D0269 - Plecanatide Improves Symptoms of Chronic Idiopathic Constipation (CIC) and Irritable Bowel Syndrome With Constipation (IBS-C) Across Age Subgroups: An Analysis of Four Phase 3 Trials

Kyle Staller, MD, MPH¹, Adam Laitman, MD², Christopher Allen, MS², Leila Neshatian, MD, MSc³, William D Chey, MD⁴, Lin Chang, MD^5
1Massachusetts General Hospital, Boston, MA; ²Salix Pharmaceuticals, Bridgewater, NJ; ³Stanford University School of Medicine, Stanford, CA; ⁴University of Michigan, Michigan Medicine, Ann Arbor, MI; ⁵University of California, Los Angeles, Los Angeles, CA

Introduction: CIC and IBS-C are common disorders of gut-brain interaction that may exist on a disease severity continuum. Plecanatide is a guanylate cyclase-C agonist approved in the US for treatment of adults with CIC or IBS-C. The aim of this analysis was to evaluate the potential impact of age on plecanatide efficacy in CIC and IBS-C.

Methods: Data were analyzed post hoc from two CIC (NCT01982240; NCT02122471) and two IBS-C (NCT02387359; NCT02493452) randomized, phase 3 trials of adults treated with plecanatide 3 mg (FDA-approved dose) or placebo once daily for 12 weeks. Data were pooled by indication and subgrouped by age (< 40 y, 40-59 y, and ≥ 60 y). The primary protocol-defined efficacy endpoint for CIC trials was the percentage of durable overall complete spontaneous bowel movement (CSBM) responders (≥ 3 CSBMs/week and increase from baseline of ≥ 1 CSBM for same week for ≥ 9 weeks, including ≥ 3 of last 4 treatment weeks [ie, durable]). For the IBS-C trials, the endpoint was the percentage of overall responders (≥ 30% reduction from baseline in worst abdominal pain and increase from baseline of ≥ 1 CSBM/week in the same week for ≥ 6 weeks). Treatment-emergent adverse events (AEs) also were evaluated by age group.

Results: Of the 1762 patients with CIC, 638 (36.2%) were < 40 y, 783 (44.4%) were 40-59 y, and 341 (19.4%) were ≥ 60 y. Of the 1453 patients with IBS-C, 582 (40.1%) were < 40 y; 659 (45.4%) were 40-59 y, and 212 (14. 6%) were ≥ 60 y. For CIC, significantly more plecanatide-treated patients were durable overall CSBM responders vs placebo in all 3 age subgroups (Figure). For IBS-C, significantly more plecanatide-treated patients were overall responders vs placebo in the < 40 y and 40-59 y subgroups, whereas a numeric difference favoring plecanatide was observed for the ≥ 60 y subgroup (Table). In the plecanatide group, the number of patients with ≥ 1 AE slightly increased with age for CIC (< 40 y, 29.2%; 40-59 y, 31.2%; ≥ 60 y, 35.1%) and IBS-C (< 40 y, 23.4%; 40-59 y, 23.4%; ≥ 60 y, 25.9%). Rates of diarrhea-related discontinuation in plecanatide-treated patients were low overall, occurring most often in the group aged 40-59 y for both CIC (< 40 y, 1.6%; 40-59 y, 2.6%; ≥ 60 y, 2.3%) and IBS-C (< 40 y, 0.3%; 40-59 y, 2.2%; ≥ 60 y, 0.9%).

Discussion: Plecanatide 3 mg is an effective and well-tolerated treatment for patients with CIC or IBS-C across various age groups.




Disclosures:


Kyle Staller, MD, MPH¹, Adam Laitman, MD², Christopher Allen, MS², Leila Neshatian, MD, MSc³, William D Chey, MD⁴, Lin Chang, MD⁵. D0269 - Plecanatide Improves Symptoms of Chronic Idiopathic Constipation (CIC) and Irritable Bowel Syndrome With Constipation (IBS-C) Across Age Subgroups: An Analysis of Four Phase 3 Trials, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.