To evaluate tolerability and impact of gastrointestinal (GI) adverse events (AEs) with diroximel fumarate (DRF) versus dimethyl fumarate (DMF) in patients with relapsing-remitting multiple sclerosis (MS).

DRF is an investigational, oral fumarate for relapsing forms of MS with an improved GI tolerability profile compared to DMF. DRF 462 mg and DMF 240 mg produce bioequivalent exposure of the active metabolite monomethyl fumarate. Well-tolerated treatment options may lower treatment burden for patients.

EVOLVE-MS-2 (NCT03093324) is a randomized, double-blind study evaluating GI tolerability of twice-daily DRF 462 mg and DMF 240 mg. Patient-assessed GI symptoms were evaluated using two scales: Individual Gastrointestinal Symptom and Impact Scale (IGISIS) and Global Gastrointestinal Symptom and Impact Scale (GGISIS). Interference and burden of GI symptoms were explored.

Among patients with ≥1 post-baseline self-assessment of GI tolerability (n=502), fewer DRF- versus DMF-treated patients characterized their GI events as interfering with regular daily activities “quite a bit” and “extremely”: nausea (2.4% vs 6.8%), vomiting (1.2% vs 5.6%), upper abdominal pain (1.2% vs 6.8%), lower abdominal pain (1.2% vs 3.2%), and diarrhea (3.6% vs 6.4%). DRF- compared to DMF-treated patients were less likely to have an IGISIS score ≥2 for ≥2 consecutive days (17.4% vs 29.3%; risk ratio 0.59 [95% CI, 0.43-0.83]). Fewer DRF-treated patients reported concomitant medications for GI tolerability (17/88 [19.3%]) compared to DMF (37/121 [30.6%]). Among patients receiving ≥1 dose of study drug (n=504), GI AEs were lower with DRF than DMF (88/253 [34.8%] vs 123/251 [49.0%]).Treatment discontinuation due to GI AEs was lower for DRF versus DMF (0.8% vs 4.8%).

GI symptoms interfered less with daily activities for DRF-treated patients compared to DMF. Further benefits on additional measures of treatment burden, including lower medication use for GI symptoms, were seen with DRF. GI AEs leading to discontinuation were <1% for DRF-treated patients.