Alemtuzumab for the treatment of relapsing-remitting multiple sclerosis

Immunotherapy. 2014;6(3):249-59. doi: 10.2217/imt.14.7.

Abstract

Alemtuzumab, a humanized monoclonal antibody that targets CD52, was recently approved in the EU and Canada for the treatment of patients with active relapsing-remitting multiple sclerosis. Alemtuzumab induces rapid depletion of circulating B- and T-lymphocytes followed by repopulation that leads to a distinctive lymphocyte profile, including an increased proportion of regulatory T-lymphocytes and memory B- and T-lymphocytes. In early open-label studies, alemtuzumab treatment reduced the number of clinical relapses and new MRI lesions in participants with secondary progressive MS. However, most participants had continued worsening of disability, which led to the evaluation of alemtuzumab in patients with early stages of disease in the Genzyme (MA, USA)-sponsored clinical development program in MS. In one Phase II and two Phase III trials, alemtuzumab reduced the number of clinical relapses versus the active comparator, subcutaneous IFN-β-1a, in treatment-naive and treatment-experienced participants with relapsing-remitting multiple sclerosis. Two of these trials showed reduction in risk of confirmed worsening of disability, and all showed reduction in cerebral atrophy. Safety issues include infusion reactions that are mitigated by pretreatment with corticosteroids in addition to symptomatic management with antihistamines; mild to moderate infections; and autoimmune adverse events. In this context, post-marketing risk mitigation strategies will be needed so that potential adverse events can be identified and managed early and effectively.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Alemtuzumab
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / chemistry
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antigens, CD / immunology
  • Antigens, Neoplasm / immunology
  • Antirheumatic Agents / adverse effects
  • Antirheumatic Agents / chemistry
  • Antirheumatic Agents / pharmacokinetics
  • Antirheumatic Agents / therapeutic use*
  • Atrophy
  • Autoimmune Diseases / etiology
  • B-Lymphocyte Subsets / immunology
  • Brain / pathology
  • CD52 Antigen
  • Clinical Trials, Phase II as Topic / statistics & numerical data
  • Clinical Trials, Phase III as Topic / statistics & numerical data
  • Disability Evaluation
  • Female
  • Glycoproteins / immunology
  • Histamine Antagonists / therapeutic use
  • Humans
  • Immunologic Factors / adverse effects
  • Immunologic Factors / chemistry
  • Immunologic Factors / pharmacokinetics
  • Immunologic Factors / therapeutic use*
  • Immunologic Memory
  • Infections / etiology
  • Interferon beta-1a
  • Interferon-beta / therapeutic use
  • Lymphocyte Depletion
  • Male
  • Multicenter Studies as Topic / statistics & numerical data
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Multiple Sclerosis, Relapsing-Remitting / pathology
  • Neoplasms / etiology
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Single-Blind Method
  • T-Lymphocyte Subsets / immunology
  • Treatment Outcome

Substances

  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD
  • Antigens, Neoplasm
  • Antirheumatic Agents
  • CD52 Antigen
  • CD52 protein, human
  • Glycoproteins
  • Histamine Antagonists
  • Immunologic Factors
  • Alemtuzumab
  • Interferon-beta
  • Interferon beta-1a