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

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), I-2=60.3% for CD, and (1.52, 95% CI, 0.87-2.63), I-2=56.1% for UC. The corresponding values for acetaminophen use were (1.40, 95% CI, 0.96-2.04), I-2=45.6% for UC, and (1.56, 95% CI, 1.22-1.99), I-2=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.