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Systematic review with meta-analysis: association between acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) and risk of Crohn's disease and ulcerative colitis exacerbation.

ABSTRACT: BACKGROUND:Unlike acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) have generally been thought to be associated with increased risk of IBD exacerbation. AIM:To carry out a systematic review and meta-analysis of previous studies examining the association between acetaminophen and NSAIDs including cyclooxygenase (COX-2) inhibitors use, and risk of Crohn's disease (CD) and ulcerative colitis (UC) exacerbation. METHODS:We identified published manuscripts and abstracts through 1 March 2017 by systematic search of Medline, Embase, Cochrane and other trial registries. Quality assessment was done using Newcastle-Ottawa scale and random-effect meta-analysis using pooled relative risks (RRs) and 95% CIs were calculated. RESULTS:Eighteen publications between years 1983 and 2016 were identified. For the meta-analysis, pooled RRs of disease exacerbation with NSAIDs use were (1.42, 95% CI, 0.65-3.09), I2 = 60.3% for CD, and (1.52, 95% CI, 0.87-2.63), I2 = 56.1% for UC. The corresponding values for acetaminophen use were (1.40, 95% CI, 0.96-2.04), I2 = 45.6% for UC, and (1.56, 95% CI, 1.22-1.99), I2 = 0.0% for IBD. Sensitivity analyses limited to studies with low risk of bias showed a significantly increased risk of CD exacerbation (1.53, 95% CI, 1.08-2.16) but not UC (0.94, 95% CI, 0.36-2.42) with NSAIDs use. CONCLUSIONS:Contrary to generally accepted belief, we did not find a consistent association between NSAIDs use and risk of CD and UC exacerbation. There was also no consistent evidence for association with acetaminophen although further studies are needed.

SUBMITTER: Moninuola OO

PROVIDER: S-EPMC5992031 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Systematic review with meta-analysis: association between acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) and risk of Crohn's disease and ulcerative colitis exacerbation.

Moninuola O O OO Milligan W W Lochhead P P Khalili H H

Alimentary pharmacology & therapeutics 20180405 11

<h4>Background</h4>Unlike acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) have generally been thought to be associated with increased risk of IBD exacerbation.<h4>Aim</h4>To carry out a systematic review and meta-analysis of previous studies examining the association between acetaminophen and NSAIDs including cyclooxygenase (COX-2) inhibitors use, and risk of Crohn's disease (CD) and ulcerative colitis (UC) exacerbation.<h4>Methods</h4>We identified published manuscripts and abstrac ...[more]

PMID: 29620794

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Project description:Clostridium difficile infection (CDI) is a major public health threat worldwide. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with enhanced susceptibility to and severity of CDI; however, the mechanisms driving this phenomenon have not been elucidated. NSAIDs alter prostaglandin (PG) metabolism by inhibiting cyclooxygenase (COX) enzymes. Here, we found that treatment with the NSAID indomethacin prior to infection altered the microbiota and dramatically increased mortality and the intestinal pathology associated with CDI in mice. We demonstrated that in C. difficile-infected animals, indomethacin treatment led to PG deregulation, an altered proinflammatory transcriptional and protein profile, and perturbed epithelial cell junctions. These effects were paralleled by increased recruitment of intestinal neutrophils and CD4+ cells and also by a perturbation of the gut microbiota. Together, these data implicate NSAIDs in the disruption of protective COX-mediated PG production during CDI, resulting in altered epithelial integrity and associated immune responses.IMPORTANCE Clostridium difficile infection (CDI) is a spore-forming anaerobic bacterium and leading cause of antibiotic-associated colitis. Epidemiological data suggest that use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk for CDI in humans, a potentially important observation given the widespread use of NSAIDs. Prior studies in rodent models of CDI found that NSAID exposure following infection increases the severity of CDI, but mechanisms to explain this are lacking. Here we present new data from a mouse model of antibiotic-associated CDI suggesting that brief NSAID exposure prior to CDI increases the severity of the infectious colitis. These data shed new light on potential mechanisms linking NSAID use to worsened CDI, including drug-induced disturbances to the gut microbiome and colonic epithelial integrity. Studies were limited to a single NSAID (indomethacin), so future studies are needed to assess the generalizability of our findings and to establish a direct link to the human condition.

Dataset Information

Systematic review with meta-analysis: association between acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) and risk of Crohn's disease and ulcerative colitis exacerbation.

Publications

Systematic review with meta-analysis: association between acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) and risk of Crohn's disease and ulcerative colitis exacerbation.

Similar Datasets

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