Matching-adjusted indirect treatment comparison of ozanimod versus teriflunomide for relapsing multiple sclerosis

Abstract

Background: A growing number of immunomodulating disease-modifying therapies are available for treatment of relapsing multiple sclerosis (RMS). In the absence of randomized head-to-head trials, matching-adjusted indirect comparisons (MAICs) can be used to adjust for cross-trial differences and evaluate the comparative efficacy and safety of these agents. We used MAIC methodology to indirectly compare key outcomes with ozanimod (OZM) and teriflunomide (TERI) in the treatment of RMS.

Methods: A systematic literature review was conducted to identify clinical trials evaluating the efficacy and safety of OZM vs TERI. Given the absence of head-to-head trials of OZM vs TERI, we used a matching-adjusted indirect comparison to adjust for potential treatment effect modifiers and prognostic factors while assessing confirmed disability progression (CDP), relapse, and safety outcomes. Individual patient data for OZM (SUNBEAM and RADIANCE Part B trials) and aggregate level data for TERI (ASCLEPIOS I/II, TOWER, OPTIMUM, and TEMSO trials) were used to evaluate the following outcomes: annualized relapse rate (ARR), proportion of patients relapsed, CDP at 3 and 6 months, overall adverse events (AEs), serious AEs (SAEs), and discontinuations due to AEs.

Results: After matching, baseline patient characteristics were balanced between OZM and TERI. Compared with TERI, OZM demonstrated significant improvements in ARR (rate ratio: 0.73; 95% CI: 0.62-0.84), proportion of patients relapsed (odds ratio [OR]: 0.56; 95% CI: 0.44-0.70), overall AEs (OR: 0.35; 95% CI: 0.29-0.43), SAEs (OR: 0.53; 95% CI: 0.37-0.77), and discontinuations due to AEs (OR: 0.14; 95% CI: 0.09-0.21). OZM demonstrated statistically significant improvements in CDP at 3 months (hazard ratio [HR]: 0.78; 95% CI: 0.66-0.92) but nonsignificant differences at 6 months (HR: 0.78; 95% CI: 0.60-1.01) compared with TERI.

Conclusion: In this indirect treatment comparison of patients with RMS, OZM appeared to have an improved benefit-risk profile over TERI.

Keywords: Annualized relapse rate; Confirmed disability progression; Disease-modifying therapy; Individual patient data; Safety.