Disease-Modifying Treatment in Progressive Multiple Sclerosis

  • John Robert Ciotti
  • Anne Haney Cross
Multiple Sclerosis and Related Disorders (J Graves, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Multiple Sclerosis and Related Disorders


Purpose of review

Multiple sclerosis (MS) is an immune-mediated disorder that affects the central nervous system (CNS), often first affecting people in early adulthood. Although most MS patients have a relapsing-remitting course (RRMS) at disease onset, a substantial proportion later develop chronic progression, termed secondary progressive MS (SPMS). Approximately 10% of MS patients experience chronic progression from disease onset, termed primary progressive multiple sclerosis (PPMS). Although several disease-modifying treatment (DMT) options exist for relapsing forms of this disease, DMT options are few for progressive MS (PPMS and SPMS). Herein, we strive to define progressive MS, review major clinical trials aimed at progressive MS, and delineate potential strategies in the management of progressive MS.

Recent findings

In 2017, the first DMT for PPMS, the B lymphocyte-depleting monoclonal antibody, ocrelizumab, came to market. Ocrelizumab reduced 12-week confirmed disability progression (CDP) by 24% versus placebo. Siponimod, a selective sphingosine-1-phosphate receptor modulator, reduced 3-month CDP by 21% versus placebo in SPMS. Ibudilast slowed brain atrophy in PPMS and SPMS patients in a multicenter phase 2b study. Smaller early phase studies of alpha-lipoic acid and simvastatin each found slowing of rate of whole brain atrophy in SPMS patients.


Reasons now exist for optimism in the search for DMTs for progressive MS. It remains a challenge to identify outcome measures that accurately reflect the underlying pathology in progressive MS, which is less inflammatory and more degenerative than RRMS.


Progressive multiple sclerosis Disease-modifying therapy Neuroprotection Remyelination 



Anne Haney Cross was supported in part by the Manny and Rosalyn Rosenthal–Dr. John L. Trotter MS Center Chair in Neuroimmunology of the Barnes-Jewish Hospital Foundation.

Compliance with Ethical Standards

Conflict of Interest

John Robert Ciotti declares no conflict of interest.

Anne Haney Cross reports personal fees from Abbvie, Biogen, Bayer Healthcare, EMD Serono, Genzyme (Sanofi), Genentech (Roche), Novartis, and Teva Neuroscience.

Human and Animal Rights and Informed Consent

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

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Authors and Affiliations

  1. 1.Washington University in St. LouisSt. LouisUSA
  2. 2.St. LouisUSA

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