Clinical Review State of the Art Review

Disease modifying therapies for relapsing multiple sclerosis

BMJ 2016; 354 doi: (Published 22 August 2016) Cite this as: BMJ 2016;354:i3518
  1. Dean M Wingerchuk, professor1,
  2. Brian G Weinshenker, professor2
  1. 1Department of Neurology, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ, 85259, USA
  2. 2Mayo Clinic, 200 1st Street SW, Rochester, MN, 55905, USA
  1. Correspondence to: D Wingerchuk wingerchuk.dean{at}


Multiple sclerosis (MS) is a common, disabling, putatively autoimmune neurological disease with worldwide distribution. It typically begins as a relapsing disorder that later evolves to a secondary progressive phase. Inflammatory and neurodegenerative mechanisms seem to operate in both phases, but their relative contributions and interactions are incompletely understood. Disease modifying therapies (DMTs) approved for relapsing multiple sclerosis interfere with a variety of immunological mechanisms to reduce rates of relapse, accumulation of disease burden measured by magnetic resonance imaging (MRI), and decline in neurological function over the two to three year duration of typical randomized controlled trials. Benefits of longer duration of therapy on disability are less clear, as data beyond three years are largely limited to observational studies. However, current DMTs do not slow accrual of disability once progressive multiple sclerosis is established. This review summarizes the evidence about the use of approved DMTs and examines how to individualize treatment despite the absence of validated biomarkers to guide drug selection. Methods such as stratifying patients on the basis of estimated risk for future disability, weighing patient specific factors and preferences, and using objective outcomes to adjudicate treatment success are discussed. Emerging drug therapies and strategies are also reviewed.


  • Contributors: DMW and BGW both designed, acquired data for, and drafted and revised the manuscript. Both authors approve of the final version to be published and agree to be accountable for all aspects of the work.

  • Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following interests: DMW receives research support from Alexion and TerumoBCT and personal compensation for consulting services provided to MedImmune for a neuromyelitis optica clinical trial adjudication panel; he has received personal compensation for consulting services from Chugai; BGW receives personal compensation for consulting services provided to MedImmune for a neuromyelitis optica clinical trial adjudication panel and for MS clinical trial DSMB membership from Novartis and Mitsubishi; he receives royalties from RSR Ltd and Oxford University for a patent on NMO-IgG as a diagnostic test for neuromyelitis optica and related disorders and has received personal compensation for consulting services from Elan, Chord Pharmaceuticals, GSK Pharmaceuticals, Ono Pharmaceuticals, and Chugai and MS clinical trial DSMB membership from Biogen.

  • Provenance and peer review: Commissioned; externally peer reviewed.

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