Delayed-Release Dimethyl Fumarate As Add-on Therapy to Beta Interferon or Glatiramer Acetate in Relapsing-Remitting MS: Safety and Tolerability

Background: Delayed-release dimethyl fumarate (DMF) demonstrated significant efficacy and an acceptable safety profile in patients with relapsing-remitting multiple sclerosis (RRMS) in placebo-controlled clinical trials.

Objectives: To describe the safety and tolerability of delayed-release DMF as add-on therapy to beta-interferons (IFNβ) or glatiramer acetate (GA) in the Phase 2, open-label EXPLORE study.

Methods: Eligibility criteria included age 18–55 years, RRMS diagnosis (McDonald criteria), EDSS score 0–5.0, established therapy with the same dose of IFNβ or GA for ≥12 months, and ≥1 relapse within 12 months or gadolinium-enhancing lesion(s) on MRI within 6 weeks prior to enrolment. Patients continued on their prescribed MS therapy for 2 months (monotherapy period), then received delayed-release DMF 240mg three times daily (TID) in addition to their prescribed MS therapy for 6 months (add-on therapy period).

Results: During the add-on therapy period, in the delayed-release DMF/INFβ (n=57) and delayed-release DMF/GA (n=47) groups, the overall incidence of AEs was 95% and 100%; the most common AEs were flushing (42% and 53%), diarrhea (32% and 15%), and abdominal pain (21% and 6%). Most AEs were reported as mild or moderate in severity. There was no overall increased risk of infection. No malignancies were reported. At Week 24, mean percentage decrease of lymphocyte counts from baseline was 22% (delayed-release DMF/IFNβ) and 7% (delayed-release DMF/GA). There was a transient increase in liver transaminases; no case fulfilled Hy’s law. There were no deaths.

Conclusions: The safety profile of delayed-release DMF in combination with IFNβ or GA was similar to the known safety profile of delayed-release DMF monotherapy. There were no unexpected safety signals.