The Effectiveness of Plecanatide for Treating Constipation and Bloating in Patients Aged 18 to 40 Years With Irritable Bowel Syndrome: Utilization of a New Composite Trisymptom Endpoint

Background and Aim Irritable bowel syndrome with constipation (IBS‐C) is characterized by multiple sensory symptoms, including abdominal pain, bloating, and bowel habit alterations. Therapeutic response should address all components. This study assesses a new exploratory trisymptom composite efficacy endpoint in an IBS‐C population of young adults with bloating treated with plecanatide. Methods Pooled data were analyzed from two phase 3, randomized, double‐blind trials. Patients (18–40 years) with IBS‐C and baseline bloating (score ≥ 1) received plecanatide 3 mg or placebo for 12 weeks. The composite response definition was simultaneous improvement from baseline in three symptoms (abdominal pain, bloating, and complete spontaneous bowel movements [CSBMs]/week) for ≥ 6 of 12 weeks using several thresholds (≥ 2‐point or ≥ 30% or ≥ 40% improvement in abdominal pain and bloating plus an increase of ≥ 1 or ≥ 2 CSBMs in the same week). Results Six hundred and five adults were included (plecanatide [ n = 313]; placebo [ n = 292]). Plecanatide/placebo baseline mean symptom scores were 6.2/6.4 for abdominal pain and 6.4/6.6 for bloating; both had a mean of 0.2 CSBMs/week. Significantly more patients in plecanatide versus placebo groups ( p ≤ 0.01 for all comparisons) were trisymptom composite responders by several stringent thresholds, including ≥ 30% improvement in pain and bloating plus ≥ 1 CSBM/week increase (23.3% vs. 13.4%; p = 0.002) and ≥ 30% improvement in pain and bloating plus ≥ 2 CSBMs/week increase (19.5% vs. 8.9%; p < 0.001). Plecanatide was well tolerated. Conclusion Plecanatide simultaneously and significantly improved combined symptoms of abdominal pain, bloating, and CSBM frequency at varying thresholds. Plecanatide is effective in improving global IBS‐C symptoms in individuals with bloating. Trial Registration: ClinicalTrials.gov identifiers—NCT02387359 and NCT02493452.