Association between health-related quality of life and symptoms in patients with chronic constipation: An integrated analysis of three phase 3 trials of prucalopride

Abstract

Background: Prucalopride is a high-affinity 5-HT4 receptor agonist for the treatment of chronic constipation. The aims of this study were to investigate the relationship between health-related quality of life (HRQoL) and symptoms of constipation, and to assess the response of HRQoL to treatment using integrated data from three phase III trials of prucalopride. Methods: This was an integrated analysis of data from three pivotal multicenter, double-blind, randomized, placebo-controlled, parallel-group trials (ClinicalTrials.gov Identifiers: NCT00488137, NCT00483886 and NCT00485940). Relationships were investigated between Patient Assessment of Constipation Quality of Life (PAC-QOL) scores, Patient Assessment of Constipation Symptoms (PAC-SYM) scores, bowel movement frequency (assessed using daily diaries), and treatment. Key Results: Patients treated with prucalopride 2 mg (n = 659) and placebo (n = 661) were included in the analysis. An improvement in PAC-SYM scores correlated well with an improvement in PAC-QOL overall score (r = 0.711) and satisfaction subscale score (r = 0.589). After 12 weeks, PAC-QOL overall score and satisfaction subscale score significantly (p < 0.001) improved by ≥1 point (clinically relevant) in 36.5% and 44.1% of patients treated with prucalopride, compared with 18.5% and 22.4% with placebo respectively. Moreover, 39.0% of patients with an improvement in satisfaction of ≥1 point achieved ≥3 spontaneous complete bowel movements/week, compared with 7.4% of those with no improvement in satisfaction (<1 point). Conclusions & Inferences: Improvements in PAC-QOL overall score and satisfaction score were associated with improvements in symptoms of chronic constipation. Compared with placebo, treatment with prucalopride significantly improved HRQoL. This was an integrated analysis of data from three pivotal multicenter, double-blind, randomized, placebo-controlled, parallel-group trials or prucalopride in patients with chronic constipation. The data from the three trials were pooled, and correlations were assessed for the change from baseline in PAC-QOL overall and satisfaction subscale scores compared with PAC-SYM scores. There was a strong correlation (r = 0.710) between improvement in PAC-SYM and improvement in PAC-QOL scores. PAC-SYM scores also correlated well with the PAC-QOL satisfaction subscale (r = 0.589).