Role of Non-Steroidal Anti-inflammatory Drugs in Exacerbations of Inflammatory Bowel Disease

Abstract

Purpose: Inflammatory bowel diseases (IBD) are chronic immunologic diseases of the gastrointestinal (GI) tract characterized by periods of exacerbation and remission. Data are limited as to causative factors of exacerbations. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for pain, and have been reported to lead to exacerbations of IBD. We aimed to determine rates of NSAID use in the IBD population, and whether NSAID use increases the risk of exacerbation of IBD. Methods: We identified individuals with Crohn's disease (CD) or ulcerative colitis (UC) in remission at baseline evaluation within Crohn's and Colitis Foundation of America (CCFA) Partners, an online IBD cohort. We determined current patterns NSAID use, and then assessed disease activity 6 months later. NSAID exposure was evaluated in a dichotomous fashion (any/none and ≥5 times /<5 times monthly). We used bivariate statistics and binomial regression models to assess the independent effects of NSAID use on disease exacerbation. Results: A total of 711 individuals with IBD (519 with CD and 192 with UC) in remission, based on short Crohn's disease activity index (sCDAI <150) or simple clinical colitis activity index (SCCAI ≤2) reported NSAID use patterns. Disease activity was assessed 6 months later. A total of 308 (43.3%) reported any NSAID use, 146 (20.5%) reported ≥5 uses/month, and 125 (17.6%) met criteria for a flare at 6-month follow up. Those on any NSAIDs flared at similar rates to those not on any NSAIDS (19.5% vs. 16.1%, p=0.25). Results were similar when stratified by CD or UC. Those with ≥5 uses/month were more likely to flare when compared to those with <5 uses/month (24.0% vs. 15.9%, p=0.02), risk ratio (RR) 1.50 (95% confidence interval [CI] 1.07-2.13) overall IBD, RR 1.22 (95% CI 0.64-2.33) for UC, and RR 1.66 (95% CI 1.10-2.50) for CD. After controlling for smoking, IBD medication use, and acetaminophen use, the results for overall IBD remained similar (adjusted RR 1.46; 95% CI 1.03-2.08). Acetaminophen use was also independently associated with flare of disease (adjusted RR 1.57, 95% CI 1.08-2.27). Conclusion: NSAID use is common amongst individuals with IBD in remission. Those reporting ≥5 uses/month of NSAIDs had a significantly higher risk of flare when compared to those with <5 uses/month. However, those using acetaminophen also had an increased risk of flare, demonstrating that the requirement for any pain medication while in remission may be a marker of occult disease, or that a mechanism common to both drugs (cyclooxygenase-2 or 3 inhibition) may be associated with flare.