Background: In relapsing forms of Multiple Sclerosis, disability progression has been shown to be independent of relapses. A new concept in MS research has emerged, PIRA or Progression Independent of Relapse Activity. Expanded Disability Status Scale (EDSS) is a widely used scale for assessing disability but relies excessively on lower body mobility, neglecting other aspects of disability progression.
Objectives: To assess composite of confirmed disability accumulation (CDA), including EDSS scores, 9-hole peg test, and timed 25-foot walk, as it would be more comprehensive and sensitive assessment of disease progression.
Methods: Using results from the OPTIMUM study, time to first composite 12-week CDA was compared between ponesimod 20mg and teriflunomide 14mg. Additional analyses were conducted to assess PIRA. Hazard ratios and 95% confidence intervals were calculated to test the treatment effect between the two compounds.
Results: At week 108, composite CDA was reached during the study by 18.2% and 24.0% of subjects in the ponesimod 20mg and teriflunomide 14mg groups, respectively. The relative risk of an event was estimated to be 24% lower with ponesimod 20 mg, with the difference being statistically significant at a significance level of 5% (hazard ratio: .76 95% CI = 0.59 – 0.98; p-value = 0.0346). The sensitivity analyses for PIRA and non-relapsing subjects yielded similar results.
Conclusions: Using a more comprehensive measure of disability worsening, a statistically significant difference and clinically meaningful treatment effect of ponesimod versus teriflunomide was established. This treatment effect is also present when considering disability worsening independent of relapse activity.
Please login to see your profile content