title: Alemtuzumab therapy for multiple sclerosis.
abstract: Alemtuzumab is a humanized monoclonal antibody that is administered daily for 5 days, and then no further therapy is required for 12 months. It causes rapid and prolonged lymphocyte depletion; the consequent homeostatic reconstitution leads to a radically reformed lymphocyte pool with a relative increase in regulatory T cells and expansion of autoreactive T cells. Although previously licensed for the treatment of B-cell chronic lymphocytic leukemia, it is now been considered for licensing in the treatment of multiple sclerosis (MS). From a disappointing experience with alemtuzumab in progressive MS, Alastair Compston and I argued that immunotherapies should be given early in the course of the disease. In a unique program of drug development in MS, alemtuzumab has been compared in 1 phase 2 trial and 2 phase 3 trials with the active comparator interferon beta-1a. In all trials, alemtuzumab was more effective in suppressing relapses than interferon beta-1a. In one phase 2 and one phase 3 trial, alemtuzumab also reduced the risk of accumulating disability compared with interferon beta-1a. Indeed, alemtuzumab treatment led to an improvement in disability and a reduction in cerebral atrophy. The safety issues are infusion-associated reactions largely controlled by methylprednisolone, antihistamines, and antipyretics; mild-to-moderate infections (with 3 opportunistic infections from the open-label experience: 1 case each of spirochaetal gingivitis, pyogenic granuloma, and Listeria meningitis); and autoimmunity. Usually autoimmunity is directed against the thyroid gland, but causes (1 %) immune thrombocytopenia, and in a few cases antiglomerular basement membrane syndrome. Alemtuzumab is an effective therapy for early relapsing-remitting MS, offering disability improvement at least to 5 years after treatment. Its use requires careful monitoring so that potentially serious side effects can be treated early and effectively.
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, CB2 0QQ, UK. Ajc1020@medschl.cam.ac.uk
authors.forename: Alasdair J
authors.initials: AJ
authors.lastname: Coles
mesh_terms: D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D000074323:Alemtuzumab