Rituximab offers hope for new treatment approach for MS
Using rituximab to deplete B-cells reduces the number of inflammatory brain lesions and clinical relapses in patients with multiple sclerosis, a phase II trial has shown.
Researchers compared the effects of the drug with those of placebo in 104 patients with relapsing-remitting MS. Patients who received 1g rituximab on days 1 and 15 of the 48-week study had an average of 0.5 gadolinium-enhancing lesions at weeks 12, 16, 20 and 24 compared with 5.5 lesions in patients given placebo, a relative reduction of 91 per cent. Fewer patients treated with rituximab had relapsed by week 48 (20.3 per cent vs 40.0 per cent in the placebo group; P=0.04).
The reduction in inflammatory lesions occurred within four weeks of the first dose. This, say the researchers, suggests that rituximab’s beneficial effects are unlikely to be due to a reduction in pathogenic antibodies. “A more likely explanation is that the effects of rituximab . . . resulted from lysis of memory B cells located in the peripheral blood and lymphoid tissues, or perhaps the central nervous system.” The researchers add that interference with antigen presentation by B cells or with activation of T cells or macrophages by pro-inflammatory B-cell cytokines may also play a role (New England Journal of Medicine 2008;358:676). The trial was sponsored by Genentech and Biogen Idec.
The author of an accompanying commentary (ibid, p664) describes the findings as remarkable, but warns: “Just as manipulation of a complicated immune response may provide treatment opportunities and improved understanding of disease processes, it may also bring unexpected difficulties.”
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