Comparative Effectiveness of Diroximel Fumarate vs. Dimethyl Fumarate in Persons with Multiple Sclerosis: A US Claims Analysis of Relapse Outcomes.

INTRODUCTION: Diroximel fumarate (DRF) and dimethyl fumarate (DMF) are established disease-modifying therapies for relapsing multiple sclerosis (RMS). While DRF has demonstrated improved gastrointestinal tolerability compared to DMF, there is limited research evaluating whether this difference in tolerability translates into a difference in clinical effectiveness. This study evaluated the real-world effectiveness of DRF versus DMF on relapse outcomes in persons with MS (pwMS) in a large US population. METHODS: This retrospective cohort study utilized the Forian administrative claims database (January 1, 2018-June 30, 2025). Adult pwMS initiating DRF or DMF were identified and propensity score-matched (1:3 ratio) based on baseline demographic and clinical characteristics. Endpoints were assessed over 1- and 2-year follow-up periods. The primary endpoint was annualized relapse rate (ARR). RESULTS: The 1-year analysis included 1780 DRF-treated and 5340 DMF-treated pwMS; the 2-year analysis included 739 DRF-treated and 2217 DMF-treated pwMS. At 1 year of treatment, DRF was associated with a significantly lower ARR compared to DMF (0.12 vs. 0.16; p = 0.03), representing a 21% reduction in relapse rate (rate ratio 0.79; 95% CI 0.64-0.97). At 2 years of treatment, DRF maintained a lower ARR compared to DMF (0.11 vs. 0.16; p = 0.02), reflecting a 31% reduction in relapse rate (rate ratio 0.69; 95% CI 0.54-0.87). CONCLUSION: The results of this real-world analysis indicate DRF may be more effective than DMF in reducing relapses over 1 and 2 years of treatment in pwMS.