S1148 Efficacy and Safety of Tenapanor in Irritable Bowel Syndrome With Constipation (IBS-C): A Systematic Review and Meta-Analysis

Introduction: Irritable bowel syndrome with constipation (IBS-C) is a common disorder of gut-brain interaction (DGBI) that significantly impacts quality of life. Among the emerging treatments, tenapanor, a sodium/hydrogen exchange inhibitor, shows promise in managing IBS-C. This systematic review and meta-analysis aims to evaluate the efficacy and safety of tenapanor 50 mg compared to placebo. Methods: This systematic review and meta-analysis followed PRISMA guidelines. A literature search was conducted on October 7, 2024, across PubMed, Cochrane, Embase, Scopus, and Web of Science databases. We included randomized controlled trials (RCTs) focusing on adult patients with IBS-C aged 18-75. Quality assessment was performed using the RoB 2 tool. Primary outcomes included responder rates for abdominal symptoms (pain, discomfort, bloating, cramping, fullness) and complete spontaneous bowel movements (CSBM). Secondary outcomes comprised treatment-related adverse events (AEs) and those leading to treatment discontinuation. Data analysis was conducted using R software. Results: Three RCTs were included in the analysis. Tenapanor significantly improved several symptoms in patients with IBS-C compared to placebo. It demonstrated higher response rates for abdominal bloating (RR = 1.32, 95% CI: [1.15, 1.51], P < 0.01), cramping (RR = 1.27, 95% CI: [1.13, 1.44], P < 0.01), discomfort (RR = 1.37, 95% CI: [1.21, 1.56], P < 0.01), fullness (RR = 1.37, 95% CI: [1.20, 1.58], P < 0.01), pain (RR = 1.37, 95% CI: [1.17, 1.49], P < 0.01), and complete spontaneous bowel movements (CSBM) (RR = 1.54, 95% CI: [1.24, 1.91], P < 0.01). However, in terms of safety, tenapanor was associated with a significantly higher incidence of treatment-related adverse events (RR = 2.3, 95% CI: [1.72, 3.06], P < 0.01) and adverse events leading to treatment discontinuation (RR = 9.08, 95% CI: [3.63, 22.71], P < 0.01) when compared to placebo. Diarrhea was a prominent adverse event, occurring significantly more often with tenapanor than placebo (RR = 5.75, 95% CI: [3.44, 9.6], P < 0.01). Conclusion: Tenapanor shows promise as a potential treatment for IBS-C, demonstrating superior efficacy in alleviating symptoms such as abdominal pain, bloating, and discomfort compared to placebo. However, it is associated with a higher incidence of treatment-related adverse events, including those leading to treatment discontinuation. Further prospective, randomized controlled trials are needed to address these safety concerns with diverse patient populations.