Different doses of prucalopride in treating chronic idiopathic constipation: a meta-analysis and Bayesian analysis

OBJECTIVE: This study aims to explore the incremental benefit of different doses of prucalopride in treating chronic idiopathic constipation (CIC). METHODS: PubMed, EMBASE, MEDLINE, Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, VIP medicine information and Wanfang databases were comprehensively searched up to March 2020. Prospective trials with different doses of prucalopride versus placebo were selected. The frequency of spontaneous bowel movements (SBMs) per week and the treatment-emergent adverse events (TEAEs), such as headache, arrhythmia, diarrhoea, dizziness, nausea and vomiting, were first synthesised in a meta-analysis. The probability of optimal dose of prucalopride was then ranked by random-effects within Bayesian analysis. RESULTS: 14 high-quality randomised controlled trials with 4328 patients were ultimately included. SBMs per week increased significantly after using 1 mg (OR: 2.40, 95% CI 1.32 to 4.37), 2 mg (OR: 2.55, 95% CI 1.93 to 3.36) and 4 mg (OR: 2.51, 95% CI 1.92 to 3.28) prucalopride. Bayesian analysis demonstrated 1 mg dose obtained the maximum SBMs per week (OR: 3.31, 95% credible interval 1.72 to 6.16, probability rank=0.70) indirectly compared with 2 mg and 4 mg doses. TEAEs were higher significantly in 2 mg (risk ratio (RR): 1.20, 95% CI 1.09 to 1.33) and 4 mg (RR: 1.14, 95% CI 1.07 to 1.22) prucalopride. The 1 mg dose did not reach statistical significance (RR: 1.17, 95% CI 0.94 to 1.44). CONCLUSIONS: The study concludes that 1 mg dose at commencement could be safer in treating CIC and that 2 mg prucalopride could be more efficacious in terms of SBMs per week outcome receiving. PROSPERO REGISTRATION NUMBER: CRD42019136679.