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The Use of Oral Disease-Modifying Therapies in Multiple Sclerosis

  • Demyelinating Disorders (DN Bourdette and M Cameron, Section Editors)
  • Published:
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Abstract

Three oral disease-modifying drugs—fingolimod, teriflunomide, and dimethyl fumarate (DMF)—are available for treatment of relapsing forms of multiple sclerosis (MS). All three agents were approved in the last decade, primarily on the basis of a moderate to substantial reduction in the occurrence of MS relapses and central nervous system lesion formation detected by MRI. In the trials leading to approval, the first oral disease-modifying drug, fingolimod, reduced the annualized relapse rate (ARR) from 0.40 in placebo-treated patients to 0.18 (FREEDOMS) and from 0.33 in patients treated with interferon β1a intramuscularly to 0.16 (TRANSFORMS). Teriflunomide, approved on the basis of the two placebo-controlled trials TEMSO and TOWER, demonstrated a reduction in the ARR from 0.54 to 0.37 and from 0.50 to 0.32 respectively. The latest oral MS medication, approved in 2014, is DMF, which had been used in a different formulation for treatment of psoriasis for decades. In the 2-year DEFINE study, the proportion of patients with a relapse was reduced to 27 %, compared with 46 % in placebo arm, whereas in the CONFIRM trial, the ARR was reduced from 0.40 (placebo) to 0.22 in the DMF-treated group of patients. In this review, we will elucidate the mechanisms of action of these three medications and compare their efficacy, safety, and tolerability as a practical guideline for their use. We will further discuss effects other than relapse reduction these small molecules may exert, including potential activities within the central nervous system, and briefly summarize emerging data on new oral MS drugs in clinical development.

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Author notes

  1. Benedikt Kretzschmar

    Present address: Doctor’s Office Knaak/Christmann/Wüstenhagen of Neurology and Psychiatry, 34346, Hann. Münden, Germany

Authors and Affiliations

  1. Department of Neurology, University Medical Center, 37075, Göttingen, Germany

    Benedikt Kretzschmar, Hannah Pellkofer & Martin S. Weber

  2. Institute of Neuropathology, University Medical Center, 37075, Göttingen, Germany

    Hannah Pellkofer & Martin S. Weber

  3. Department of Neuropathology, Department of Neurology, University Medical Center, Georg August University, Robert-Koch-Str. 40, 37099, Göttingen, Germany

    Martin S. Weber

Authors
  1. Benedikt Kretzschmar
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  2. Hannah Pellkofer
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  3. Martin S. Weber
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Correspondence to Martin S. Weber.

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Conflict of Interest

Benedikt Kretzschmar declares no conflict of interest.

Dr. Pellkofer reports non-financial support from Novartis, personal fees and non-financial support from Biogen idec, personal fees and non-financial support from Teva, personal fees and non-financial support from Bayer Schering, outside the submitted work.

Dr. Weber is serving as an editor for PLoS One. He received travel funding and/or speaker honoraria from Biogen-Idec, Merck Serono, Novartis, Roche, TEVA and Bayer. He receives research support from the National Multiple Sclerosis Society (NMSS; PP 1660), the Deutsche Forschungsgemeinschaft (DFG; WE 3547/4-1), from Novartis, TEVA, Biogen-Idec, Roche, Merck and the ProFutura Programm of the Universitätsmedizin Göttingen.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Demyelinating Disorders

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Kretzschmar, B., Pellkofer, H. & Weber, M.S. The Use of Oral Disease-Modifying Therapies in Multiple Sclerosis. Curr Neurol Neurosci Rep 16, 38 (2016). https://doi.org/10.1007/s11910-016-0639-4

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  • DOI: https://doi.org/10.1007/s11910-016-0639-4

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