Real-World Characterization of Dimethyl Fumarate-Related Gastrointestinal Events in Multiple Sclerosis: Management Strategies to Improve Persistence on Treatment and Patient Outcomes

Abstract

Introduction Delayed-release dimethyl fumarate (DMF) is an effective treatment for multiple sclerosis (MS). Some patients experience gastrointestinal (GI) adverse events (AEs) that may lead to premature DMF discontinuation. This study characterized the impact of site-specific GI management strategies on the occurrence of GI events and discontinuation patterns. Methods Data on GI events and DMF persistence were retrospectively abstracted from medical records of patients treated with DMF in routine medical practice in the EFFECT study (NCT02776072). GI management strategies were assessed via a study site questionnaire. Discontinuation rates were analyzed according to counseling patterns. Results Of 826 DMF-treated patients at 66 sites, 809 from 65 sites were eligible for the GI analysis; of these, 27% experienced GI AEs. Within 1 year of treatment, 14% (118/826) of patients discontinued DMF, 5% (44/809) due to GI events. Most sites (92%) reported that patients were very likely (> 75% of the time) to be counseled about GI events at/before DMF treatment initiation and/or to be recommended that DMF be taken with food (86%); 48% of sites reported to be very likely to recommend using symptomatic therapies for GI AEs. Lower discontinuation rates were reported at sites very likely versus not very likely (≤ 75% of the time) to (1) provide counseling; (2) provide specific details regarding GI events; or (3) recommend taking DMF with food, and/or using symptomatic GI therapies. Conclusion Counseling and other GI management strategies at initiation of DMF treatment appear to reduce the burden of GI events, and a variety of GI management strategies may improve DMF persistence. Trial Registration NCT02776072. Funding Biogen (Cambridge, MA, USA). Electronic supplementary material The online version of this article (10.1007/s40120-019-0127-2) contains supplementary material, which is available to authorized users.

Delayed-Release Dimethyl Fumarate Safety and Efficacy in Pediatric Patients With Relapsing-Remitting Multiple Sclerosis

“…Overall, 91% of participants in FOCUS experienced an AE; six SAEs were reported in five participants, none related to DMF treatment (25). Gastrointestinal-related AEs were lower in CONNECTED than FOCUS (31), as would be expected because the majority of gastrointestinal-related AEs occur in adults in the first 5 weeks of DMF treatment (37).…”

SwissTecLive: effectiveness and safety of dimethyl fumarate in the treatment of RRMS in the Swiss clinical practice setting

“…Several retrospective studies and some in real-world settings concur on the importance of counseling for DMF tolerability and GI management to enhance treatment adherence and prevent therapy discontinuation ( Begus-Nahrmann et al., 2015 , 2016 ; Min et al., 2019 ; Niemczyk et al., 2018 ; Phillips et al., 2016 ). Patients referred more to the support program after the experience of an adverse event.…”

Diroximel Fumarate Demonstrates an Improved Gastrointestinal Tolerability Profile Compared with Dimethyl Fumarate in Patients with Relapsing–Remitting Multiple Sclerosis: Results from the Randomized, Double-Blind, Phase III EVOLVE-MS-2 Study

“…In a real-world study, up to 88% of patients treated with DMF reported GI events when self-assessing GI symptoms using eDiaries [9]. Although GI symptom management and mitigation approaches have been developed, DMF treatment discontinuation because of GI AEs still occurs and varies between 5 and 19% in realworld studies [11,12].…”