Role of Nonsteroidal Anti-Inflammatory Drugs in Exacerbations of Inflammatory Bowel Disease

Abstract

GOALS To determine the role of NSAIDs in activation of IBD. BACKGROUND Non-steroidal anti-inflammatory drugs (NSAIDs) may activate inflammatory pathways in inflammatory bowel disease (IBD). STUDY Crohn’s and Colitis Foundation of American (CCFA) Partners is an ongoing cohort study of patients living with IBD. All data are self-reported via the internet. We identified a sub-cohort of participants whose disease activity, based on short Crohn’s Disease Activity Index (sCDAI) and simple clinical colitis activity index (SCCAI), indicated remission. Pattern of use of NSAIDs was measured at baseline, and disease activity assessment was performed 6 months later. We used multivariate binomial regression to determine effects of NSAIDs on disease activity. RESULTS A total of 791 individuals in remission had baseline and follow data available for analysis. Of these, 247 Crohn’s disease (CD) patients (43.2%) and 89 ulcerative colitis (UC) patients (40.6%) reported NSAID use. CD patients with NSAID use ≥ 5 times/monthly had greater risk of active disease at follow-up (23% v. 15%, p=0.04); (adjusted risk ratio (RR) 1.65; 95% confidence interval (CI) 1.12–2.44). No effect was observed in patients with UC (22% vs 21%, p=0.98; adjusted RR 1.25; 95% CI, 0.81–1.92). Acetaminophen use was associated with active disease at follow-up in CD (adjusted RR 1.72, 95% CI 1.11–2.68). CONCLUSIONS Regular (≥ 5 times/monthly) NSAID and acetaminophen use were associated with active CD, but not UC. Less frequent NSAID use was not associated with active CD or UC. These findings indicate that regular NSAID use may increase CD activity, or that NSAID use may be a marker of a less robust remission; thus reflecting subclinical disease activity.

Bradykinin stimulates protein kinase D–mediated colonic myofibroblast migration via cyclooxygenase-2 and heat shock protein 27

“…A growing body of evidence supports the idea that Hsp27 regulates migration of many cell types, possibly through reorganization and polymerization of the actin cytoskeleton [35–37]. COX-2 has been strongly implicated in wound healing, and these findings may partially explain how non-steroidal anti-inflammatory drugs (NSAIDs) may exacerbate IBD [38, 39] or lead to mucosal ulceration [40, 41]. The findings suggest that combination therapies directed at multiple targets may be therapeutically beneficial.…”

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

“…Due to the inherent qualitative differences among studies, we conducted quality assessment using Newcastle‐Ottawa scale (Tables S1 and S2). Studies with a score ≥7 were considered to have low risk of bias, consistent with prior definitions …”

“…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 . 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.…”

Modifiable Environmental Factors in Inflammatory Bowel Disease

“…141 CD patients who reported regular NSAID use ≥5 times/month were at higher risk of active disease at 6 months. 142 A randomized controlled trial of NSAIDs in quiescent IBD demonstrated that one-third of patients relapsed within 7–10 days of initiating therapy 143 while selective COX-2 inhibitors like celecoxib did not have a similar deleterious effect. 144 …”