NSAIDs & IBD relapse

NSAIDs & IBD relapse

January 10, 2023

Issue 01

Clinical Question

Does NSAID use increase the risk of IBD relapse?

Editor’s Bottom Line

The observed association between NSAID use and IBD exacerbation may not be causative. This should reassure IBD patients who can benefit from NSAID therapy.


Cohen-Mekelburg S, Van T, Wallace B, et al. The Association Between Nonsteroidal Anti-Inflammatory Drug Use and Inflammatory Bowel Disease Exacerbations: A True Association or Residual Bias? Am J Gastroenterol. 2022;117(11):1851–57; https://journals.lww.com/ajg/Abstract/2022.aspx


Aiming to shed light on the purported link between non-steroidal anti-inflammatory drug (NSAID) use and IBD exacerbations, researchers analyzed data from a cohort of 35,031 patients with IBD treated in the Veterans Affairs health system in the United States between 2004 and 2015. IBD exacerbations were defined as any outpatient IBD-related health care encounter resulting in at least one week of corticosteroid use. Patients administered NSAIDs were propensity-matched to patients not exposed to NSAIDs.

The mean follow-up was 5.9 years and patients were a mean 60 years of age at the index date. The most prescribed NSAIDs were ibuprofen, naproxen and etodolac. 

Results of a multivariate analysis adjusting for a range of possible confounding variables found a 24% increased risk of IBD exacerbation among those who received NSAIDs (Hazard Ratio [HR]: 1.24; 95% Confidence Interval [CI], 1.16–1.33). However, the investigators also found that, the likelihood of an IBD exacerbation was already greater among those exposed to NSAIDs (HR: 1.30; 95% CI, 1.21–1.39) during the year prior to NSAID exposure.

Moreover, a sub analysis of 3,968 patients in the cohort, who were exposed to NSAIDs and subsequently experienced an IBD exacerbation, revealed similar rates of IBD exacerbation in the year preceding exposure and in the 2 weeks to 6 months after NSAID use. There was a higher incidence of IBD exacerbation up to two weeks after NSAID exposure, suggesting the possibility that NSAIDs may have been initiated in response to increasing IBD-related symptoms.


Study Design: Retrospective cohort analysis

Funding: The National lnstitutes of Health, Glaxo-Wellcome Institute for Digestive Health, VA Health Services

Allocation: Not applicable

Setting: Multicenter

Level of Evidence: 2b