Alemtuzumab is a mAb that binds to CD52, an epitope common to most cells within the immune system. Treatment with this agent essentially results in an antibody-mediated ablation of the circulating immune system. Alemtuzumab binds to B and T lymphocytes, resulting in antibody-dependent cell lysis, and subsequent elimination from the bone marrow and blood, with the effect lasting up to 16 months. This agent appears to rapidly and profoundly establish both clinical and radiographic remission of MS; however, alemtuzumab has been associated with the risk of developing new autoimmune disorders (autoimmunity), including thyroiditis, idiopathic thrombocytopenic purpura and Goodpasture's syndrome. Cossburn and colleagues found that the cumulative risk of autoimmunity in MS following the use of alemtuzumab was 22.2%, most frequent between 12 and 18 months following the first dose and evident for up to 5 years [Cossburn et al. 2011].

Other adverse events associated with alemtuzumab include infections, increased cancer risk, organ toxicity and infusion-associated hypersensitivity reactions with potentially resultant neutralizing antibodies. Studies of alemtuzumab in the treatment of patients with RRMS and SPMS have suggested efficacy in the suppression of ARR, but with variable results in preventing progression of disability, depending on stages of the disease [Corboy et al. 2010].

The phase II trial CAMMS223 compared alemtuzumab (12 or 24 mg intravenously on 5 consecutive days during the first month and on 3 consecutive days at months 12 and 24) with IFN-β1a, 44 μg subcutaneously three times a week. Alemtuzumab demonstrated a decrease in sustained disability (75% at 12 mg dose and 67% at 24 mg dose) and a decrease in relapse rate (69% at 12 mg and 79% at 24 mg) compared with IFN-β1a subcutaneously [Panitch et al. 2008].

Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis Study 1 (CARE MS I), a 2 year phase III trial comparing alemtuzumab with subcutaneous IFN-β1a in treatment-naïve patients showed a reduction in relapse rate by 55% but did not show statistical significance regarding slowing disease process. A second phase III trial (CARE MS II) is currently in progress.