The Association Between Nonsteroidal Anti-Inflammatory Drug Use and Inflammatory Bowel Disease Exacerbations: A True Association or Residual Bias?

Abstract

INTRODUCTION:Studies suggest that nonsteroidal anti-inflammatory drugs (NSAID) may contribute to inflammatory bowel disease (IBD) exacerbations. We examined whether variation in the likelihood of IBD exacerbations is attributable to NSAID.METHODS:In a cohort of patients with IBD (2004–2015), we used 3 analytic methods to examine the likelihood of an exacerbation after an NSAID exposure. First, we matched patients by propensity for NSAID use and examined the association between NSAID exposure and IBD exacerbation using an adjusted Cox proportional hazards model. To assess for residual confounding, we estimated a previous event rate ratio and used a self-controlled case series analysis to further explore the relationship between NSAID and IBD exacerbations.RESULTS:We identified 15,705 (44.8%) and 19,326 (55.2%) IBD patients with and without an NSAID exposure, respectively. Findings from the Cox proportional hazards model suggested an association between NSAID and IBD exacerbation (hazard ratio 1.24; 95% confidence interval 1.16–1.33). However, the likelihood of an IBD exacerbation in the NSAID-exposed arm preceding NSAID exposure was similar (hazard ratio 1.30; 95% confidence interval 1.21–1.39). A self-controlled case series analysis of 3,968 patients who had both an NSAID exposure and IBD exacerbation demonstrated similar exacerbation rates in the 1 year preceding exposure, 2–6 weeks postexposure, and 6 weeks to 6 months postexposure, but a higher incidence in 0–2 weeks postexposure, suggesting potential confounding by reverse causality.DISCUSSION:While we see an association between NSAID and IBD exacerbations using traditional methods, further analysis suggests this may be secondary to residual bias. These findings may reassure patients and clinicians considering NSAID as a nonopioid pain management option.

Causes, Diagnostic Testing, and Treatment of Residual Symptoms in Patients With IBD With Quiescent Disease

“…Although abdominal pain may mirror previous flares, similar principles should be observed including avoidance of opioid medications. A recent study makes the case for limited use of nonsteroidal anti-inflammatory drugs in outpatients with documented quiescent disease (14). Alternatively, COX-2 inhibitors can be used.…”

Older Adult-Onset of Inflammatory Bowel Diseases Is Associated With Higher Utilization of Analgesics: A Nationwide Cohort Study

“…Pain may be related to bowel inflammation, extraintestinal manifestations, or gastrointestinal surgery, among other etiologies. Various classes of analgesics are used, including strong opioids (e.g., morphine, oxycodone, hydromorphone), weak or synthetic opioids (e.g., tramadol, codeine), nonsteroidal antiinflammatory drugs (NSAID), and paracetamol (i.e., acetaminophen) (4,5). The clinical management of pain with analgesics requires careful consideration because of adverse effects such as addiction, gastrointestinal toxicities, severe infection, and mortality (4).…”

A True Residual Bias: Did the Exacerbation Truly Precede NSAID Exposure?

“…Elizabeth Squirell, MD, MS 1 and Brian Bressler, MD, MS 1 Am J Gastroenterol 2023;118:1462. https://doi.org/ 10.14309/ajg.0000000000002262…”

“…Cohen-Mekelburg et al (1) have done exemplary work in studying the risks associated with nonsteroidal inflammatory drugs (NSAIDs) in those with inflammatory bowel disease (IBD). The correlation between NSAID use and IBD exacerbations is one that, anecdotally, limits our ability to comfortably manage multifactorial pain in those with inflammatory bowel disease.…”