Abstract
Rectal indomethacin and diclofenac are promising drugs for prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). However, their prophylactic effect on PEP in average-risk patients remains controversial. We performed a systematic review and meta-analysis to assess the efficacy and safety of rectal indomethacin and diclofenac in average-risk patients, and to indirectly compare the prophylactic effect of the two drugs. A comprehensive search of the PubMed, EMBASE, and Cochrane Library databases was performed to identify randomized controlled trials (RCTs) on rectal indomethacin or diclofenac for prophylaxis against PEP. Fixed- and random-effects models weighted by the Mantel-Haenszel method were used for direct comparisons. The adjusted indirect treatment comparison method was used to indirectly compare the efficacy of indomethacin and diclofenac. A total of 10 RCTs, including 2928 patients, met our inclusion criteria. No significant publication bias was identified. Pooled estimates showed that rectal indomethacin and diclofenac were associated with a significant reduction in the overall risk of PEP compared with control intervention [relative risk (RR) = 0.62; 95% confidence interval (CI): 0.46-0.83] in average-risk patients. Subgroup analyses showed that both rectal indomethacin (RR = 0.67; 95% CI: 0.49-0.94) and diclofenac (RR = 0.42; 95% CI: 0.23-0.75) were effective in the prevention of PEP. Indirect comparison showed no significant difference between the effectiveness of the two drugs in the prevention of PEP (RR = 1.607; 95% CI: 0.824-3.136). The updated meta-analysis suggests that both drugs provide equivalent protection against PEP in average-risk patients.