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Open Access 01-04-2014 | Review Article

Teriflunomide and Its Mechanism of Action in Multiple Sclerosis

Authors: Amit Bar-Or, Andrew Pachner, Francoise Menguy-Vacheron, Johanne Kaplan, Heinz Wiendl

Published in: Drugs | Issue 6/2014

Abstract

Treatment of multiple sclerosis (MS) is challenging: disease-modifying treatments (DMTs) must both limit unwanted immune responses associated with disease initiation and propagation (as T and B lymphocytes are critical cellular mediators in the pathophysiology of relapsing MS), and also have minimal adverse impact on normal protective immune responses. In this review, we summarize key preclinical and clinical data relating to the proposed mechanism of action of the recently approved DMT teriflunomide in MS. Teriflunomide selectively and reversibly inhibits dihydro-orotate dehydrogenase, a key mitochondrial enzyme in the de novo pyrimidine synthesis pathway, leading to a reduction in proliferation of activated T and B lymphocytes without causing cell death. Results from animal experiments modelling the immune activation implicated in MS demonstrate reductions in disease symptoms with teriflunomide treatment, accompanied by reduced central nervous system lymphocyte infiltration, reduced axonal loss, and preserved neurological functioning. In agreement with the results obtained in these model systems, phase 3 clinical trials of teriflunomide in patients with MS have consistently shown that teriflunomide provides a therapeutic benefit, and importantly, does not cause clinical immune suppression. Taken together, these data demonstrate how teriflunomide acts as a selective immune therapy for patients with MS.

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Title: Teriflunomide and Its Mechanism of Action in Multiple Sclerosis
Authors: Amit Bar-Or
Andrew Pachner
Francoise Menguy-Vacheron
Johanne Kaplan
Heinz Wiendl
Publication date: 01-04-2014
Publisher: Springer International Publishing
Published in: Drugs / Issue 6/2014
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI: https://doi.org/10.1007/s40265-014-0212-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Teriflunomide and Its Mechanism of Action in Multiple Sclerosis

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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