P2363 - Plecanatide Is Efficacious in Patients With Irritable Bowel Syndrome With Constipation (IBS-C) and Bloating: Evaluation Using Trisymptom Composite Endpoints

Darren M.. Brenner, MD¹, Andrea S.. Shin, MD², Adam P.. Laitman, MD³, David C.. Kunkel, MD^4
1Northwestern University, Chicago, IL; ²University of California Los Angeles, Los Angeles, CA; ³Salix Pharmaceuticals, Bridgewater, NJ; ⁴University of California San Diego, La Jolla, CA

Introduction: Patients with IBS have sensory-related symptoms (eg, abdominal pain, bloating). Bloating is one of the most common symptoms identified in patients with IBS-C, with most reporting moderate/severe bloating. The primary aim of this study was to evaluate the efficacy of plecanatide in an IBS-C population with bloating utilizing a novel trisymptom composite endpoint of cardinal symptoms (ie, pain, bloating, and complete spontaneous bowel movements [CSBMs]) at various thresholds of response.

Methods: Data were pooled and analyzed post hoc from 2 identically designed phase 3 trials. Males/females aged 18-40 y with IBS-C and baseline bloating (score ≥ 1) were treated with plecanatide 3 mg or placebo once daily for 12 wk. CSBM frequency and abdominal pain and bloating intensity (scale range, 0-10 for each) were recorded in a daily diary. Response was defined as simultaneous improvement from baseline in all 3 symptoms (abdominal pain, bloating, and CSBMs/wk) for ≥ 6 of 12 wk of treatment using several composite criteria (ie, ≥ 2-point or ≥ 30% or ≥ 40% improvement in abdominal pain and bloating plus an increase of ≥ 1 or ≥ 2 CSBMs in the same wk for ≥ 6 of 12 wk). Patients were also stratified by baseline bloating intensity (mild [score, 1-5]; moderate/severe [score, 6-10]).

Results: 605 adults with IBS-C and bloating (71.6% female; median age, 31.0 y) were included in the analysis (plecanatide [n = 313]; placebo [n = 292]). Plecanatide and placebo baseline mean symptom scores were 6.2 and 6.4 for abdominal pain and 6.4 and 6.6 for bloating, respectively, and both groups had a mean of 0.2 CSBMs/wk. The majority (71.7%) of patients had moderate/severe bloating. Overall, a significantly greater percentage of patients treated with plecanatide vs placebo were trisymptom composite responders, defined using several stringent thresholds (Figure). When stratified by baseline bloating intensity (mild; moderate/severe), significant improvements favoring plecanatide vs placebo were noted for most of the trisymptom composite endpoints (Table).

Discussion: Plecanatide simultaneously and significantly improved abdominal pain, bloating, and CSBM frequency, using varying thresholds to define trisymptom composite responses. These responses were maintained regardless of baseline bloating intensity. Plecanatide appears effective for treating global and individual sensatory and bowel symptoms characteristic of IBS in patients with IBS-C who reported any bloating at the start of therapy.



Disclosures:


Darren M.. Brenner, MD¹, Andrea S.. Shin, MD², Adam P.. Laitman, MD³, David C.. Kunkel, MD⁴. P2363 - Plecanatide Is Efficacious in Patients With Irritable Bowel Syndrome With Constipation (IBS-C) and Bloating: Evaluation Using Trisymptom Composite Endpoints, ACG 2024 Annual Scientific Meeting Abstracts. Philadelphia, PA: American College of Gastroenterology.