New Agent for Refractory Reflux

In the June issue of Gastroenterology (158: 2015-16), a tribute to George Sachs (1935-2019) recognizes his work in the field of gastroenterology and his development of proton pump inhibitors (PPIs).

Much more work remains as ~30% of patients with gastroesophageal reflux remain symptomatic despite PPI therapy.   In the same issue, IW-3718, a bile acid sequestrant colsevelam with a gastric-retentive formulation was studied in 280 patients (MF Vaez et al. Gastroenterol 2020; 158: 2017-19).

Methods: The authors performed a multicenter, double-blind, placebo-controlled 8-weel treatment trial (2016-17); patients received the study drug (500, 1000, 1500 mg) or placebo twice daily.  The authors enrolled symptomatic patients (≥4 times per week) with erosive esophagitis or pathologic reflux based on Bravo study (pH<4 for ≥4.2% during at least one 24-hour period). They continued PPI therapy which they had been receiving for a minimum of 8 weeks prior to starting study medication.

Key findings:

  • Improvement in heartburn severity scores for placebo, 500, 1000, and 1500 mg groups: 46%, 49%, 55%, and 58%.  The 11.9% difference between 1500 mg group compared to placebo reached statistical significance (P=.04)
  • There was an improvement in weekly regurgitation frequency score as well from baseline to week 8 in 1500 mg group of 17.5% compared to placebo.
  • No serious drug related serious adverse events were identified.  Constipation was noted in 8% of study drug recipients compared 7% for placebo recipients.

Limitations: lack of a centralized review for endoscopy images, high placebo response rate, once daily use of PPI in study, and problems with overlap of functional symptoms

My take: This study shows why a placebo control is needed in reflux studies.  While IW-3718 at higher doses was effective, its response appears much less notable when compared with placebo-recipients.

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