Proton pump inhibitors exacerbate NSAID-induced small bowel injury: A prospective, double-blind, randomized trial.
Clin Gastroenterol Hepatol. 2015 Oct 29;
Authors: Washio E, Esaki M, Maehata Y, Miyazaki M, Kobayashi H, Ishikawa H, Kitazono T, Matsumoto T
Abstract
BACKGROUND & AIMS: Some studies have reported a high incidence of small bowel injuries in 60%-80% of subjects who take non-selective non-steroidal anti-inflammatory drugs (NSAIDs) and PPIs simultaneously. We performed a randomized, double-blind, controlled study to determine whether proton pump inhibitors (PPIs) exacerbate NSAID-induced small bowel injury.
METHODS: Fifty-seven healthy subjects were randomly assigned groups given the NSAID celecoxib (200 mg, twice daily) plus placebo for 2 weeks (COX-2 SI group) or celecoxib plus the PPI rabeprazole (20 mg, once daily) for 2 weeks (COX-2 SI+PPI group). The study was performed October 2012 to September 2013 at a tertiary medical center in Japan. All subjects were evaluated by capsule endoscopy at the start of the study and then after 2 weeks administration of the test articles. The incidence rates and the numbers of small bowel injuries (ulcers and erosions) that were observed under capsule endoscopy were compared between groups. The primary endpoint was the incidence of mucosal injuries at the second capsule endoscopy examination.
RESULTS: The overall incidence of small bowel injury was significantly higher in the COX-2 SI+PPI group (12 of 27 subjects, 44.4%) than in the COX-2 SI group (5 of 30 subjects, 16.7%, P= .04). The COX-2 SI+PPI group had a significantly increased risk of small bowel injury in comparison to the COX-2 SI group (relative risk 2.67; 95% confidence interval, 1.08-6.58). The number of erosions in each subject was greater in the COX-2 SI+PPI group than in the COX-2 SI group (P= .02). The number of ulcers didn't differ between the two groups. The incidence of mucosal injury in the jejunum was significantly higher in the COX-2 SI+PPI group than in the COX-2 SI group (26% vs. 0%, P = .003), whereas no such trend found in the ileum.
CONCLUSIONS: In a randomized, controlled trial, we found that PPIs increase the risk of short-term NSAID-induced small bowel injury. UMIN clinical trial registry number: UMIN000008883.
PMID: 26538205 [PubMed - as supplied by publisher]