Why carry out this study?

Diroximel fumarate (DRF) previously demonstrated improved gastrointestinal (GI) tolerability compared with dimethyl fumarate (DMF) in the phase 3, randomized, head-to-head double-blind EVOLVE-MS-2 trial of patients with relapsing–remitting multiple sclerosis (RRMS).

An interim analysis of the ongoing, open-label, 96-week, phase 3 EVOLVE-MS-1 study of adults with RRMS indicated a low incidence of GI adverse events (AEs) and a very low rate of treatment discontinuation due to GI AEs in the overall study population, but an analysis of DRF outcomes following prior disease-modifying therapy (DMT) has not been conducted.

The objectives of this analysis were to (1) assess safety and efficacy outcomes in patients with RRMS and up to 2 years of DRF treatment who had received prior glatiramer acetate (GA) or interferon (IFN) as their most recent DMT before initiating DRF in EVOLVE-MS-1, and (2) evaluate GI tolerability in patients who completed 5 weeks of DRF or DMF treatment in EVOLVE-MS-2 before initiating DRF in EVOLVE-MS-1.

What was learned from the study?

Safety outcomes in patients who switch to DRF treatment were consistent with what has been reported for the overall population: AEs were generally mild or moderate in severity and led to treatment discontinuation at an overall similar rate among all analysis groups; absolute lymphocyte count decreased by approx. 30% over the first year of treatment with DRF and then stabilized to a level greater than the lower limit of normal for the majority of patients consistent with other DMF studies.

Patients treated with DRF over 2 years experienced improvements on clinical and radiological efficacy relative to those reported for the preceding treatment period with IFN and GA. Adjusted annualized relapse rate was significantly reduced (p < 0.0001 for both prior IFN and prior GA groups) after up to 2 years of DRF treatment compared with the reported annualized relapse rate in the 12 months before fumarate initiation.

Patients with prior DMF or DRF treatment for 5 weeks in EVOLVE-MS-2 had low rates of new or recurring GI AEs after initiating DRF in the 2-year EVOLVE-MS-1 study, and the rate of treatment discontinuation due to GI AEs across both groups (prior DMF or prior DRF) was < 1%. The data suggest that transition from DMF to DRF, which have the same active metabolite, is a reasonable treatment strategy for appropriate patients with RRMS.