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).

Keywords: Gastrointestinal events; Multiple sclerosis; Retrospective study; Tecfidera.

Figures

Fig. 1

Incidence of gastrointestinal (GI) adverse events (AEs) over time. The numbers above bars are the proportion (in percentage) of patients with GI AEs. DMF Delayed-release dimethyl fumarate

Fig. 2

Most commonly recommended types of foods (a) and classes of medication(s) (b) for GI event mitigation. Sites were instructed to select all that applied. n Number of sites (total number of sites 65). aOther classification included antacid medications (e.g., calcium carbonate) (n = 22); histamine 2 blocker (n = 1), and nonsteroidal anti-inflammatory drugs (n = 1)

Fig. 3

Counseling practices regarding GI event associated with DMF treatment, reported by sites. Very likely indicates counseling for > 75% of the time. Not all sites responded to all questions [n = 63 for counseled; n = 64 for counseled by another healthcare provider (HCP) in addition to the prescriber; n = 63 for counseled by another HCP, in lieu of the prescriber]. aAnother HCP in addition to the prescriber could include a registered nurse, physician, nurse practitioner, physician assistant, or pharmacist. bHCP in lieu of the prescriber could include a registered nurse, physician, nurse practitioner, physician assistant, or pharmacist

Fig. 4

Proportion of patients who discontinued DMF by site frequency of GI management strategy implementation. Specific details of GI event included information on timing of onset, incidence, severity, and duration. Nonoral counseling materials included handwritten, printed, emailed, online, or other information. Sites could select more than one option. Not all sites responded to all questions; sites may have been in the very likely and/or not very likely category for each of the mitigation strategies depending on their response in the questionnaire. Very likely, > 75% of the time; not very likely, 0–75% of the time. Number of discontinuations/number of patients who received the management strategy described is shown in the figure (proportions are indicated along the X-axis)