Disability improvement as a clinically relevant outcome in clinical trials of relapsing forms of multiple sclerosis

Mult Scler. 2021 Dec;27(14):2219-2231. doi: 10.1177/13524585211000280. Epub 2021 Mar 26.

Abstract

Background: Disease-modifying therapies (DMTs) can reduce the risk of disability worsening in patients with relapsing forms of multiple sclerosis (RMS). High-efficacy DMTs can lead to confirmed or sustained disability improvement (CDI and SDI).

Objective and methods: Post hoc analyses of data from the TRANSFORMS, FREEDOMS, and FREEDOMS II trials and their extensions assessed the effects of fingolimod (0.5-1.25 mg/day) on stabilizing or improving disability over ⩽8 years in participants with RMS. CDI and SDI rates were compared between participants initially randomized to fingolimod, interferon (IFNβ-1a), or placebo.

Results: At 8 years' follow-up in TRANSFORMS, 35.1% (95% confidence interval [CI], 28.2%-43.1%) of assessed participants in the IFNβ-1a-fingolimod switch group and 41.9% (36.6%-47.6%) on continuous fingolimod experienced CDI; disability did not worsen in approximately 70%. Similar results were seen in the combined FREEDOMS population. Proportionally fewer TRANSFORMS participants achieved SDI in the IFNβ-1a-fingolimod switch group than on continuous fingolimod (5.4% [3.0%-9.5%] vs 14.2% [10.8%-18.4%], p = 0.01).

Conclusion: CDI and SDI are outcomes of interest for clinical trials and for long-term follow-up of participants with RMS. Monitoring CDI and SDI in addition to disability worsening may facilitate understanding of the therapeutic benefit of RMS treatments.

Keywords: Disease-modifying therapies; confirmed disability improvement; fingolimod; multiple sclerosis; outcome measurement; relapsing/remitting.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fingolimod Hydrochloride / therapeutic use
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Interferon-beta / therapeutic use
  • Multiple Sclerosis*
  • Multiple Sclerosis, Relapsing-Remitting* / drug therapy

Substances

  • Immunosuppressive Agents
  • Interferon-beta
  • Fingolimod Hydrochloride