Der Nervenarzt

, Volume 83, Issue 4, pp 487–501 | Cite as

Alemtuzumab: eine weitere Chance zur Therapie der Multiplen Sklerose

  • T. Menge
  • B.C. Kieseier
  • C. Warnke
  • O. Aktas
  • H.-P. Hartung
Aktuelles aus Diagnostik und Therapie
  • 322 Downloads

Zusammenfassung

Alemtuzumab ist ein humanisierter monoklonaler Antikörper, der an das Zelloberflächenantigen CD52 bindet. CD52 wird auf einer Vielzahl von Zellen der lymphomonozytären Zellreihe exprimiert, nicht jedoch auf Vorläuferzellen. Alemtuzumab führt zu einer raschen und langanhaltenden Depletion von CD52-tragenden Zellen aus dem Blut. In deren Folge kommt es zu einer schrittweisen Rekonstitution, wobei anfangs aktivierte B-Lymphozyten und regulatorische T-Lymphozyten überwiegen.

Alemtuzumab ist zunächst in zwei offenen Therapiestudien an 58 und 39 Patienten mit Multipler Sklerose (MS) und danach aufgrund der sehr vielversprechenden Ergebnisse in einer ambitionierten klinischen Phase-II-Studie gegen subkutan appliziertes Interferon β-1a getestet worden. Dabei zeigte sich, dass Alemtuzumab nicht nur sehr effizient Schubrate und Behinderungsprogression reduzierte, sondern sogar zu einer Verbesserung des funktionellen Defizites führen konnte. Trotz langanhaltender Lymphopenie kam es nicht vermehrt zu schweren oder opportunistischen Infektionen. Wohl aber erlitten bis zu 30% der Patienten antikörpervermittelte Autoimmunerkrankungen, zumeist Schilddrüsenerkrankungen, aber auch immunvermittelte thrombozytopenische Purpura und Goodpasture-Syndrom.

In dieser Übersichtsarbeit werden die präklinische und klinische Entwicklung von Alemtuzumab dargestellt sowie Wirkmechanismen und die Pathogenese der Autoimmunphänomene diskutiert.

Schlüsselwörter

Multiple Sklerose Alemtuzumab Phase-II-Studie Autoimmunerkrankungen Pathogenese 

Alemtuzumab: a further option for treatment of multiple sclerosis

Summary

Alemtuzumab is a humanized monoclonal therapeutic antibody that targets the CD52 antigen which s expressed on most cells of the lymphoid lineage, exclusive of precursors. Alemtuzumab rapidly depletes CD52+ cells from the peripheral blood. This depletion is long-lasting, and cells repopulate in a specific pattern with B cells and regulatory T cells peaking first. Alemtuzumab was examined for clinical utility in two open-labelled intervention trials in multiple sclerosis (MS). Because of very promising results its clinical efficacy was further explored in a clinical phase-II trial using s.c. interferon beta-1a as the active comparator. Severe or opportunistic infections were surprisingly rare given the long-term lymphopenia. However, up to 30% of patients developed some antibody-mediated autoimmunity. The thyroid gland was the most frequently affected organ. Immune-mediated thrombocytopenic purpura and Goodpasture’s syndrome were additionally observed.

This review summarizes the pre-clinical and clinical development of alemtuzumab and discusses potential modes of action as well as the pathogenetic link to the treatment emergent autoimmune phenomena.

Keywords

Multiple sclerosis Alemtuzumab Clinical trial phase II  Autoimmune diseases Pathogenesis 

Notes

Interessenkonflikte

Der korrespondierende Autor weist auf folgende Beziehungen hin: T. M. erhielt Honorare und Reisekostenzuschüsse von Bayer Healthcare, Biogen Idec, Merck Serono. CW hat keine Interessenkonflikte. B.C.K, O.A. und H.-P.H. erhielten in der Vergangenheit nach Genehmigung durch den Ärztlichen Direktor des Universitätsklinikums Düsseldorf und den Rektor der Heinrich-Heine-Universität Vortrags- bzw. Beratungshonorare der Hersteller der im Artikel erwähnten Präparate: (Bayer Schering, Biogen Idec, Merck-Serono, Novartis, TEVA/Sanofi Aventis) sowie Genentech (H.-P.H.).

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • T. Menge
    • 1
  • B.C. Kieseier
    • 1
  • C. Warnke
    • 1
  • O. Aktas
    • 1
  • H.-P. Hartung
    • 1
  1. 1.Neurologische KlinikUniversitätsklinikum DüsseldorfDüsseldorfDeutschland

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