Plecanatide Improves Symptoms of Irritable Bowel Syndrome with Constipation: Results of an Integrated Efficacy and Safety Analysis of Two Phase 3 Trials

• Published in: International journal of general medicine 2023-09, Vol.16, p.3769-3777
• Main Authors: Brenner, Darren M, Dorn, Spencer D, Fogel, Ronald P, Christie, Jennifer, Laitman, Adam P, Rosenberg, Jonathan
• Format: Article
• Language: English
• Subjects: abdominal pain; Analysis; bloating; Constipation; Diarrhea; functional gi disorders; guanylate cyclase-c agonist; Irritable bowel syndrome; Linaclotide; Medical colleges; Original Research
• ISSN: 1178-7074; 1178-7074
• DOI: 10.2147/IJGM.S400431

Purpose: Patients with irritable bowel syndrome with constipation (IBS-C) experience abdominal pain with altered bowel movements. Plecanatide is indicated as IBS-C treatment in adults. This integrated analysis further characterizes plecanatide efficacy and safety in IBS-C. Patients and Methods: Data pooled from 2 identically designed phase 3 trials included adults with IBS-C randomized to plecanatide 3 mg or 6 mg, or placebo once daily for 12 weeks. A daily diary recorded stool frequency/symptoms, with abdominal pain, bloating, cramping, discomfort, fullness, and straining intensity individually rated. Overall response (primary endpoint) was defined as [greater than or equal to]30% improvement from baseline in average worst abdominal pain severity and increase of [greater than or equal to]1 complete spontaneous bowel movement, during same week (composite), for [greater than or equal to]6 of 12 weeks. Secondary endpoints included sustained response (overall response, plus meeting weekly composite criteria during [greater than or equal to]2 of last 4 treatment weeks) and changes from baseline in individual symptoms. Safety assessments included adverse event monitoring. Results: Overall, 2176 patients (74.0% female; mean [SD] age, 43.5 [14.1] years) were included in efficacy analyses (plecanatide 3 mg [n = 724], 6 mg [n = 723], placebo [n = 729]). A significantly greater percentage of patients achieved overall response with plecanatide 3 mg (25.6%) and 6 mg (26.7%) versus placebo (16.0%; both P < 0.001 vs placebo). A significantly greater percentage of patients were sustained responders with plecanatide 3 mg (24.3%) and 6 mg (25.6%) versus placebo (15.6%; both P < 0.001 vs placebo). Significant improvements from baseline in abdominal discomfort, abdominal fullness, abdominal pain, bloating, and cramping occurred as early as Week 1 (Week 2 for abdominal pain) with plecanatide and were maintained through Week 12 versus placebo. Diarrhea, the most common adverse event, occurred in 4.3% (3 mg), 4.0% (6 mg) and 1.0% (placebo) of patients, leading to study discontinuation in 1.2%, 1.4%, and 0 patients, respectively. Conclusion: Plecanatide is safe and effective for treating global and individual IBS-C symptoms. Keywords: abdominal pain, bloating, functional GI disorders, guanylate cyclase-C agonist, irritable bowel syndrome