title: [Alemtuzumab for relapsing-remitting multiple sclerosis. Results of two randomized controlled phase III studies].
abstract: In November 2012 the results of 2 clinical phase III trials were published which addressed the effects of alemtuzumab in patients with relapsing-remitting multiple sclerosis (MS). In the CARE-MS-I study patients with early untreated MS (EDSS ≤ 3.0, disease duration < 5 years) were included, whereas CARE-MS-II investigated the effects of alemtuzumab in patients with persisting disease activity under standard disease-modifying treatment (EDSS ≤ 5.0, disease duration < 10 years). These groups were compared to patients under treatment with frequently applied interferon β 1a (3 times  44 µg subcutaneous). Both studies clearly demonstrated a superiority of alemtuzumab compared to interferon in terms of reduction of relapse rate as well as the number of new or enlarging T2 lesions and gadolinium-enhancing lesions. Moreover, the CARE-MS-II study showed a significant delay in disease progression by alemtuzumab. The portfolio and the frequency of relevant side effects, such as infusion-related reactions, development of secondary autoimmunity or infections were within the expected range. Taken together these studies confirm the high anti-inflammatory efficacy of alemtuzumab and hence provide the first evidence of superiority of a monotherapy in direct comparison to standard disease-modifying treatment in two phase III trials in relapsing-remitting MS. These data in the context of the mode of action of alemtuzumab provide evidence for the relevance of immune cells, especially T cells, in the pathophysiology of MS. Experience with long-term effects of alemtuzumab, e.g. from the phase II extension trial as well as the side effect profile argue in favor of a sustained reprogramming of the immune system as a consequence of immune cell depletion by alemtuzumab.
authors.affiliation: Department für Neurologie - Klinik für Allgemeine Neurologie, Westfälische Wilhelms-Universität, Albert-Schweitzer-Campus 1, A10, 48149, Münster, Deutschland. luisaklotz@googlemail.com
authors.forename: L
authors.initials: L
authors.lastname: Klotz
authors.forename: S G
authors.initials: SG
authors.lastname: Meuth
authors.forename: B
authors.initials: B
authors.lastname: Kieseier
authors.forename: H
authors.initials: H
authors.lastname: Wiendl
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D015995:Prevalence; D012008:Recurrence; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D000074323:Alemtuzumab