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B-Cell Depletion for MS

Rituximab showed promising results in a preliminary trial.

Rituximab is a genetically engineered chimeric monoclonal antibody that depletes CD20-positive B cells. These researchers conducted a 48-week, phase 2, multicenter, placebo-controlled, manufacturer-funded trial of rituximab for relapsing remitting multiple sclerosis (MS). They randomized 104 patients 2:1 to receive rituximab or placebo, administered intravenously on days 1 and 15. The primary endpoint was the total number of gadolinium-enhanced lesions recorded on T1-weighted MRI at weeks 12, 16, 20, and 24.

Compared with placebo recipients, rituximab recipients had a 91% reduction in the primary endpoint, and the reduction was sustained at 48 weeks. At week 24, the proportion of patients with clinically confirmed relapses was significantly lower in the rituximab group than in the placebo group (14.5% vs. 34.3%). Adverse events with rituximab included infusion-associated reactions that were generally mild-to-moderate. Four patients had more-severe, grade-3 infusion-associated events, including headache, back pain, depression, pain, pruritus, and rash. Serious adverse events occurred in 14% of the placebo group and in 13% of the rituximab group. The rates of infection were similar in the two groups, and no opportunistic infections were reported.

Comment: If these encouraging results are confirmed in a phase III trial, they will establish B cells as a novel cellular target for MS therapy. As the authors note, issues of long-term safety of rituximab must still be addressed, given reports to the FDA of progressive multifocal leukoencephalopathy in patients with lupus who were treated with rituximab.

— Samia J. Khoury, MD

Dr. Khoury is Professor of Neurology, Harvard Medical School, and Co-Director of the Partners MS Center, Brigham and Women’s Hospital, Boston.

Published in Journal Watch Neurology February 13, 2008

Citation(s):

Hauser SL et al. B-cell depletion with rituximab in relapsing–remitting multiple sclerosis. N Engl J Med 2008 Feb 14; 358:676.

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