Dimethyl fumarate (DMF) has demonstrated a favorable benefit–risk profile in patients with relapsing–remitting multiple sclerosis (RRMS) in clinical and real-world studies. The ESTEEM study (NCT02047097) was conducted to assess the long-term safety and effectiveness of delayed-release DMF in patients with relapsing forms of MS in routine clinical practice. We report final outcomes from ESTEEM with up to 6.5 years of follow-up. Patients newly prescribed DMF were recruited from 393 sites globally. The primary objective was to assess the incidence and type of serious adverse events (SAEs) and adverse events (AEs) leading to discontinuation of DMF. Secondary objectives included assessment of DMF effectiveness on annualized relapse rate (ARR) and patient-reported outcomes (PROs). Overall, 5124 patients received ≥ 1 dose of DMF. The mean (standard deviation [SD]) age at enrollment was 40.0 (11.2) years; 74

Objective: To assess long-term safety and effectiveness of delayed-release dimethyl fumarate (DMF) in patients with relapsing forms of multiple sclerosis (MS) in clinical practice. Background: DMF has demonstrated a favorable benefit–risk profile in patients with relapsing forms of MS in clinical trials and real-world studies. To provide information on long-term exposure in clinical practice, the ESTEEM study (NCT02047097) was conducted. Design/Methods: 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). Results: As of April 2021, 5251 patients had received >1 dose of DMF. Mean (SD) age of patients at enrollment was 40.1 (11.2) years; 74.0% were female. Patients received DMF for a mean (SD) duration of 30.4 (20.4) months. Primary reasons for discontinuation were AEs (1066/5251; 20.3%), of which the most common were gastrointestinal AEs (442/1066; 41.5%), and efficacy reasons (439/5251, 8.4%). Of 5251 patients, 173 (3.3%) patients discontinued due to lymphopenia. SAEs were reported in 326 (6.2%) patients, most commonly infections and infestations (n=86; 1.6%). No PML was reported. Adjusted ARR (95% CI) remained low, ranging from 0.16 (0.14–0.17) after Year 1 to 0.05 (0.04–0.08) 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 5.5 years compared with baseline. Conclusions: In this interim analysis, DMF demonstrated a safety profile in real-world clinical practice consistent with the known profile of DMF. Similarly, relapse rates were low and both ARR and PROs remained stable over time. This indicates a sustained effectiveness for patients who remain on DMF treatment for up to 5 years. Disclosure: Dr. Pandey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Pandey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi Genzyme. Dr. Pandey has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech . Dr. Pandey has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for BMS. Dr. Pandey has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Biogen . Dr. Pandey has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Pandey has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genentech . Dr. Pandey has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Horizon Therapeutics . The institution of Dr. Pandey has received research support from NIH. The institution of Dr. Pandey has received research support from CMSC. Kathryn Giles has stock in Synderdisc. The institution of Kathryn Giles has received research support from Biogen. Dr. Balashov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Macdonell has nothing to disclose. Jorg Windsheimer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck, Biogen,BMS,Janssen,Roche,Hexal. Jorg Windsheimer has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen,Teva,BMS. Mikel Martinez has nothing to disclose. Dr. Bozin has received personal compensation for serving as an employee of Biogen. Dr. Bozin has received personal compensation for serving as an employee of Arvelle Therapeutics. Dr. Bozin has stock in Biogen. Xiaotong Jiang has nothing to disclose. Dr. Lyons has received personal compensation for serving as an employee of Biogen. Dr. Lyons has received stock or an ownership interest from Biogen. Oksana Mokliatchouk has received personal compensation for serving as an employee of Biogen. Oksana Mokliatchouk has received stock or an ownership interest from Biogen. Dr. Okai has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Okai has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Okai has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Okai has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Okai has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Okai has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Okai has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi Genzyme. Dr. Okai has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Okai has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Okai has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for EMD SERONO . Dr. Okai has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi Genzyme .

Monday, April 27April 14, 2020Free AccessSafety and Effectiveness of Dimethyl Fumarate Maintained Over 4 Years in Multiple Sclerosis Patients Treated in Routine Medical Practice (1346)Krupa Pandey, Kathryn Giles, Konstantin Balashov, Richard Macdonell, Jörg Windsheimer, Oksana Mokliatchouk, Becky Parks, Filipe Branco, and Cynthia C. JonesAuthors Info & AffiliationsApril 14, 2020 issue94 (15_supplement)https://doi.org/10.1212/WNL.94.15_supplement.1346 Letters to the Editor

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.