S534 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

Abstract

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%). Conclusion: Plecanatide 3 mg is an effective and well-tolerated treatment for patients with CIC or IBS-C across various age groups.Figure 1.: Durable Overall CSBM Responder Rate* in Population With CIC, Subgrouped by Age Table 1. - Overall Response Rate* in Population With IBS-C, Subgrouped by Age Age Group Patients, n/n (%) Difference, % P Value Plecanatide 3 mg Placebo < 40 y 72/299 (24.1) 43/283 (15.2) 8.9 0.007 40-59 y 86/317 (27.1) 59/342 (17.3) 9.9 0.002 ≥ 60 y 27/108 (25.0) 15/104 (14.4) 10.6 0.05 *≥ 30% reduction from baseline in worst abdominal pain and increase from baseline of ≥ 1 CSBM/week in the same week for ≥ 6 weeks. CSBM = complete spontaneous bowel movement; IBS-C = irritable bowel syndrome with constipation.