NSAIDs may be tolerable for IBD patients with significant musculoskeletal symptoms, particularly those with ulcerative colitis, according to a US study challenging longstanding safety concerns.

The analysis of nearly 350,000 patients found NSAID use was not associated with a meaningful increase in IBD-related hospitalisation in ulcerative colitis patients compared with unexposed patients. A definitive conclusion could not be reached for Crohn’s disease.

Researchers matched 80,710 NSAID-exposed patients (23% of the cohort) to two or three unexposed patients each, using inverse probability of treatment weighting to adjust for confounders.

Using a prespecified non-inferiority margin of HR 1.2, the results were:

NSAID exposure significantly increased risk of all-cause hospitalisation, likely reflecting known associations with acute kidney injury and adverse cardiac events, the researchers said. A definitive determination for gastrointestinal surgery could not be made due to wide confidence intervals around this rarer outcome.

The researchers noted that over half of NSAID-exposed patients had at least one recent code for joint or chronic musculoskeletal pain, consistent with prior data suggesting inflammatory arthritis or enthesitis affects up to half of IBD patients.

Writing in Arthritis Care & Research [link here], the researchers argued the 2018/2019 American College of Gastroenterology (ACG) guidelines’ blanket recommendation against NSAID use, irrespective of IBD subtype or NSAID formulation, was too broad, leaving clinicians and patients “with imperfect alternatives for analgesia, such as opioids or increased immunosuppression.”

They said their findings were more consistent with the 2024 European Crohn’s and Colitis Organisation (ECCO) guidelines, which recommend case-by-case risk/benefit assessment of NSAIDs in IBD patients with arthropathy, noting that risk may be lower in ulcerative colitis and with short-term COX-2 selective inhibitor use.

Why Crohn’s disease patients appeared more vulnerable was unclear, but the researchers suggested the broader anatomic involvement of Crohn’s disease, including the upper gastrointestinal tract where NSAID toxicity is most common, was a possible explanation.

Professor Jane Andrews

Gastroenterologist Professor Jane Andrews, board chair and medical director of Crohn’s Colitis Cure, welcomed the findings.

“This is a huge dataset and they have really not found any signal,” she said. “Where they have found a small signal, you wonder, were those people taking nonsteroidals for abdominal pain or for joints that were flaring because their IBD was active?”

Professor Andrews said the findings reflected a shift already underway in clinical practice. Thirty years ago, fewer patients achieved endoscopic remission, and apparent NSAID-related flares may have represented unmasked, under-treated IBD rather than true drug toxicity, she said.

“My experience is that using nonsteroidals in people with IBD seems to be a bit of a non-issue, particularly if their IBD is well-controlled,” she said, adding that clinician concern about NSAIDs had waned as the drugs became widely available over the counter without an apparent increase in IBD complications.

The researchers called for prospective studies to provide further clarity.