Diroximel fumarate (DRF) is a novel oral fumarate approved for relapsing forms of multiple sclerosis (MS) with the same active metabolite as dimethyl fumarate (DMF). DRF demonstrated improved gastrointestinal (GI) tolerability vs DMF, with significantly fewer days with a score of ≥2 on the patient-assessed Individual Gastrointestinal Symptom and Impact Scale (IGISIS).
To determine whether an IGISIS score ≥2 is an appropriate threshold for comparing GI tolerability and detecting clinically meaningful quality of life (QoL) improvements in EVOLVE-MS-2.
EVOLVE-MS-2 (NCT03093324) was a 5-week, randomized study comparing GI tolerability of DRF vs DMF in patients with relapsing-remitting MS. Patients self-assessed severity of 5 key GI symptoms by completing IGISIS and Global GISIS (GGISIS) questionnaires. GGISIS assessed interference of GI symptoms on daily activities and missed work. The association between worst IGISIS score ≥2 and measures of treatment burden (worst interference with daily activities, missed work due to GI symptoms, and use of concomitant symptomatic medication to treat GI AEs) by treatment group was assessed using risk ratios (RR; DRF/DMF).
Overall, 253 patients received DRF and 251 received DMF. Fewer DRF-treated patients reported any IGISIS score ≥2 (DRF, 43.1% [109/253]; DMF, 51.4% [128/249]). IGISIS score ≥2 detected moderate/severe GI AEs of IGISIS with 90% sensitivity and 59% specificity. Among patients reporting GI symptoms as “Quite a Bit” or “Extremely” interfering with daily activities (n=47) or missing ≥ 1 hour work due to GI symptoms (n=46) using GGISIS, 89.4% and 91.3% reported a worst IGISIS score ≥2, respectively. In patients with worst IGISIS score ≥2, DRF was associated with lower likelihood of GI symptoms interfering with daily activities “Quite a bit” or “Extremely” (RR 0.88; 95% CI 0.51–1.53), leading to missed work (RR 0.88; 95% CI 0.51–1.53), and resulting in concomitant symptomatic medication use for GI AEs (RR 0.57; 95% CI 0.32–1.00).
Fewer patients reported IGISIS score ≥2 with DRF vs DMF, and an IGISIS score ≥2 was sensitive for identifying moderate/severe GI AEs and clinically meaningful GI symptoms that could impact QoL from a patient perspective.
Supported by: Biogen