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Background Alemtuzumab, a humanized monoclonal antibody that targets CD52 on lymphocytes and monocytes, may be an effective treatment for early multiple sclerosis.
Methods In this phase 2, randomized, blinded trial involving previously untreated, early, relapsing–remitting multiple sclerosis, we assigned 334 patients with scores of 3.0 or less on the Expanded Disability Status Scale and a disease duration of 3 years or less to receive either subcutaneous interferon beta-1a (at a dose of 44 µg) three times per week or annual intravenous cycles of alemtuzumab (at a dose of either 12 mg or 24 mg per day) for 36 months. In September 2005, alemtuzumab therapy was suspended after immune thrombocytopenic purpura developed in three patients, one of whom died. Treatment with interferon beta-1a continued throughout the study.
Results Alemtuzumab significantly reduced the rate of sustained accumulation of disability, as compared with interferon beta-1a (9.0% vs. 26.2%; hazard ratio, 0.29; 95% confidence interval [CI], 0.16 to 0.54; P<0.001) and the annualized rate of relapse (0.10 vs. 0.36; hazard ratio, 0.26; 95% CI, 0.16 to 0.41; P<0.001). The mean disability score on a 10-point scale improved by 0.39 point in the alemtuzumab group and worsened by 0.38 point in the interferon beta-1a group (P<0.001). In the alemtuzumab group, the lesion burden (as seen on T2-weighted magnetic resonance imaging) was reduced, as compared with that in the interferon beta-1a group (P=0.005). From month 12 to month 36, brain volume (as seen on T1-weighted magnetic resonance imaging) increased in the alemtuzumab group but decreased in the interferon beta-1a group (P=0.02). Adverse events in the alemtuzumab group, as compared with the interferon beta-1a group, included autoimmunity (thyroid disorders [23% vs. 3%] and immune thrombocytopenic purpura [3% vs. 1%]) and infections (66% vs. 47%). There were no significant differences in outcomes between the 12-mg dose and the 24-mg dose of alemtuzumab.
Conclusions In patients with early, relapsing–remitting multiple sclerosis, alemtuzumab was more effective than interferon beta-1a but was associated with autoimmunity, most seriously manifesting as immune thrombocytopenic purpura. The study was not powered to identify uncommon adverse events. (ClinicalTrials.gov number, NCT00050778
[ClinicalTrials.gov]
.)
Source Information
The members of the writing group (Alasdair J. Coles, Ph.D., F.R.C.P., and D. Alastair S. Compston, F.Med.Sci., Ph.D., University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom; Krzysztof W. Selmaj, M.D., Ph.D., Department of Neurology, Medical University of Lodz, Lodz, Poland; and Stephen L. Lake, Sc.D., Susan Moran, M.D., M.S.C.E., David H. Margolin, M.D., Ph.D., Kim Norris, B.Sc., and P.K. Tandon, Ph.D., Genzyme, Cambridge, MA) assume responsibility for the overall content and integrity of the article.
Address reprint requests to Drs. Coles and Compston at the Department of Neurology, Box 165, Addenbrooke's Hospital, Cambridge CB2 2QQ, United Kingdom, or at ajc1020{at}medschl.cam.ac.uk or alastair.compston{at}medschl.cam.ac.uk.
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