The effectiveness of indomethacin and pancreatic duct stenting in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis: A systematic review and network meta-analysis.

Abstract

Background and aims: Endoscopic retrograde cholangiopancreatography (ERCP) has significant diagnostic and therapeutic roles in pancreaticobiliary disorders. Post-ERCP pancreatitis (PEP) is the most common adverse event that can be encountered and affects 1% to 9% of the average-risk group and 11% to 40% of the high-risk group. Several methods have been used to prevent PEP, including pancreatic duct (PD) stenting and pharmacological use, including indomethacin.

Methods: We conducted a systematic review of PubMed (MEDLINE), Scopus and Web of Science (WOS) databases until November 1, 2024, using relevant keywords. Only randomized clinical trials (RCTs) were included. The network meta-analysis is reported using odds ratios (ORs) with 95% confidence intervals (CIs) with a significance level < 0.05. Rank probabilities were calculated using p-scores to rank treatments based on their effectiveness. All analyses were performed using R version 4.3.1 (2023-06-16 ucrt) with the netmeta package. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) assessment of the certainty of the evidence was performed.

Results: Of 1828 references, total 31 RCTs with 9050 participants were included in this meta-analysis. Compared to placebo, indomethacin (OR = 0.50, 95% CI = 0.39-0.64, p < 0.001), PD stenting (OR = 0.33, 95% CI = 0.23-0.47, p < 0.001) and indomethacin combined with PD stenting (OR = 0.36, 95% CI = 0.18-0.73, p = 0.005) were effective in reducing PEP. Sub-group analysis of high-risk patients revealed similar results, indomethacin (OR = 0.43, 95% CI = 0.31-0.61, p < 0.001), PD stenting (OR = 0.32, 95% CI = 0.22-0.47, p < 0.001) and indomethacin combined with PD stenting (OR = 0.32, 95% CI = 0.14-0.72, p = 0.006). Notably, indomethacin did not show significant effects in mild, moderate or severe PEP. Notably, indomethacin showed significant benefit in the prevention of moderate-severe PEP only.

Conclusions: The present network meta-analysis indicated that PD stenting seems to be the most effective in reducing PEP incidence among the examined treatments, particularly in high-risk patients, with inconsistent benefits of indomethacin in different PEP severities.