Rectal Diclofenac Versus Indomethacin in Preventing Post-ERCP Pancreatitis: A Systematic Review and Meta-Analysis

Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) affects up to 9% of average-risk and 40% of high-risk patients. Rectal NSAIDs are guideline-recommended for PEP prophylaxis, yet direct evidence comparing different NSAIDs remains scarce. This study systematically evaluates head-to-head evidence to compare the efficacy of rectal diclofenac versus indomethacin in the prevention of PEP.

This systematic review and meta-analysis adhered to the PRISMA guidelines and was prospectively registered in PROSPERO (CRD420251107055). Eligible studies directly compared rectal diclofenac versus indomethacin for PEP prevention in adults undergoing ERCP. A comprehensive search of five databases was performed through July 2025. Pooled risk ratios with 95% CIs were calculated using fixed- or random-effects models based on heterogeneity, and certainty of evidence was assessed using the GRADE approach.

Four studies (three RCTs, one observational; n = 2,917) compared rectal diclofenac (n = 1,275) and indomethacin (n = 1,642) for PEP prevention. Baseline characteristics were comparable, except for less frequent balloon dilatation with diclofenac (RR 0.78, 95% CI 0.68-0.89; p < 0.001). No significant differences were found for overall PEP (RR 1.17, 95% CI 0.92-1.49; I² = 0%), mild PEP (RR 1.24, 95% CI 0.94-1.63; I² = 0%), moderate PEP (RR 0.60, 95% CI 0.21-1.73; I² = 0%), severe PEP (RR 1.09, 95% CI 0.32-3.77; I² = 1%), or moderate-to-severe PEP (RR 0.97, 95% CI 0.46-2.05; I² = 0%). Secondary outcomes, including mortality and complications, were also similar, with low heterogeneity, indicating equivalent efficacy and safety.

Diclofenac and indomethacin demonstrate equivalent efficacy and safety, allowing cost and availability to inform the choice of PEP prophylaxis.