The rectal NSAID indomethacin reduced the rate of pancreatitis in both low- and high-risk patients undergoing endoscopic retrograde cholangiopancreatography, according to the results of a retrospective study published in Gastroenterology.
“This study was undertaken to try to answer some of the unanswered questions surrounding post-ERCP pancreatitis (PEP) risk reduction in real-world practice,” Michael L. Kochman, MD, AGAF, FASGE, Wilmott Family Professor of Medicine, Center for Endoscopic Innovation, Research, and Training in the gastroenterology division at University of Pennsylvania Health System, told Healio Gastroenterology. “We reviewed our clinical experience with the near universal use of rectal indomethacin in patients felt to be at risk for pancreatitis simply by virtue of undergoing ERCP.”
Kochman and colleagues retrospectively evaluated 4,017 patients (823 with malignant biliary obstruction) who underwent ERCP at the Hospital of the University of Pennsylvania between 2009 and 2015. No ERCP patients received indomethacin before routine administration of 100 mg after procedures began in June 2012.
The investigators collected data on demographic and clinical features, procedures and development of PEP, and used multivariable logistic regression to calculate adjusted odds ratios for the associations between indomethacin and PEP.
“In our view most of the findings were not surprising: the clinical impact of PEP reduction holds even for patients felt to be at low-risk for PEP,” Kochman said.
PEP occurred in 1.99% of the 2,007 patients who received indomethacin and in 4.73% of the 2,010 patients who did not.
Rectal indomethacin reduced the risk for developing PEP by 65% (OR = 0.35; 95% CI, 0.24-0.51; P < .001) and reduced the risk for developing moderate-to-severe PEP by 83% (OR = 0.17; 95% CI, 0.09-0.32; P < .001).
Moreover, among patients with malignant biliary obstruction, it reduced the risk for developing PEP by 64% (OR = 0.36; 95% CI, 0.17-0.75; P < .001) and reduced the risk for developing moderate-to-severe PEP by 80% (OR = 0.2; 95% CI, 0.07-0.63; P < .001).
The greatest benefit was seen in high-risk patients with pancreatic adenocarcinoma, with 2.31% of those who received rectal indomethacin developing PEP compared with 7.53% who did not receive indomethacin (P < .001) and 0.59% vs. 4.32% developing moderate-to-severe PEP (P = .001).
Subgroup analyses showed indomethacin also significantly reduced the risk for developing PEP and moderate-to-severe PEP in patients with gallstones, bile leaks and primary sclerosing cholangitis, and showed a trend toward benefit in post-orthotropic liver transplantation patients.
Similar rates of post-procedural GI bleeding occurred between patients who did and did not receive indomethacin (0.65% vs. 0.45%), no differences in perforation rates were observed and no allergic reactions occurred.
“Given the low cost and low risk of the drug we feel that wider use of it should help minimize patients’ risk when ERCP is performed,” Kochman said.
While these findings represent good news for biliary endoscopists and their ERCP patients, they also conflict with prospective data from Levenick and colleagues that found indomethacin did not reduce PEP rates, according to a related editorial by Healio Gastroenterology board member Douglas G. Adler, MD, FACG, AGAF, FASGE, from the division of gastroenterology and hepatology at University of Utah School of Medicine in Salt Lake City.
Douglas G. Adler
“The paper by Thiruvengadam et al strongly endorses the routine use of indomethacin as a means to prevent PEP, whereas Levenick et al sharply disagree with this approach and, I suspect, would discourage routine use of rectal indomethacin for this purpose,” Adler wrote. “Until the issue is settled, I suspect most endoscopists already using these agents routinely in their ERCP practice will continue to do so given their low risk and the potential, if yet fully undefined, benefits they may offer.” – by Adam Leitenberger
The researchers and Adler report no relevant financial disclosures.