Abstract
Alemtuzumab is a humanized monoclonal antibody against CD52 (cluster of differentiation 52) and is approved for the therapy of relapsing-remitting multiple sclerosis. The application of alemtuzumab leads to a rapid, but long-lasting depletion predominantly of CD52-bearing B and T cells with reprogramming effects on immune cell composition resulting in the restoration of tolerogenic networks. Alemtuzumab has proven high efficacy in clinical phase II and III trials, where interferon β-1a was used as active comparator. However, alemtuzumab is associated with frequent and considerable risks. Most importantly secondary autoimmune disease affects 30%–40% of patients, predominantly impairing thyroid function. Extensive monitoring and early intervention allow for an appropriate risk management. However, new and reliable biomarkers for individual risk stratification and treatment response to improve patient selection and therapy guidance are a significant unmet need. Only a deeper understanding of the underlying mechanisms of action (MOA) will reveal such markers, maximizing the best potential risk-benefit ratio for the individual patient. This review provides and analyses the current knowledge on the MOA of alemtuzumab. Most recent data on efficacy and safety of alemtuzumab are presented and future research opportunities are discussed.
Highlights
Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS)characterized by inflammation, demyelination, and axonal degeneration
Alemtuzumab is a humanized monoclonal antibody targeting CD52, a surface molecule with largely unknown function and which is predominantly expressed on B and T cells [1]
This review focuses on the mechanisms of action underlying clinical efficacy and the adverse event profile of alemtuzumab
Summary
Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS). There is often only limited knowledge on the mechanisms of action underlying the effects and adverse events of these therapeutic agents, what might be especially true for alemtuzumab. Drug Administration (FDA) in November 2014, alemtuzumab is approved in over 30 countries for the therapy of relapsing-remitting multiple sclerosis (RRMS). Alemtuzumab demonstrated superiority to subcutaneous (s.c.) interferon β-1a (IFNβ-1a), an established disease-modifying therapy (DMT) for RRMS. The high efficacy of alemtuzumab, with remarkable effects on clinical and radiological disease outcome parameters is offset by frequent and significant adverse events. 30%–40% of patients develop secondary autoimmune diseases predominantly affecting thyroid, kidney and thrombocytic function [2]. This review focuses on the mechanisms of action underlying clinical efficacy and the adverse event profile of alemtuzumab. The newest data on efficacy and safety of alemtuzumab are summarized, and an outlook on future research opportunities is given
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