title: Alemtuzumab in Multiple Sclerosis: Mechanism of Action and Beyond.
abstract: Alemtuzumab is a humanized monoclonal antibody against CD52 (cluster of differentiation 52) and is approved for the therapy of relapsing-remitting multiple sclerosis. The application of alemtuzumab leads to a rapid, but long-lasting depletion predominantly of CD52-bearing B and T cells with reprogramming effects on immune cell composition resulting in the restoration of tolerogenic networks. Alemtuzumab has proven high efficacy in clinical phase II and III trials, where interferon β-1a was used as active comparator. However, alemtuzumab is associated with frequent and considerable risks. Most importantly secondary autoimmune disease affects 30%-40% of patients, predominantly impairing thyroid function. Extensive monitoring and early intervention allow for an appropriate risk management. However, new and reliable biomarkers for individual risk stratification and treatment response to improve patient selection and therapy guidance are a significant unmet need. Only a deeper understanding of the underlying mechanisms of action (MOA) will reveal such markers, maximizing the best potential risk-benefit ratio for the individual patient. This review provides and analyses the current knowledge on the MOA of alemtuzumab. Most recent data on efficacy and safety of alemtuzumab are presented and future research opportunities are discussed.
authors.affiliation: Department of Neurology, University of Muenster, Muenster 48149, Germany. tobias.ruck@ukmuenster.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Ruck
authors.affiliation: Department of Neurology, University of Muenster, Muenster 48149, Germany. stefan.bittner@ukmuenster.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bittner
authors.affiliation: Department of Neurology, University of Muenster, Muenster 48149, Germany. heinz.wiendl@ukmuenster.de.
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.affiliation: Department of Neurology, University of Muenster, Muenster 48149, Germany. sven.meuth@ukmuenster.de.
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
mesh_terms: D000074323:Alemtuzumab; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000074323:Alemtuzumab
keywords: CD52; alemtuzumab; experimental autoimmune encephalomyelitis (EAE); mechanism of action; multiple sclerosis; secondary autoimmune disease