Prevention of post‐endoscopic retrograde cholangiopancreatography pancreatitis with a combination of pharmacological agents based on rectal non‐steroidal anti‐inflammatory drugs: A systematic review and network meta‐analysis

Background and Aims Rectally administered non‐steroidal anti‐inflammatory drugs (NSAIDs) are effective but suboptimal in the prevention of post‐endoscopic retrograde cholangiopancreatography pancreatitis or PEP. New trials with the combination of rectal NSAIDs and other pharmacological agents have been conducted. This network meta‐analysis (NMA) aimed to determine the relative efficacy of combination regimens and identify an optimal regimen for preventing PEP. Methods We performed a systematic and comprehensive search to identify and analyze all the randomized controlled studies published until October 15, 2019, examining rectal NSAIDs and their combination with other pharmacological agents for the prevention of PEP. The primary outcome was the frequency of PEP. We conducted an NMA to combine the direct and indirect comparisons of rectal NSAIDs and their combination with other pharmacological agents. Results The NMA included 24 studies evaluating 14 regimens in 11 321 patients. According to predictive interval plot and surface under the cumulative ranking curve values, indomethacin + lactated Ringer's solution, followed by diclofenac + nitrate and indomethacin + normal saline, is the most efficacious combination of pharmacological agents for the overall prevention of PEP. Rectal indomethacin alone is the most efficacious agent for prevention of moderate to severe PEP, and rectal diclofenac is the most useful agent for prevention of PEP among the high‐risk group. Conclusions Rectal indomethacin with intravenous hydration and rectal diclofenac with sublingual nitrate are the most efficacious combination regimens for the overall prevention of PEP.