To assess the 6-year safety and effectiveness of delayed-release dimethyl fumarate (DMF) treatment of patients with relapsing multiple sclerosis (MS) in clinical practice.

In clinical studies, DMF demonstrated a favorable benefit–risk profile in patients with relapsing-remitting MS. To further characterize risks that may emerge with long-term exposure in clinical practice, the ESTEEM study (NCT02047097) was conducted.

In this ongoing study, patients treated with DMF were recruited from ~380 sites. The primary objective was to assess the incidence and type of serious adverse events (SAEs), and AEs leading to discontinuation. Secondary objectives included assessment of DMF effectiveness on annualized relapse rate (ARR) and patient-reported outcomes (PROs).

As of April 2020, 5090 patients had received >1 dose of DMF. Mean (SD) age of patients was 40 (11) years at enrollment; 74% were female. Patients received DMF for a mean (SD) duration of 27.1 (18.8) months. Over 6 years, AE was the primary reason for discontinuations in 1102 (21.7%) patients, most commonly gastrointestinal disorders (425 [8.3% of 5090) followed by 383 patients (18%) who discontinued DMF primarily for efficacy reasons. 

Serious AEs were reported in 304 (6.0%) patients; most commonly infections and infestations (n=76; 1.5%). Adjusted ARR (95% CI) remained low and consistent over 6 years of DMF treatment, ranging from 0.16 (0.14, 0.17) after Year 1 to 0.04 (0.02, 0.08) after Year 5. Mean scores for measures of physical and psychological impact, fatigue, overall health outcomes, and work productivity and activity impairment remained stable at 48 months compared with baseline.

Results from the 6-year interim analysis demonstrate the safety profile in this ongoing, real-world observational study is consistent with the known profile of DMF. Similarly, relapse rates were low and both ARR and PROs remained stable over time indicating sustained effectiveness for patients who remain on DMF treatment over 6 years.

Support:Biogen