Background: Dimethyl fumarate (DMF) demonstrated strong efficacy and a favorable benefitrisk profile in patients with relapsing-remitting multiple sclerosis (RRMS) in clinical studies. ESTEEM (NCT02047097), is a multinational, 5-year, prospective, non-interventional study to evaluate the long-term safety and effectiveness of DMF in patients treated in clinical practice.
Objectives: To report 5-year safety and effectiveness in patients with MS treated with DMF under routine care in ESTEEM.
Methods: Patients prescribed DMF were recruited from ~380 sites. The primary objective was to determine incidence, type, pattern of serious adverse events (SAEs), and AEs leading to discontinuation. Secondary objectives include assessment of DMF effectiveness on annualized relapse rate (ARR) and patient-reported outcomes (PROs). Analyses included the overall population, newly diagnosed (no prior disease-modifying therapy [DMT] and initiated DMF ?1 year of diagnosis), early MS (?1 prior DMT and initiated DMF ?3 years of diagnosis), and IFN/GA switch (received prior IFN/GA at any time from diagnosis) patients.
Results: As of April 3, 2019, 5084 patients had ?1 dose of DMF and qualified for analysis. Mean (SD) age, 40.0 (11.2) years at enrollment, 74% were female. In total, 1506 patients were treated for ?2448 months, and 441 for ?48 months. Overall, 245 (4.8%) experienced SAEs; infections (n=64;1.3%) and nervous system disorders (n=35;<1%) were most common. A total of 965 patients (19.0%) discontinued DMF due to AEs; the majority due to gastrointestinal disorders (7.8%). Model-based ARRs (Poisson regression model for repeated measures) for 1 year before vs. 5 years post DMF were as follows: overall population (n=5084), 0.82 (95%confidence interval[CI]:0.800.84) vs. 0.09 (95%CI:0.090.10), 88.6% reduction in ARR (P<0.0001); newly diagnosed patients (n=1447), 1.12 (95%CI:1.081.16) vs. 0.10 (95%CI:0.090.11), 91.3% reduction in ARR (P<0.0001); early MS patients (n=2364), 1.03 (95%CI:1.001.06) vs. 0.10 (95%CI:0.090.11), 90.3% reduction in ARR (P<0.0001); and IFN/GA switch patients (n=2976), 0.69 (95%CI:0.660.72) vs. 0.09 (95%CI:0.080.10), 86.5% reduction in ARR (P<0.0001). The Kaplan-Meier estimated probability of patients without a relapse at 5 years in the overall population was 71.1%, and 75.8% in patients newly diagnosed. PROs were generally stable from baseline to 48 months across all patient subgroups. Conclusions: Results from the 5-year analysis reveal no new safety concerns emerging from the use of DMF in MS patients treated with DMF in the real-world setting. ARR at 5 years was significantly reduced vs. the year prior to DMF initiation. These data provide further evidence of real-world effectiveness of DMF in patients early in their MS disease course.