Systematic Review With Meta-analysis

Association Between Acetaminophen and Nonsteroidal Anti–inflammatory Drugs (NSAIDs) and Risk of Crohn's Disease and Ulcerative Colitis Exacerbation

O. O. Moninuola; W. Milligan; P. Lochhead; H. Khalili

Disclosures

Aliment Pharmacol Ther. 2018;47(11):1428-1439. 

In This Article

Abstract and Introduction

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), 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.

Introduction

Unlike acetaminophen, nonsteroidal anti–inflammatory drugs (NSAIDs) have generally been thought to be associated with increased risk of IBD exacerbation. Use of NSAIDs is known to be associated with mucosal ulcers in the gastrointestinal tract.[1–3] In addition, chronic use of NSAIDs has previously been linked to development of Crohn's disease (CD) and ulcerative colitis (UC).[4–7] In clinical practice, patients with established IBD are encouraged to avoid the use of NSAIDs because of the concern for their potential adverse effects on disease activity and instead are encouraged to use acetaminophen for management of pain. Although several studies have examined the link between NSAIDs use and IBD exacerbation, the results have been conflicting.[6,8,9] We therefore sought to conduct a systematic review and meta–analysis of prior studies examining the relationship between acetaminophen, NSAIDs and cyclooxygenase (COX–2) inhibitors use, and risk of IBD exacerbation. Such comprehensive examination of prior studies may ultimately help inform clinical recommendations for patients with established IBD.

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