CHICAGO – Rectal indomethacin reduced by 90% the risk of post-procedural pancreatitis in patients with primary sclerosing cholangitis.

The anti-inflammatory has already been shown to reduce the risk of acute pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in a general population, Nikhil Thiruvengadam, MD, said at the annual Digestive Disease Week^®. Now, his retrospective study of almost 5,000 patients has shown the drug’s benefit in patients with primary sclerosing cholangitis (PSC), who are at particularly high risk of pancreatitis after the procedure.

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The study also identified some patient characteristics that further increase the risk for post-ERCP pancreatitis (PEP), Dr. Thiruvengadam of the University of Pennsylvania, Philadelphia, said in a video interview.

“A prior history of PEP and a difficult initial cannulation were significant risk factors for developing PEP,” he said. “Indomethacin significantly reduced this risk, and our findings suggest that future prospective trials studying pharmacological prophylaxis of PEP – including rectal indomethacin – should be powered to be able detect a difference in PSC patients, and they should be included in such studies.”

In 2016 Dr. Thiruvengadam and his colleagues showed that rectal indomethacin significantly reduced the risk of PEP by about 65% in a diverse group of patients, including those with malignant biliary obstruction (Gastroenterology. 2016;151:288–97). The new study used an expanded patient-cohort but focused on patients with PSC, as they require multiple ERCPs for diagnosis and stenting of strictures and cholangiocarcinoma screening and thus may be more affected by post-procedural pancreatitis.

The study comprised 4,764 patients who underwent ERCP at the University of Pennsylvania from 2007-2015; of these, 200 had PSC. Rectal indomethacin was routinely administered to patients beginning in June 2012. The primary outcome of the study was post-ERCP pancreatitis. The secondary outcome was the severity of post-ERCP pancreatitis.

PEP was about twice as common in the PSC group as in the overall cohort (6.5% vs. 3.8%). Moderate-severe PEP also was twice as common (4% vs. 2%).

Dr. Thiruvengadam broke down the cohort by indication for ERCP. These included PSC as well as liver transplant, choledocholithiasis, benign pancreatic disease, bile leaks, and ampullary adenoma. PSC patients had the highest risk of developing PEP – almost 3 times more than those without the disorder (OR 2.7).

Among PSC patients, age, gender, and total bilirubin were not associated with increased risk. A history of prior PEP increased the risk by 17 times, and a difficult initial cannulation that required a pre-cut sphincterotomy increased it by 15 times.

“Interestingly, dilation of a common bile duct stricture reduced the odds of developing PEP by 81%,” Dr. Thiruvengadam said.

He then examined the impact of rectal indomethacin on the study subjects. Overall, PEP developed in 5% of those who didn’t receive indomethacin and 2% of those who did. In the PSC group, PEP developed in 11% of those who didn’t get indomethacin and less than 1% of those who did.

Indomethacin was particularly effective at preventing moderate-severe PEP, Dr. Thiruvengadam noted. In the overall cohort, moderate-severe PEP developed in 3% of unexposed patients compared to 0.6% of those who received the drug. The difference was more profound in the PSC group: None of those treated with indomethacin developed moderate-severe PEP, which occurred in 9.3% of the unexposed group.

Generally, patients who have previously undergone a sphincterotomy are at lower risk for PEP, Dr. Thiruvengadam said, and this was reflected in the findings for the overall group: PEP developed in 3% of the untreated patients and 0.5% of the treated patients. Post-sphincterotomy patients with PSC, however, were still at an increased risk of PEP. Indomethacin significantly mitigated this – no patient who got the drug developed PEP, compared with 10.5% of those who didn’t get it.

A series of regression analyses confirmed the consistency of these findings. In an unadjusted model, rectal indomethacin reduced the risk of post-ERCP PEP by 91% in patients with PSC. A model that adjusted for common bile duct brushing, type of sedation, and common bile duct dilation found a 90% risk reduction. Another model that controlled for classic risk factors for PEP (age, gender, total bilirubin, history of PEP, pancreatic duct injection and cannulation, and pre-cut sphincterotomy) found a 94% risk reduction.

“We additionally performed a propensity score matched analysis to account for potential unmeasured differences between the two cohorts, and it also confirmed the results found and demonstrated that indomethacin significantly reduced the odds of developing PEP by 89%,” Dr. Thiruvengadam said.

He had no financial conflicts of interest to disclosures.

Digestive Disease Week^® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).

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VIDEO: Indomethacin slashes post-ERCP pancreatitis risk in primary sclerosing cholangitis