Abstract
Background: Confirmed disability improvement (CDI) is a frequently reported outcome in disease-modifying therapy (DMT) trials and observational studies in multiple sclerosis (MS). However, its clinical significance has not been established.
Objective: To evaluate the prognostic value of CDI events in MS and the potential utility of CDI as a treatment target. Patients from MSBase with adequate follow-up were included. The relationship of 12-month confirmed disability improvement events with patient and disease characteristics were evaluated. Generalised logistic regression models evaluated predictors of CDI likelihood, and of CDI remaining sustained at 5 years. Propensity-score-matched comparisons evaluated the effect of CDI on expanded disability status scale (EDSS) change at 5 years, risk of confirmed sustained EDSS⩾6, and secondary progressive MS (SPMS)-free survival.
Results: In 71,073 patients, 10,441 CDI events occurred. Medium and high-efficacy DMT use was associated with higher CDI likelihood (OR: 1.7, 95%CI=1.6-1.9; 2.9, 95%CI=2.7-3.2 respectively). CDIs occurring on high-efficacy DMTs, in younger patients and early in disease were more likely to remain sustained at 5-years. EDSS gain over 5-years was 1.5 steps lower (95%CI=1.5-1.6) following CDI. Risk of sustained EDSS⩾6 (HR: 0.30, 95%CI=0.26-0.35) and SPMS (HR: 0.67, 95%CI=0.62-0.73) was lower following CDI.
Conclusion: CDI events are more frequent following higher-efficacy DMT initiation. Patients experiencing CDI have more favourable medium and long-term disability outcomes, including lower risk of SPMS and needing mobility support. CDI is a clinically relevant and informative outcome for use in studies and potential treatment target.