Rectal Diclofenac Likely Comparable to Rectal Indomethacin for Post-ERCP Pancreatitis

NEW YORK (Reuters Health) – An exploratory network analysis of post-retrograde cholangiopancreatography (ERCP) prophylaxis suggests that rectal diclofenac can be used interchangeably with rectal indomethacin to reduce costs, researchers say.

“At least 50 different prophylactic agents were investigated for the prevention of post-ERCP pancreatitis (PEP), and based on the current evidence, a few categories of prophylactic agents appear to be most promising,” Dr. Venkata Akshintala of Johns Hopkins Medical Institutions in Baltimore told Reuters health by email. “These include non-steroidal anti-inflammatory drugs (NSAIDs), intravenous fluid administration and pancreatic duct stent placement.”

“However,” he noted, “there have been many variations in dose, route of delivery, and subtypes of drugs or stents, making it challenging for practitioners to select the best prophylaxis for their patients.” Thus, the current study compares the various agents and combinations.

“Rectal indomethacin was the most commonly studied and frequently recommended NSAID for PEP prophylaxis, but we were pleasantly surprised that rectal diclofenac is at least equivalent or potentially superior to (it),” he said. “This has huge cost implications in the U.S., due to the steep increase in the cost of rectal indomethacin – from $2 for 100 mg in 2005 to $340 in 2019.”

“We also identified that supplementing rectal NSAIDs with intravenous fluid may provide an additive prophylactic advantage against PEP,” he said.

As reported in The Lancet Gastroenterology and Hepatology, 55 randomized controlled trials evaluating 20 interventions in more than 17,000 patients were included in the network meta-analysis.

The mean incidence of post-ERCP pancreatitis in the placebo or active control groups was 12.2%. In pairwise comparisons, normal saline plus rectal indomethacin (OR 0.02), intramuscular diclofenac 75 mg (0.24), intravenous high-volume Ringer’s lactate plus rectal diclofenac 100 mg (0.30), intravenous high-volume Ringer’s lactate (0.31), 5-7-Fr pancreatic stents (0.35), rectal diclofenac 100 mg (0.36), 3-Fr pancreatic stents (0.47), and rectal indomethacin 100 mg (0.60, 0.50-0.73) were all more efficacious than placebo for preventing PEP.

Compared to rectal indomethacin 100 mg, the 5-7 Fr pancreatic stents (0.59), intravenous high-volume Ringer’s lactate plus rectal diclofenac 100 mg (0.49), intravenous standard-volume normal saline plus rectal indomethacin 100 mg (0.04), and rectal diclofenac 100 mg (0.59) were more efficacious.

The GRADE confidence rating was low-to-moderate for 98.3% of the pairwise comparisons.

The authors conclude, “Rectal diclofenac 100 mg is the best performing rectal NSAID in this network meta-analysis. Combinations of prophylaxis might be more effective, but there is little evidence. These findings help to establish prophylaxis of post-ERCP pancreatitis for future research and practice, and could reduce costs and increase adoption of prophylaxis.”

Dr. Akshintala said, “We were also able to obtain individual patient-level data, which we are utilizing to conduct a patient-level meta-analysis and apply machine-learning methods that we are hoping will provide a more personalized PEP prophylaxis for each patient.”

Dr. Venkataraman Muthusamy, director of endoscopy at UCLA Heath, commented by phone to Reuters Health, “The study confirms what many of us have suspected – that a combination of therapies appears to be better than each alone.”

“While prospective affirmative studies are needed,” he said, “the researchers took great pains to adjust for variables and have provided reliable ‘sneak peak’ evidence that would have otherwise taken years if not decades to amass.”

“In the U.S., rectal indomethacin has gotten more expensive,” he noted, “so the study’s finding that a rectal diclofenac dose of 100 mg may be as good, if not better, is valuable information for clinicians.”

“Further study will be needed to determine the optimal combination of treatment modalities.

SOURCE: The Lancet Gastroenterology and Hepatology, online June 29, 2021.

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