S532 Plecanatide Improves Severe Abdominal Pain and Severe Bloating in Individuals With Irritable Bowel Syndrome With Constipation (IBS-C): A Pooled Analysis of Two Phase 3 Trials

Abstract

Introduction: IBS-C is a disorder of gut-brain interaction characterized by abdominal pain related to defecation and hard stool consistency. Bloating is also amongst the most common symptoms. Plecanatide is indicated in the United States for the treatment of IBS-C in adults. The aim of this study was to evaluate the efficacy of plecanatide for severe abdominal pain and/or severe bloating in patients with IBS-C. Methods: Data were pooled and analyzed post hoc from two phase 3, randomized trials of adults with IBS-C treated with plecanatide 3 mg (FDA-approved dose) or placebo once daily for 12 weeks (NCT02387359; NCT02493452). Patients rated abdominal pain and bloating severity separately using an 11-point scale (0 [none] to 10 [worst possible]). A subgroup analysis was conducted in patients with severe pain, severe bloating, or both at baseline. Symptom scores ≥ 8 were defined as severe. Response was defined as a ≥ 30% improvement from baseline in symptom score(s) at Week 12. A correlation analysis measured the strength of associations between abdominal pain and bloating. A coefficient (r) value of > 0.90-1.00 was considered very strong positive correlation; > 0.70-0.90, strong positive correlation. Results: At baseline, 285 (19.6%) of 1453 patients reported severe abdominal pain, 311 (21.4%) reported severe bloating, and 233 (16.0%) reported both symptoms as severe. A significantly greater percentage of plecanatide-treated patients with severe baseline abdominal pain were responders vs placebo at Week 12 (Δ=14.6%, P=0.01 [Figure]). In addition, a significantly greater percentage of plecanatide-treated patients with severe baseline bloating treated were responders vs placebo at Week 12 (Δ=14.9%; P=0.005 [Figure]). In patients with both symptoms rated severe at baseline, a numeric difference favored plecanatide vs placebo (Δ=12.9%; P=0.05 [Figure]). In the overall and severe pain/bloating patient subgroups, changes from baseline to Week 12 in abdominal pain and bloating were strongly correlated to each other (overall population: r=0.85-0.88; both severe subgroup, r=0.92-0.95; Table). Conclusion: In patients with IBS-C and severe abdominal pain and/or severe bloating, plecanatide treatment reduced symptom severity vs placebo, with strong correlations in symptom responses. This suggests a parallel pathogenesis and associated generalized improvement in the visceral hypersensitivity underlying these symptomsFigure 1.: Percentage of Patients With ≥ 30% Improvement From Baseline in Severe Abdominal Pain, Bloating, or Both at Week 12, by Subgroup Table 1. - Correlation of Change From Baseline at Week 12 in Abdominal Pain and Bloating Symptoms in Overall Population and Those With Severe Baseline Abdominal Pain and Bloating Population Abdominal pain and bloating Spearman correlation coefficient, r Pearson correlation coefficient, r Overall population 0.85* 0.88* Severe abdominal pain and bloating population 0.92* 0.95* *P < 0.001 .