Lessons from clinical trials of alemtuzumab in multiple sclerosis

Alemtuzumab is a humanised monoclonal antibody that selectively targets CD52 leucocytes. Originally developed in the Cambridge Pathology laboratory (hence its earlier name Campath 1-H), subcutaneous injection of alemtuzumab is currently licensed as a second or third line therapy of chronic lymphocytic leukaemia, and has also been used as an induction agent in renal transplantation costing an average of US $2000 per treatment course. Alemtuzumab causes profound and long term depletion of lymphocytes and after a single subcutaneous dose, CD4+and CD8+T-cells, CD3-/ CD56+NK cells, CD3+/CD56+T-cells and CD19+/CD5B-cells were all decreased to o25% of baseline at 9 months (Lundin et al., 2004). B-cell suppression generally recovers earlier than T-cells, usually within 3–4 months; and patients with rheumatoid arthritis remained lymphopenic 12 years after a single dose of alemtuzumab, indicating that its lymphocytotoxic effect results in permanent alteration in T-and B-lymphocyte subsets (Anderson et al., 2012). Alemtuzumab was first introduced to the therapeutics of multiple sclerosis (MS) by the Cambridge neurologists in the 1990s. After intravenous alemtuzumab, the disease activity was found to persist for several weeks before stabilisation of clinical symptoms in a small group of 27 MS patients (Coles et al., 1999). Infusion-associated reactions after alemtuzuab were caused by cytokine release syndrome, and necessitated use of high dose corticosteroids, anti-