Safety and Effectiveness of Delayed-Release Dimethyl Fumarate in a Canadian Cohort Enrolled in the ESTEEM Study

Background: ESTEEM is an ongoing, multinational, prospective, 5-year observational study evaluating the long-term safety and efficacy of delayed-release dimethyl fumarate (DMF) in patients with relapsing multiple sclerosis (RMS) newly treated with DMF under routine clinical care. Primary endpoints included the incidence, type, and patterns of treatment-emergent severe adverse events (SAEs) and AEs leading to treatment discontinuation. As of 12 April 2016, 2025 patients were enrolled and dosed. Interim results presented here will inform Canadian healthcare professionals and DMF patient care.

Objectives: To describe the Canadian cohort included in the ESTEEM study and to report interim safety and efficacy results from this subgroup.

Methods: All Canadian patients who received at least 1 dose of DMF were included. Annualized relapse rate (ARR) and reduction in ARR were estimated using a repeated measures, mixed negative binomial model. The proportion of patients with relapses at 6 and 12 months, and Kaplan-Meier (KM) estimates of time to first relapse, were used to evaluate the risk of relapse.

Results: Of the 130 Canadian patients enrolled, 121 were analyzed (undosed patients were excluded); 87 (72%) were female, and the median age was 40 years. The majority of patients (79 [65%]), received one or more prior MS treatments (23% - intramuscular interferon [IFN] beta-1a, 47% - subcutaneous IFN beta-1a, 33% - glatiramer acetate; not mutually exclusive).

At one year after DMF initiation, unadjusted ARR was 0.16 vs 0.74 within 12 months before DMF initiation, representing a 78% (95%CI=62, 87%) lower ARR after DMF initiation (p<0.0001). KM analysis showed that the proportion of relapse-free patients was 92% and 85% at 6 and 12 months, respectively.

Serious AEs were reported in 4 (3%) patients; no confirmed opportunistic infections were attributed to DMF. Two deaths, considered unrelated to DMF treatment, occurred during the study. AEs leading to treatment discontinuation in 1% or more of the population included: gastrointestinal disorders (11%), blood/lymphatic system disorders (4%), nervous system disorders (4%), vascular disorders (3%), infections/infestations (3%), and skin/subcutaneous tissue disorders (3%).

Conclusions: ARR after one year of DMF was significantly lower than in the year prior to DMF initiation. AEs were consistent with the known safety profile of DMF and observations made in the Canadian cohort were consistent with the overall ESTEEM population.