title: The outlook for alemtuzumab in multiple sclerosis.
abstract: Alemtuzumab is a humanized anti-CD52 monoclonal antibody. Treatment in humans results in a rapid, profound, and prolonged B- and T-cell lymphopenia. Subsequently, lymphocyte reconstitution by homeostatic mechanisms alters the composition, phenotype, and function of T-cell subsets, thus allowing the immune system to be 'reset'. One phase II and two phase III randomized, multicenter, single-blinded (outcomes assessor) clinical trials of alemtuzumab in relapsing-remitting multiple sclerosis have now been completed. Against an active comparator and the current first-line therapy for relapsing-remitting multiple sclerosis (interferon-beta), alemtuzumab showed a significant reduction in annualized relapse rate as well as a significant reduction in the accumulation of disability. These outcomes are sustained over at least 5 years following treatment. The most common adverse effects are mild infusion reactions, an increased incidence of mild-to-moderate severity infections and secondary autoimmunity. The latter is observed in a third of treated patients, commonly thyroid disease but other target cells have been described including cytopenias. Marketing authorization applications have been submitted for the use of alemtuzumab in multiple sclerosis to the Food and Drug Administration and the European Medicines Agency, with licensing expected in 2013. Here, we discuss the outlook for alemtuzumab in multiple sclerosis in light of the currently available therapies, outcomes of and lessons learnt from clinical trials, and the overall position of monoclonal antibodies in modern treatment strategies.
authors.affiliation: Department of Clinical Neurosciences, Addenbrooke's Hospital, University of Cambridge, Box 165, Cambridge, CB2 0QQ, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Williams
authors.forename: Alasdair
authors.initials: A
authors.lastname: Coles
authors.forename: Laura
authors.initials: L
authors.lastname: Azzopardi
mesh_terms: D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008231:Lymphopenia / Q000139:chemically induced; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab