Use of a Delphi Process to Gain Consensus on Effective Management of Gastrointestinal Side Effects Associated with Delayed-Release Dimethyl Fumarate

Background:  Delayed-release dimethyl fumarate (DMF; also known as gastro-resistant DMF) 240 mg twice daily is approved for patients with relapsing-remitting multiple sclerosis (MS). Gastrointestinal (GI) side effects, especially in the first month of therapy, are an acknowledged accompaniment in some patients treated with DMF.

Objectives:  To use a Delphi consensus-building method to reach consensus on effective real-world management of GI events in patients receiving DMF.

Methods:  Clinicians in the US and Canada treating MS patients with DMF were asked to complete two rounds of questionnaires developed by the steering committee. Information from the first questionnaire was used to develop the second, which sought further clarification to achieve consensus (≥70% agreement) on management strategies for each type of GI event. Questions focused on the incidence and management of nausea, vomiting, abdominal pain and diarrhea. Values reported represent the percentage of respondents who agreed with the specified management strategy.

Results:  The first questionnaire was completed by 64 respondents and 57 completed the second; the majority (63/64 and 56/57, respectively) stated that ≥1 of their patients had experienced a GI side effect with DMF. Consensus was reached on taking DMF with food as a useful management strategy to reduce the incidence and/or severity of nausea (98%), vomiting (89%) and abdominal pain (93%). Respondents also agreed that slower DMF dose titration (>7 days to reach the approved maintenance dose) can be effective for reducing the incidence and/or severity of nausea (98%), vomiting (96%), abdominal pain (94%) and diarrhea (92%). Temporary DMF dose reduction was confirmed as a useful management strategy for reducing the impact of nausea (100%), vomiting (90%), abdominal pain (90%) and diarrhea (86%). Regarding specific medications, consensus was reached on using antacids (73%), bismuth subsalicylate (71%), ondansetron (93%) or promethazine (71%) for nausea; bismuth subsalicylate (71%), ondansetron (93%) or promethazine (71%) for vomiting; antacids (75%), bismuth subsalicylate (77%), H₂ blockers (73%) or proton pump inhibitors (80%) for abdominal pain; and diphenoxylate/atropine (91%) or loperamide (95%) for diarrhea.

Conclusions:  Clinicians with experience using DMF reached consensus on several potentially useful strategies to manage GI side effects, including administering DMF with food, slower titration, and use of symptomatic therapies.