Abstract | BACKGROUND: OBJECTIVES: 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).
|
Authors | Robert T Naismith, Annette Wundes, Tjalf Ziemssen, Elzbieta Jasinska, Mark S Freedman, Anthony J Lembo, Krzysztof Selmaj, Ilda Bidollari, Hailu Chen, Jerome Hanna, Richard Leigh-Pemberton, Maria Lopez-Bresnahan, Jennifer Lyons, Catherine Miller, David Rezendes, Jerry S Wolinsky, EVOLVE-MS-2 Study Group |
Journal | CNS drugs
(CNS Drugs)
Vol. 34
Issue 2
Pg. 185-196
(02 2020)
ISSN: 1179-1934 [Electronic] New Zealand |
PMID | 31953790
(Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)
|
Chemical References |
- Fumarates
- Immunosuppressive Agents
- Dimethyl Fumarate
|
Topics |
- Adult
- Dimethyl Fumarate
(therapeutic use)
- Double-Blind Method
- Female
- Fumarates
(therapeutic use)
- Gastrointestinal Diseases
(drug therapy)
- Gastrointestinal Tract
(drug effects)
- Humans
- Immunosuppressive Agents
(therapeutic use)
- Male
- Multiple Sclerosis, Relapsing-Remitting
(drug therapy)
- Recurrence
|