Bile Acid Sequestrants Demonstrate Significant Benefit As Adjunctive Therapy in Refractory GERD

Bile Acid Sequestrants Demonstrate Significant Benefit As Adjunctive Therapy in Refractory GERD

Prateek Sharma, MD, FASGE, reviewing Vaezi MF, et al. Gastroenterology 2020 Feb 21.

Proton pump inhibitor- (PPI) refractory GERD, accounting for about one-third of all patients with GERD, is a clinically challenging entity. Exposure of the esophagus has been implicated as one of the possible etiologies. This multicenter (n=52), randomized, double-blind placebo-controlled phase 3 study aimed to evaluate the role of IW-3718 (an extended-release formulation of the bile acid sequestrant colesevelam) as an adjuvant to PPI therapy in patients with refractory GERD. 

A total of 280 patients with PPI-refractory GERD (defined as reflux symptoms ≥4 times per week AND receiving ONCE-daily PPI therapy for 8 weeks) were randomized into 4 groups (placebo; or 500 mg, 1000 mg, or 1500 mg of IW-3718) to receive placebo or twice-daily IW-3718, in addition to standard-dose PPI therapy, and were evaluated for improvement in heartburn and regurgitation. There was a significant dose-dependent improvement in heartburn (-46% for placebo; -49%, -55%, and -58% for the 3 doses of IW-3718, respectively; P=.02). Reductions in regurgitation symptoms were also noted (-38% for placebo; -43%, -48%, and -55.4% for the 3 doses of IW-3718, respectively) at 8 weeks compared to baseline. The maximum benefit was noted in the 1500-mg group for heartburn by 5 weeks and regurgitation by 2 weeks and was maintained for the rest of the study period. Adverse events primarily included constipation, nausea, and flatulence; no drug-related serious adverse events were reported.

COMMENT

There is an unmet need to expand the armamentarium for PPI-refractory GERD. Targeting the bile salts and acids in the stomach to counter bile reflux is novel and appears beneficial in patients with refractory GERD. Larger trials are needed to validate the utility of this agent.

Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.

Prateek Sharma, MD, FASGE

CITATION(S)

Vaezi MF, Fass R, Vakil N, et al. IW-3718 reduces heartburn severity in patients with refractory gastroesophageal reflux disease in a randomized trial. Gastroenterology 2020 Feb 21. (Epub ahead of print) (https://doi.org/10.1053/j.gastro.2020.02.031)

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