BG-12 (Dimethyl Fumarate) Tolerability Delphi Panel

Background: In the BG-12 (dimethyl fumarate) Phase 3 clinical trials, common adverse events (AEs) associated with BG-12 included both flushing and gastrointestinal (GI) events. Most patients reported flushing and GI events that were mild/moderate in severity and decreased substantially in incidence after the first month of treatment. BG-12 discontinuation rate was relatively low, suggesting that AEs were effectively managed in a clinical trial setting.

Objectives: To further understand the management of the most common flushing and GI events associated with BG-12 seen in Phase 3 clinical trials and identify potential mitigation strategies for clinical practice.

Methods: The Delphi technique is a widely accepted method of data collection that utilizes iterative rounds of data-gathering and hypothesis-testing questionnaires to build expert consensus on an issue. An initial questionnaire was developed for a sample of investigators involved in the BG-12 Phase 3 clinical trials designed to identify effective approaches for managing patients experiencing flushing or GI events. A second-round questionnaire will be developed to test hypotheses based on data gathered in the first round.

Results: To be eligible for the Delphi panel study, investigators had at least 10 total patients enrolled in DEFINE or CONFIRM. Of the 84 eligible investigators, 50 from a total of 19 countries agreed to participate in the Delphi study panel. Mean number (standard deviation) of patients enrolled at these sites across both DEFINE and CONFIRM for BG-12 twice daily (BID) and BG-12 three times daily (TID) was 5.3 (3.3) and 5.2 (3.2), respectively. Median time on BG-12 was 671 and 672 days for BG-12 BID and BG-12 TID, respectively. The percentage of patients reporting flushing and GI events over 2 years for both BG-12 groups (BID and TID) was 31.4% and 37.9%, respectively. Over 2 years, 1.3% and 19.0% of patients utilized symptomatic therapy for flushing and GI events, respectively, and 1.5% and 4.4% of patients discontinued BG-12 for flushing and GI events, respectively. Results from both questionnaires will be reported.

Conclusions: Data presented here are representative of the total patient population in DEFINE and CONFIRM and reflect a pool of investigators with broad experience managing these events. Results from the BG-12 Delphi panel aim to provide guidance for future management of flushing and GI AEs associated with BG-12 in real-world practice.