Should IBD patients avoid prescription NSAIDs?

Despite the reported adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in individuals with inflammatory bowel disease (IBD), a study presented at Crohn’s and Colitis Congress 2026 appears to show otherwise.

“The concern that NSAIDs may precipitate flares of IBD has limited their use in managing musculoskeletal symptoms in this population, but safety data are mixed,” the investigators said.

“[In our study,] prescription NSAID exposure was associated with a numerically small risk of IBD-related hospitalization below the prespecified noninferiority threshold. The risk was not observed in patients with ulcerative colitis, while small-magnitude risks were present among individuals with Crohn’s disease,” they added.

In the IPTW* Cox model, NSAID exposure was associated with a small increase in IBD-related hospitalization in the overall IBD cohort (hazard ratio [HR], 1.08, 95 percent confidence interval [CI], 1.05–1.11). However, it failed to cross the prespecified noninferiority margin of 1.2 based on a clinically acceptable risk defined by IBD content experts, the researchers explained.

When stratifying by IBD subtypes, the increase in IBD-related hospitalization was evident among patients with Crohn’s disease (HR, 1.16, 95 percent CI, 1.11–1.21), but not among those with ulcerative colitis (HR, 0.96, 95 percent CI, 0.91–1.01). As with the overall cohort, noninferiority was not met. [CCC 2026, abstract izag006.004]

For NSAID-exposed patients, the adjusted IBD-related hospitalizations were 0.06 events/person-year, whereas in the unexposed group, the corresponding rate was 0.05 events/person-year. A comparison between groups yielded an absolute risk difference of 0.007, with a number needed to harm of 137.

There were higher rates of gastrointestinal surgery (overall HR, 1.23, 95 percent CI, 1.19–1.28) and all-cause hospitalization (overall HR, 1.30, 95 percent CI, 1.28–1.32) with prescription NSAID exposure, but neither met the noninferiority criteria.

Multiple contrasting evidence

Several studies have investigated the association between NSAID use and the onset or relapse of IBD; however, most of these show conflicting results. [Pharmaceuticals (Basel) 2010;3:1084-1092]

Some studies show that IBD can cause the reactivation of quiescent disease, induce gastrointestinal complications, exacerbate IBD, or trigger a relapse. [Clin Gastroenterol Hepatol 2006;4:196-202; Am J Gastroenterol 2001;96:1306-1308; Am J Gastroenterol 2009;104:1298-1313; Dig Dis Sci 2006;51:168-172]

Other trials did not show any association between active or quiescent Crohn’s disease or ulcerative colitis and NSAID use. [Am J Gastroenterol 2000;95:1946-1948; Inflamm Bowel Dis 2004;10:751-757]

Acceptable risks

The investigators conducted a retrospective cohort study of patients with IBD from the Optum’s de-identified Clinformatics Data Mart Database (2000–2022). Individuals with a new NSAID prescription fill were matched with individuals without an NSAID fill during the study period by age and calendar year when IBD criteria were met. Participants were censored at the end of continuous enrolment, end of study period, or ≥6 months from the last NSAID fill.

Among 271,236 individuals with IBD, 29.7 percent were NSAID-exposed. All covariates were balanced across groups after IPTW.

“[Taken together,] the results challenge the current paradigm of avoiding NSAIDs in all patients with IBD and suggest that NSAID risks may be acceptable for many patients with significant joint disease,” the researchers concluded.