Alemtuzumab as Treatment for Multiple Sclerosis

Abstract

Alemtuzumab, the first monoclonal antibody to be used as a therapy and the first to be humanized, was introduced into the treatment of multiple sclerosis in 1991 after its successful use in hematology, oncology, and transplantation medicine. One phase 2 and two phase 3 trials of this lymphocyte-depleting agent have established alemtuzumab's superior efficacy to interferon β-1a over the short term (2-3 years) with greater relapse rate reduction, reduced accumulation of disability, and more frequent sustained improvement in disability. Longer-term extension studies show durable effects on slowing cerebral atrophy over 6 years and maintained low relapse rates over 10 years, despite roughly half of patients not needing further dosing. Homeostatic proliferation of residual T cells after alemtuzumab-induced lymphopenia is probably responsible for its most common side effects: secondary autoimmunity 1 or 2 years after the last infusion of alemtuzumab affecting the thyroid gland (30% of patients), platelets (1%), or renal glomeruli (0.1%). With the prerequisite of patient and physician adherence to a prolonged safety-monitoring protocol, alemtuzumab offers durable high efficacy from infrequent dosing.