B-Cell Depletion with Rituximab in Relapsing–Remitting Multiple Sclerosis
ABSTRACT
Background
There is increasing evidence that B lymphocytes areinvolved in the pathogenesis of multiple sclerosis, and theymay be a therapeutic target. Rituximab, a monoclonal antibody,selectively targets and depletes CD20+ B lymphocytes.
Methods
In a phase II, double-blind, 48-week trial involving104 patients with relapsing–remitting multiple sclerosis,we assigned
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69 |
patients to receive 1000 mg of intravenous rituximaband |
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35 |
patients to receive placebo |
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on days 1 and 15. |
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The primaryend point was the total count of gadolinium-enhancing lesionsdetected on magnetic resonance imaging scans of the brain atweeks 12, 16, 20, and 24. Clinical outcomes included safety,the proportion of patients who had relapses, and the annualizedrate of relapse.
Results
As compared with patients who received placebo, patientswho received rituximab had reduced counts of total gadolinium-enhancinglesions at weeks 12, 16, 20, and 24 (P<0.001) and of totalnew gadolinium-enhancing lesions over the same period (P<0.001);these results were sustained for 48 weeks (P<0.001). As comparedwith patients in the placebo group, the proportion of patientsin the rituximab group with relapses was significantly reducedat week 24 (14.5% vs. 34.3%, P=0.02) and week 48 (20.3% vs. 40.0%, P=0.04).
More patients in the rituximab group than inthe placebo group had adverse events within 24 hours after thefirst infusion, most of which were mild-to-moderate events;after the second infusion, the numbers of events were similarin the two groups.
Conclusions
A single course of rituximab reduced inflammatorybrain lesions and clinical relapses for 48 weeks. This trialwas not designed to assess long-term safety or to detect uncommonadverse events. The data provide evidence of B-cell involvementin the pathophysiology of relapsing–remitting multiplesclerosis.
Source Information
From the Department of Neurology,
University of California at San Francisco,
San Francisco (S.L.H., E.W.);
Montreal Neurological Institute,
McGill University (D.L.A., J.A., A.B.-O.), and
NeuroRx Research (D.L.A.) —
both in Montreal;
Barrow Neurology Clinics,
Phoenix, AZ (T.V.);
Mellen Center for Multiple Sclerosis,
Cleveland Clinic, Cleveland (R.J.F.);
Biogen Idec,
Cambridge, MA (M.P.); and
Genentech, South San Francisco, CA (N.S., S.A., A.L.-G., C.H.S.).