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J Neurol Neurosurg Psychiatry. 2018 Dec;89(12):1266-1271. doi: 10.1136/jnnp-2017-317411. Epub 2018 Jul 10.

Cladribine: mechanisms and mysteries in multiple sclerosis.

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The Blizard Institute (Neuroscience), Queen Mary University of London, Barts and the London School of Medicine and Dentistry, London, UK
The Blizard Institute (Neuroscience), Queen Mary University of London, Barts and the London School of Medicine and Dentistry, London, UK.
Emergency Care and Acute Medicine Clinical Academic Group Neuroscience, Barts Health NHS Trust, The Royal London Hospital, London, UK.



The aims of this manuscript were to review the evidence for the efficacy and safety of cladribine in multiple sclerosis (MS) and to review the molecular and cellular mechanisms by which cladribine acts as a disease-modifying therapy in MS.


This is a narrative review of the available clinical and preclinical data on the use of cladribine in MS.


Clinical trial data argue strongly that cladribine is a safe and effective therapy for relapsing MS and that it may also be beneficial in progressive MS. The pharmacology of cladribine explains how it is selectively toxic towards lymphocytes. Immunophenotyping studies show that cladribine depletes lymphocyte populations in vivo with a predilection for B cells. In vitro studies demonstrate that cladribine also exerts immunomodulatory influences over innate and adaptive immunity.


Cladribine is a safe and effective form of induction therapy for relapsing MS. Its mechanism of benefit is not fully understood but the most striking action is selective, long-lasting, depletion of B lymphocytes with a particular predilection for memory B cells. The in vivo relevance of its other immunomodulatory actions is unknown. The hypothesis that cladribine's action of benefit is to deplete memory B cells is important: if correct, it implies that selective targeting of this cell population and sparing of other lymphocytes could modify disease activity without predisposing to immunosuppression-related complications.


multiple sclerosis


Conflict of interest statement

Competing interest: DB reports being a founder and consultant to Canbex Therapeutics and receiving research funds from Canbex Therapeutics, Sanofi-Genzyme and Takeda in the past 3 years. GG reports receiving fees for participation in the advisory board for AbbVie Biotherapeutics, Biogen, Canbex, Ironwood, Novartis, Merck, Inc, Merck Serono, Roche, Sanofi Genzyme, Synthon, Teva and Vertex; speaker fees from AbbVie, Biogen, Bayer HealthCare, Genzyme, Merck Serono, Sanofi-Aventis and Teva and research support from Biogen, Genzyme, Ironwood, Merck, Inc, Merck Serono and Novartis. KS reports being a principal investigator of trials sponsored by Novartis, Roche, Teva and Medday; involved in trials sponsored by Biogen, Sanofi-Genzyme, BIAL, Cytokinetics and Canbex and receiving speaking honoraria for lecturing and advisory activity and/or meeting support from Biogen, Merck, Inc, Merck Serono, Novartis, Roche, Sanofi-Genzyme and Teva. All authors have presented posters at the European Congress for Treatment and Research in Multiple Sclerosis (ECTRIMS) annual congress.

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