No abstract

This study does not support the use of cell counts as biomarkers for identifying patients at greater risk of active disease following treatment with alemtuzumab.

GSK2618960 was well tolerated and blocked IL-7 receptor signalling upon full target engagement. Although there was no discernible impact on peripheral T cell subsets in healthy subjects, GSK2618960 may effectively modulate the autoinflammatory activity of pathogenic T cells in diseased tissue. A relatively short half-life is likely the result of target-mediated rather than ADA-mediated clearance.

Alemtuzumab was first used in multiple sclerosis in 1991. It is a monoclonal antibody which is directed against CD52, a protein of unknown function on lymphocytes. Alemtuzumab causes a lymphopenia, following which homeostatic reconstitution leads to prolonged alteration of the immune repertoire. This reduces the risk of relapse and disability accumulation in multiple sclerosis; it is the only drug to show superiority over interferon β-1a in disability outcomes in a monotherapy phase III trial. It should be used with a parallel risk management programme to identify the principal adverse effects of alemtuzumab, especially secondary autoimmunity months or years later, mainly against the thyroid but also immune thrombocytopenia. This review charts the development of alemtuzumab as a drug for multiple sclerosis and summarizes the latest clinical trial data.