Lucinda A. Harris, MD1, Jennifer Winters, CRNP1, Andrew Herman, MD2, Sarah Lorenzen, PhD3, Brooks D. Cash, MD, FACG2 1Mayo Clinic, Scottsdale, AZ; 2University of Texas Health Science Center at Houston, Houston, TX; 3Salix Pharmaceuticals, Bridgewater Township, NJ
Introduction: Chronic idiopathic constipation (CIC) is a bothersome functional gastrointestinal disorder associated with varying degrees of abdominal symptoms. Plecanatide, an analogue of human uroguanylin, is approved for the treatment of CIC. This post hoc analysis evaluated the impact of plecanatide on the stool consistency of patients stratified by their Bristol Stool Form Scale (BSFS) score at baseline.
Methods: Patients who met Rome III criteria for CIC were randomized to receive plecanatide 3 mg (PLE) or placebo (PBO) for 12 weeks. Electronic diaries recorded daily straining symptoms using a 5-point Likert scale (0=none; 4=very severe) and daily bowel movements. This analysis evaluated the impact of PLE on changes in stool consistency, straining, frequency of complete spontaneous bowel movements (CSBMs), and durable overall CSBM response rates across 12 weeks. BSFS was recorded at baseline; patients were stratified into 4 subgroups (≤1: n=208, >1‒2: n=611, >2‒3: n=455, and >3: n=412) based on their baseline score. A separate BSFS analysis was conducted in patients indicating “hard stools” as their most bothersome symptom on the Patient Constipation Experience questionnaire.
Results: Overall, significantly more plecanatide-treated patients reported improvements in all endpoints, regardless of their baseline BSFS score. The average change from baseline in stool consistency was the greatest in patients with BSFS scores ≤1 (least-squares mean change: PLE 2.0, PBO 1.4 [P< 0.01]) and >1‒2 (PLE 1.9, PBO 1.2 [P< 0.001]) (Figure 1A). Improvement in straining was consistent with stool consistency across all subgroups, with the greatest improvement in patients with lowest baseline BSFS scores (≤1: PLE ‒1.1, PBO ‒0.7 [P< 0.01]; and >1‒2: PLE ‒1.0, PBO ‒0.7 [P< 0.001]). Plecanatide-treated patients also had significant improvement in average CSBMs/week compared to PBO in all groups (range: PLE 1.6‒2.8, PBO 1.0‒1.5), with 16.7‒30.2% of patients being durable overall CSBM responders compared with PBO (7.5‒16.5%) across 12 weeks. Patients that reported “hard stools” as their most bothersome symptom experienced significant improvement in stool consistency across 12 weeks of treatment (PLE 1.48, PBO 0.89 [P< 0.001]) (Figure 1B).
Discussion: In patients with CIC, response to plecanatide was significantly greater than placebo, regardless of baseline BSFS scores. Plecanatide is an efficacious treatment option for the management of stool consistency and other symptoms of CIC.
Figure: Figure 1. Average Change From Baseline in Stool Consistency (BSFS Score) in (A) CIC Total Population and (B) CIC Patients Reporting “Hard Stools” as Their Most Bothersome Symptom Over 12 Weeks
Lucinda A. Harris, MD1, Jennifer Winters, CRNP1, Andrew Herman, MD2, Sarah Lorenzen, PhD3, Brooks D. Cash, MD, FACG2. P1444 - Plecanatide Improved Stool Consistency in Patients With Chronic Idiopathic Constipation Regardless of Baseline BSFS: A Post-Hoc Analysis, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.