SAN DIEGO – Commonly used pain medications increase the risk of exacerbations of Crohn’s disease, judging from the findings of a prospective cohort study of nearly 800 patients with inflammatory bowel disease initially in remission.

Patients with Crohn’s disease who used nonsteroidal anti-inflammatory drugs (NSAIDs) at least five times monthly were 65% more likely to have active disease 6 months later, investigators reported at the annual meeting of the American College of Gastroenterology. Unexpectedly, any use of acetaminophen was also an independent risk factor in this group.

"A lot of our patients in remission are taking these medications. We need to ask detailed histories about this," she added. It is noteworthy that no such effect was seen in ulcerative colitis patients. "There might be a dose/response issue here. We have a lot of young women obviously with inflammatory bowel disease who take ibuprofen for menstrual cramping." When taken fewer than five times monthly, these drugs do not seem to have an effect, she noted.

"Implications may be that the requirement for any pain medication while in remission may actually be a marker of occult ongoing disease. Occult disease itself may be the risk factor for disease activity," commented lead investigator Dr. Millie Long, an assistant professor at the University of North Carolina, Chapel Hill.

"It’s also theoretically possible that a mechanism common to both drugs may be associated with increased disease activity," she added. For example, both NSAIDs and acetaminophen inhibit cyclooxygenase-3.

"Further prospective studies are needed with objective inflammatory outcomes to better assess the risks of these pain medications and better counsel patients," Dr. Long maintained.

One audience member noted that the study could not tease apart whether analgesic use was the cause or the result of an exacerbation.

"I would argue that we specifically limited this to a population of patients in remission by validated disease activity indices at baseline. ... We also had data on the quality of life of these individuals, the Shortened Inflammatory Bowel Disease questionnaire. These were individuals who felt well," Dr. Long replied. "That said, they could have been taking their pain medication for gut pain, I agree. They could have been taking it for arthritis, they could have been taking it for a headache."

Session comoderator Dr. Miguel D. Regueiro, a gastroenterologist at the University of Pittsburgh, asked, "In your practice, will you allow Crohn’s patients to take an NSAID three or four times a month?"

"I do, particularly for my young women who really need it for menstrual cramping. I don’t think that one time a week – and obviously these data support that – is going to cause a problem," Dr. Long replied. "I do feel these data as well as the Bonner prospective cohort data [Inflamm. Bowel Dis. 2004;10:751-57] show that high-dose NSAIDs may be bad news in patients with Crohn’s disease."

The investigators conducted the study among Crohn’s and Colitis Foundation of America (CCFA) Partners, an Internet-based cohort of patients with inflammatory bowel disease. The patients completed online surveys at baseline and 6 months, answering questions about disease activity and average number of times per month they used various pain medications.

Analyses were based on 791 patients who were in remission at baseline. About 75% had Crohn’s disease, reported Dr. Long. The mean duration of inflammatory bowel disease was approximately 14 years.

Overall, 43% of patients reported using any NSAIDs, and 19% reported using them at least five times monthly. Additionally, 65% reported any use of acetaminophen.

At follow-up, about a fifth of patients overall had experienced an exacerbation and now had active disease, defined as a simplified Crohn’s Disease Activity Index (sCDAI) score of at least 150 or a Simple Clinical Colitis Activity Index (SCCAI) score of greater than 2.

In the cohort as a whole, the proportion of patients with an exacerbation did not vary significantly according NSAID use, but it was higher among acetaminophen users versus nonusers (20% vs. 14%; P = .03).

Analyses stratified by type of disease showed that patients with Crohn’s disease were more likely to have an exacerbation if they used NSAIDs at least five times monthly versus less often, and if they used acetaminophen at all. In contrast, patients with ulcerative colitis were not affected.

In multivariate analyses that controlled for potential confounders, including use of other medications, NSAID use five or more times monthly was an independent risk factor for exacerbation in the entire cohort (relative risk, 1.46) and in the subset with Crohn’s disease (RR, 1.65).

Any use of acetaminophen was also an independent risk factor, both in the entire cohort (RR, 1.41) and in the subset with Crohn’s disease (RR, 1.72).

Dr. Long disclosed no relevant conflicts of interest.

Common analgesics linked to flares of Crohn’s disease