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Diroximel Fumarate Demonstrates an Improved Gastrointestinal Tolerability Profile Compared with Dimethyl Fumarate in Patients with Relapsing–Remitting Multiple Sclerosis: Results from the Randomized, Double-Blind, Phase III EVOLVE-MS-2 Study
- Source :
- CNS Drugs
- Publication Year :
- 2020
- Publisher :
- Springer International Publishing, 2020.
-
Abstract
- Background Diroximel fumarate (DRF) is a novel oral fumarate approved in the USA for relapsing forms of multiple sclerosis. DRF is converted to monomethyl fumarate, the pharmacologically active metabolite of dimethyl fumarate (DMF). DRF 462 mg and DMF 240 mg produce bioequivalent exposure of monomethyl fumarate and are therefore expected to have similar efficacy/safety profiles; the distinct chemical structure of DRF may contribute to its tolerability profile. Objectives The objective of this study was to compare the gastrointestinal tolerability of DRF and DMF over 5 weeks in patients with relapsing–remitting multiple sclerosis. Methods EVOLVE-MS-2 was a phase III, randomized, double-blind, head-to-head, 5-week study evaluating the gastrointestinal tolerability of DRF 462 mg vs DMF 240 mg, administered twice daily in patients with relapsing–remitting multiple sclerosis, using two self-administered gastrointestinal symptom scales: Individual Gastrointestinal Symptom and Impact Scale (IGISIS) and Global Gastrointestinal Symptom and Impact Scale (GGISIS). The primary endpoint was the number of days with an IGISIS intensity score ≥ 2 relative to exposure. Other endpoints included the degree of gastrointestinal symptom severity measured by IGISIS/GGISIS and assessment of safety/tolerability. Results DRF-treated patients experienced a statistically significant reduction (46%) in the number of days with an IGISIS symptom intensity score ≥ 2 compared with DMF-treated patients (rate ratio [95% confidence interval]: 0.54 [0.39–0.75]; p = 0.0003). Lower rates of gastrointestinal adverse events (including diarrhea, nausea, vomiting, and abdominal pain) were observed with DRF than DMF (34.8% vs 49.0%). Fewer patients discontinued DRF than DMF because of adverse events (1.6% vs 5.6%) and gastrointestinal adverse events (0.8% vs 4.8%). Conclusions DRF demonstrated an improved gastrointestinal tolerability profile compared with DMF, with less severe gastrointestinal events and fewer days of self-assessed gastrointestinal symptoms, fewer gastrointestinal adverse events, and lower discontinuation rates because of gastrointestinal adverse events. Clinical Trials Registration ClinicalTrials.gov (NCT03093324). Electronic supplementary material The online version of this article (10.1007/s40263-020-00700-0) contains supplementary material, which is available to authorized users.
- Subjects :
- Adult
Male
medicine.medical_specialty
Abdominal pain
Nausea
Gastrointestinal Diseases
Dimethyl Fumarate
Gastroenterology
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Multiple Sclerosis, Relapsing-Remitting
Double-Blind Method
Fumarates
Recurrence
Internal medicine
medicine
Clinical endpoint
Humans
Pharmacology (medical)
Original Research Article
Adverse effect
Dimethyl fumarate
business.industry
030227 psychiatry
Discontinuation
Gastrointestinal Tract
Psychiatry and Mental health
chemistry
Tolerability
Vomiting
Female
Neurology (clinical)
medicine.symptom
business
030217 neurology & neurosurgery
Immunosuppressive Agents
Subjects
Details
- Language :
- English
- ISSN :
- 11791934 and 11727047
- Volume :
- 34
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- CNS Drugs
- Accession number :
- edsair.doi.dedup.....ca8913e2f749d7400243f5d2ebf08015