Long-Term Safety and Effectiveness of Delayed-release Dimethyl Fumarate in Multiple Sclerosis Patients Treated in Routine Medical Practice, an updated analysis of the ESTEEM Study
Krupa Pandey1, Kathryn Giles2, Konstantin Balashov3, Richard Macdonell4, Jorg Windsheimer5, Mikel Martinez6, Ivan Bozin7, Xiaotong Jiang7, Jennifer Lyons7, Oksana Mokliatchouk7, Annette Okai8
1Hackensack University Medical Center, 2Cambridge Memorial Hospital, 3Boston Medical Center, 4Austin Health, Univ. of Melbourne, 5Praxis für Neurologie und Psychiatrie, 6Centre Hospitalier Dax, 7Biogen Inc., 8North Texas Institute of Neurology and Headache
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.