Alemtuzumab versus interferon beta-1a in early multiple sclerosis

Abstract

Introduction: Monoclonal antibodies (MAbs) have the potential to revolutionize multiple sclerosis (MS) therapeutics. The availability of natalizumab (Tysabri; Biogen Idec, Cambridge, MA) as the fi rst MAb treatment for MS approved by the US Food and Drug Administration (FDA) has been a signifi cant advancement in MS therapeutics [1]. Targeted against the alpha-4 integrin on leukocytes, natalizumab blocks migration of pathogenic lymphocytes into the central nervous system. Natalizumab currently is used as a second-line agent for relapsing forms of MS. Rituximab (Rituxan; Genentech, South San Francisco, CA, and Biogen Idec) and daclizumab (Zenapax; Roche Laboratories, Nutley, NJ) are two additional MAbs that appear to be promising treatment options for relapsing MS [2–5]. Rituximab and daclizumab are directed against CD20+ B cells and CD25+ T cells, respectively. Hauser et al. [4] reported that intravenous rituximab given in two doses had signifi cant benefi cial effect on clinical and MRI-visualized disease activity that was maintained over 48 weeks. Daclizumab administered every 4 weeks appeared equally promising in clinical effi cacy in MS [2,3,5]. Alemtuzumab (Campath; Genzyme, Cambridge, MA), a MAb that targets CD52 on lymphocytes and monocytes, is being explored as a potential agent in MS treatment. Alemtuzumab has FDA approval for B-cell chronic lymphocytic leukemia [6]. In this report, we review a phase 2 clinical trial of alemtuzumab in MS and revisit the advantages and potential serious side effects of MAbs for treating MS.