Safety and Efficacy of Delayed-release Dimethyl Fumarate in Multiple Sclerosis Patients Treated in Routine Medical Practice: Interim Analysis of ESTEEM (P6.333)

Objective: Report 1-year, safety and efficacy results in patients with relapsing-remitting multiple sclerosis (RRMS) treated with delayed-release dimethyl fumarate (DMF) under routine care in ESTEEM (NCT02047097). Background: DMF demonstrated strong efficacy and a favorable benefit–risk profile in clinical studies of patients with RRMS. ESTEEM is an ongoing 5-year multinational prospective, non-interventional study. Design/Methods: Patients newly prescribed DMF under routine clinical care were recruited from ~380 sites. The primary objective was to determine the incidence, type, and pattern of serious adverse events (SAEs) and AEs leading to treatment discontinuation. Secondary objectives included measures of RRMS disease activity (annualized release rate, ARR) and patient-reported outcomes (PROs): the Multiple Sclerosis Impact Score, 5-dimension QOL, visual analog scale of overall health, Modified Fatigue Impact Scale-5, and Work Productivity and Activity Impairment-MS. Results: As of April 12, 2016, 2025 patients had ≥1 dose of DMF and qualified for the analysis. Mean (SD) age was 41.3 (11.5) years; 75.4% were female. Seventy-three patients (3.6%) experienced SAEs, of which infections (0.9%) and gastrointestinal disorders (0.4%) were the most common. Of the 496 (24.5%) patients who discontinued treatment, 43 (2.1%) were due to lack of efficacy. A total of 315 patients (15.6%) reported AEs leading to treatment discontinuation; 144 (7.1%) discontinued due to gastrointestinal AEs. In all, 40 (2.0%) discontinued due to decreases in lymphocyte count/occurrence of lymphopenia. Of 1672 patients with ≥1 lymphocyte count, 15 (0.9%) had severe, prolonged lymphopenia ( 9 /L for ≥6 months). ARR at Year 1 (0.17; 95% CI 0.15, 0.19) was significantly lower than in the year prior to baseline (0.79, 95% CI 0.75, 0.82; P Conclusions: Interim results of safety and efficacy suggest that the overall benefit-risk of DMF in RRMS patients remains favorable in routine clinical practice. Study Supported by: Biogen Disclosure: Dr. Everage has received personal compensation for activities with Biogen Idec as an employee. Dr. Everage holds stock and/or stock options in Biogen Idec. Dr. Prada has received personal compensation for activities with Biogen as an employee. Dr. Prada holds stock and/or stock options in Biogen. Dr. Liu has received personal compensation for activities with Biogen as an employee. Dr. Balashov has received personal compensation for activities with Teva and Genzyme. Dr. Balashov has received research support from Biogen. Dr. Macdonell has received personal compensation for activities with Roche, Merck, Genzyme, and Novartis for serving on advisory boards. Dr. Windsheimer has received personal compensation for activities with Teva, Roche, Merck, Genzyme and Novartis as an advisory board member. Dr. Giles has received personal compensation for activities with EMD Serono as a consultant. Dr. Giles has received personal compensation for activities with Genzyme as an advisory board member. Dr. Giles has received personal compensation for activities with Biogen for services on speakers9 bureau and advisory board.