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Alemtuzumab for the treatment of relapsing-remitting multiple sclerosis.
Immunotherapy. 2014; 6(3):249-59.I

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.

Authors+Show Affiliations

Mellen Center for Multiple Sclerosis Treatment & Research, Neurological Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.No affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

24762071

Citation

Hersh, Carrie M., and Jeffrey A. Cohen. "Alemtuzumab for the Treatment of Relapsing-remitting Multiple Sclerosis." Immunotherapy, vol. 6, no. 3, 2014, pp. 249-59.
Hersh CM, Cohen JA. Alemtuzumab for the treatment of relapsing-remitting multiple sclerosis. Immunotherapy. 2014;6(3):249-59.
Hersh, C. M., & Cohen, J. A. (2014). Alemtuzumab for the treatment of relapsing-remitting multiple sclerosis. Immunotherapy, 6(3), 249-59. https://doi.org/10.2217/imt.14.7
Hersh CM, Cohen JA. Alemtuzumab for the Treatment of Relapsing-remitting Multiple Sclerosis. Immunotherapy. 2014;6(3):249-59. PubMed PMID: 24762071.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alemtuzumab for the treatment of relapsing-remitting multiple sclerosis. AU - Hersh,Carrie M, AU - Cohen,Jeffrey A, PY - 2014/4/26/entrez PY - 2014/4/26/pubmed PY - 2015/1/30/medline SP - 249 EP - 59 JF - Immunotherapy JO - Immunotherapy VL - 6 IS - 3 N2 - 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. SN - 1750-7448 UR - https://www.unboundmedicine.com/medline/citation/24762071/Alemtuzumab_for_the_treatment_of_relapsing_remitting_multiple_sclerosis_ L2 - http://www.futuremedicine.com/doi/full/10.2217/imt.14.7?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -