Dimethyl Fumarate

Abstract

Background: Delayed-release dimethyl fumarate (DMF; also known as gastroresistant DMF) is indicated for the treatment of relapsing multiple sclerosis. Flushing and gastrointestinal (GI) adverse events (AEs) are common within the first few months of starting DMF therapy. Although most symptoms are mild or moderate in severity, transient, and infrequently result in treatment discontinuation, they nevertheless present a challenge for patients to adhere to therapy and achieve an optimal treatment response. Methods: This review discusses management strategies for the prophylaxis and treatment of common DMF-associated AEs based on clinical trial evidence and real-world experience in clinical practice settings. Results: Before starting DMF therapy, patients should receive counseling on the importance of treatment adherence and the likely occurrence and severity of flushing and GI AEs (nausea, vomiting, diarrhea, and abdominal pain). Management strategies, such as administering DMF with food, using a slower-dose titration schedule, applying temporary dose reductions, and using symptomatic therapies, provide clinicians with several approaches to address DMF tolerability. In particular, DMF coadministration with certain foods (eg, sausage, peanut butter) may prevent or reduce the severity of GI AEs. Taking aspirin 325 mg/day 30 minutes before administering DMF in the first month of therapy can reduce the incidence and severity of flushing without negatively affecting GI-related events. Conclusions: Through continual patient education and support and management of treatment-related flushing and GI AEs, clinicians can help patients adhere to and persist with DMF therapy, thus maximizing treatment benefit.

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

“…The incidence of GI AEs (27%) and the proportion of patients discontinuing treatment as a result of GI AEs (5%) in our analysis was somewhat lower than has been reported in other real-world studies, but similar to what was observed in controlled clinical trials [4, 6, 11]. The data from the site survey responses indicate a high likelihood that the patients in this study were counseled about GI symptoms associated with DMF treatment.…”

“…Thus, it is important that counseling patients regarding potential GI AEs occurs at or before treatment initiation [4, 6–10]. Although most treatment-emergent GI AEs are generally mild or moderate in nature [11], these events may lead to poor treatment compliance or premature DMF discontinuation for some patients.…”

Diroximel fumarate (DRF) in patients with relapsing–remitting multiple sclerosis: Interim safety and efficacy results from the phase 3 EVOLVE-MS-1 study

“…GI events, typically occurring within 1-2 months of treatment initiation, are among the most commonly reported AEs in clinical and real-world studies of DMF and have led to DMF treatment discontinuation in up to 20% of patients. 2,3,[11][12][13][14][15][16] In EVOLVE-MS-1, DRF appeared to be associated with lower than expected rates of GI and serious GI events based on studies with other fumaric acid esters. 1,17 In DRFtreated patients with GI AEs, events typically occurred within the first month of treatment and were short, lasting 7.5 days for most patients.…”

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.…”