintense lesions, as detected by T2-weighted magnetic resonance imaging (MRI), over two years (mean numbers of lesions, 1.9 with natalizumab and 11.0 with placebo; P<0.001). There were 92 percent fewer lesions (as detected by @entity2287 -enhanced MRI) in the natalizumab group than in the placebo group at both one and two years (P<0.001). The adverse events that were significantly more frequent in the natalizumab group than in the placebo group were @entity1295 (27 percent vs. 21 percent, P=0.048) and @entity56 (9 percent vs. 4 percent, P=0.012). @entity56 reactions of any kind occurred in 25 @entity1 receiving natalizumab (4 percent), and serious @entity56 occurred in 8 @entity1 (1 percent). CONCLUSIONS: Natalizumab reduced the risk of the sustained progression of disability and the rate of clinical relapse in @entity1 with relapsing @entity15 . Adhesion-molecule inhibitors hold promise as an effective treatment for relapsing @entity15 . (ClinicalTrials.gov number, NCT00027300.).
