Kyle Staller, MD, MPH1, Jimmy Hinson, PharmD2, René Kerstens, MSc3, William Spalding, MS2, Anthony J. Lembo, MD, FACG4; 1Massachusetts General Hospital, Boston, MA; 2Shire, a Takeda company, Lexington, MA; 3Orion Statistical Consulting BV, Hilvarenbeek, Noord-Brabant, Netherlands; 4Beth Israel Deaconess Medical Center, Boston, MA
Introduction: Prucalopride is a selective serotonin type 4 (5-HT4) agonist indicated for the treatment of chronic idiopathic constipation (CIC) in adults. Patients with CIC frequently experience abdominal bloating. To further assess the effect of prucalopride on abdominal bloating, a post hoc analysis of data from six clinical trials was performed in a subset of patients with CIC who had moderate to very severe bloating at baseline. Methods: Data from the 12-week time point of five phase 3, and one phase 4, randomized, double-blind, placebo-controlled trials of prucalopride (2 mg once daily for 12 or 24 weeks) were pooled. Abdominal bloating is one of 12 items assessed by the Patient Assessment of Constipation Symptoms questionnaire, which uses a 5-point scale (0–4). Patients included in this analysis had a baseline abdominal bloating score of moderate (2), severe (3) or very severe (4). Bloating responders were defined as patients with an improvement of ≥ 1 point in abdominal bloating score from baseline to week 12 (those without a week 12 score were considered non-responders). Analyses were also performed in patients grouped by main complaint at baseline. In addition, the percentage change in abdominal bloating score over time and the proportion of patients with a bloating score of 0–1 (minimal bloating) at week 12, were assessed. Results: Overall, 1931/2484 patients (77.7%; prucalopride, n = 957; placebo, n = 974) had moderate to very severe bloating at baseline (mean age, 46.7 years; 79.0% women; mean baseline bloating score, 2.8). At week 12, a greater proportion of prucalopride-treated patients were bloating responders compared with those who received placebo (62.1% vs 49.6%). Bloating responder rates were higher in the prucalopride group (57.9–69.3%) than in the placebo group (41.4–53.3%), irrespective of main complaint at baseline (Fig. 1). From week 2 onwards, the percentage improvement in abdominal bloating score was greater in the prucalopride group than in the placebo group (Fig. 2). At week 12, 43.7% of patients who received prucalopride had minimal bloating compared with 30.1% of those who received placebo (Fig. 3). Discussion: Over 75% of patients with CIC who participated in phase 3 or 4 clinical trials of prucalopride had moderate to very severe abdominal bloating at baseline. Prucalopride improved symptoms of abdominal bloating to a greater extent than placebo in this patient population throughout the treatment period, irrespective of main complaint at baseline.
Figure 1. Proportion of patients with CIC and moderate to very severe abdominal bloating at baseline who had an improvement of ≥ 1 point in abdominal bloating score* according to main complaint at baseline
Figure 2. Percentage change in abdominal bloating score* over time in patients with CIC who had moderate to very severe abdominal bloating at baseline
Figure 3. Proportion of patients with CIC and moderate to very severe abdominal bloating at baseline who had minimal abdominal bloating* at week 12
Disclosures: Kyle Staller: Shire, a Takeda company – Consultant, Speaker's Bureau. Takeda – Grant/Research Support. Jimmy Hinson: Shire, a Takeda company – Employee. Takeda – Stockholder/Ownership Interest (excluding diversified mutual funds). René Kerstens: Orion Statistical Consulting BV – Employee. Shire Human Genetic Therapies, Inc., a Takeda company – Grant/Research Support. William Spalding: Shire, a Takeda company – Employee. Takeda – Stockholder/Ownership Interest (excluding diversified mutual funds). Anthony Lembo: Shire, a Takeda company – Consultant, Grant/Research Support.