Comparison of the Efficacy and Safety of Different Doses of Linaclotide for Patients with Chronic Constipation: A Meta-Analysis and Bayesian Analysis

BACKGROUND: It is ambiguous whether a higher dose of linaclotide provides higher efficacy for chronic constipation (CC) patients. The meta-analysis aimed to assess the efficacy and safety of linaclotide doses ranging from 62.5 μg to 600 μg for CC patients. METHODS: A comprehensive search was conducted, and STATA16 software was used for data analysis. RESULTS: Seven studies with 4,107 patients were eligible. A significantly enhanced number of completely spontaneous bowel movement (CSBM) responders were found in the extremely low-dose group (OR: 2.94; 95% CI: 1.98–4.34; p < 0.001), the low-dose group (OR: 3.24; 95% CI: 2.44–4.31; p < 0.001), the medium-dose group (OR: 3.08; 95% CI: 1.46–6.50; p=0.003), and high-dose group (OR: 4.79; 95% CI: 3.04–7.54; p < 0.001). Bayesian analysis showed the high-dose group obtained the maximum CSBM responder rate (OR: 4.94; 95% credible interval (CrI): 3.22–7.79; probability rank = 0.87) indirectly compared with extremely low-dose, low-dose, and medium-dose groups. However, no significant difference presented in the CSBM responder rate by pairwise comparisons of the different dose groups. Additionally, no more any adverse events occurred in the higher linaclotide dose group (RR: 0.91; 95% CrI: 0.60–1.38) indirectly compared with other dose groups. CONCLUSIONS: High dose of linaclotide could be more effective and safer for CC patients, which need more trials to confirm in the future.