Safety and efficacy of dimethyl fumarate: 13 years of follow-up

The overall benefit-risk ratio of dimethyl fumarate (DMF) remained favourable during a 13-year follow-up period [1]. Low rates of relapse were sustained throughout the 10-year treatment period. Rates of confirmed disability progression, serious infections, and malignancies were also low.

The final safety and efficacy results of DMF 240 mg twice daily (the approved dosage) were reported in patients with relapsing-remitting MS who were followed for 13 years in the ENDORSE trial (2 years DEFINE/CONFIRM and >10 years in ENDORSE). Patients were either treated with placebo in year 0-2 followed by DMF in year 3-10 (PBO/DMF) or with DMF continuously (DMF/DMF). Overall, 1,736 patients were enrolled in ENDORSE and 750 completed the study, 501 of whom received DMF/DMF and 249 PBO/DMF.

Annualised relapse rate (ARR) remained low throughout the study (see Figure). In the DMF/DMF group, ARR was 0.20 in year 1 and 0.11 in years 9-10. In the PBO/DMF group, ARR was 0.33 during placebo and 0.15 during DMF treatment. In the DMF/DMF and PBO/DMF group treated for up to 10 years, 45% and 42% of patients remained relapse-free, respectively, indicating that earlier treatment yields more favourable results. The percentage of patients with EDSS ≤3.5 over 10 years in the DMF/DMF group was 86% and 77% after 2 and 10 years, respectively; and 82% and 74% in the PBO/DMF group. In the DMF/DMF and PBO/DMF group, respectively, 72% and 73% of patients had no 24-week confirmed disability progression over 10 years.

Figure: Adjusted ARR by yearly interval in patients continuously treated with DMF or who switched from placebo after 2 years [1]



Overall, 551 (32%) patients experienced serious adverse events (AEs); most were MS relapse and falling. One case of progressive multifocal leukoencephalopathy was reported; there was no increased incidence of other infections or serious infections. AEs caused 16% of patients (n=282) to discontinue treatment, most commonly due to gastrointestinal and nervous system disorders. Absolute lymphocyte count decreased over the first 48 weeks, and then generally remained stable. The proportion of patients with other AEs of special interest (including opportunistic infection, malignancy, and serious herpes zoster) was similar regardless of absolute lymphocyte count. The authors concluded that these data further support DMF as a long-term option for patients with relapsing forms of MS.

1. Gold R, et al. Safety and Efficacy in Patients Treated With Dimethyl Fumarate and Followed For 13 Years: Final Results of ENDORSE. MSVirtual 2020, Abstract FC02.05.

 



Posted on 25 November, 2020