Published: Nov 1, 2011
By Joyce Frieden , News Editor, MedPage Today

Action Points

• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• Explain that women who use nonsteroidal anti-inflammatory drugs for 15 or more days per month have a slightly higher risk of developing Crohn’s disease and ulcerative colitis.
• Point out that the absolute risk for developing Crohn’s disease or ulcerative colitis among women who use NSAIDs 15 or more days per month was small (15 per 100,000 for Crohn’s disease compared with nine per 100,00 among nonusers).

WASHINGTON — Women who use nonsteroidal anti-inflammatory drugs — but not aspirin or acetaminophen — have a slightly higher risk of developing Crohn’s disease and ulcerative colitis, a researcher said here.

Compared with nonusers, women who used nonsteroidal anti-inflammatory drugs (NSAIDs) for 15 or more days per month had a relative risk of 1.59 for developing Crohn’s disease (95% CI 0.99 to 2.56), as well as a relative risk of 1.87 for developing ulcerative colitis (95% CI 1.16 to 2.99), Ashwin Ananthakrishnan, MD, of Massachusetts General Hospital in Boston, reported at the American College of Gastroenterology annual meeting.

“Greater frequency, higher dose, and long duration of NSAID use appears to be associated with a twofold increase in risk for Crohn’s disease and ulcerative colitis, but aspirin use is not associated with modification of incidence,” Ananthakrishnan said during his presentation. “Pathways impacted uniquely by NSAIDs and not aspirin may be involved in inflammatory bowel disease pathogenesis.”

Both NSAIDS and aspirin have been associated with gastrointestinal mucosal injury, but they also are thought to lower the risk of colorectal cancer because of their anti-inflammatory properties, Ananthakrishnan and colleagues noted in the background to their study.

However, earlier studies that looked at the association between use of aspirin and NSAIDs and inflammatory bowel disease (IBD) have reported varying results; the effect of aspirin and acetaminophen use on the risk of Crohn’s disease and ulcerative colitis is unknown.

To help shed light on the issue, the investigators conducted a prospective cohort study of 76,814 women enrolled in the Nurses’ Health Study (NHS). Since 1990, study participants have provided data on their use of aspirin and NSAIDs every two years.

The mean age of the cohort in 1990 was 57 years; at baseline, 44% of women reported regular use of aspirin while 37% said they regularly used NSAIDs.

A subgroup of women filled out a supplemental questionnaire in 1990, and most of the pain-reliever users in that group said they used aspirin and NSAIDs analgesically for backache and headache. In 2000, however, among women filling out a similar questionnaire, aspirin was used primarily for cardiovascular disease prevention.

Although there was no clear pattern, current smoking was a little more common among nonusers of NSAIDs compared with those who used them more than 15 days per month, Ananthakrishnan noted.

During 18 years and 1.3 million person-years of follow-up, the researchers found 123 incident cases of Crohn’s disease and 117 cases of ulcerative colitis. Diagnoses of Crohn’s disease and ulcerative colitis were subsequently confirmed by medical record review by two gastroenterologists.

In addition to the increased risk for women who used NSAIDs more than 15 days per month, women who used more than five NSAID tablets per week also had an elevated risk of Crohn’s disease (RR 1.71, 95% CI 1.05 to 2.77) and ulcerative colitis (RR 1.78, 95% CI 1.10 to 2.89), as did women with more than six years of NSAID use (Crohn’s disease: RR 2.83, 95% CI 1.65 to 4.85; ulcerative colitis: RR 2.00, 95% CI 1.15 to 3.49).

On the other hand, dose, duration, or frequency of aspirin or acetaminophen use were not associated with increased risk of either condition.

But frequent NSAID users are not likely to change their habits despite their increased risk because the absolute risk of developing either Crohn’s disease or ulcerative colitis — albeit a statistically significant one — is still quite small, according to Ananthakrishnan.

Among those using NSAIDs 15 or more days per month, the risk of developing Crohn’s disease was 15 per 100,000 compared with nine per 100,00 among nonusers. With ulcerative colitis, the risk rose from nine days per 100,000 in non-NSAID users to 16 days per 100,000 in those that used them more than 15 days per month.

“The incidence of both Crohn’s disease and ulcerative colitis is so low that I don’t think these findings will deter people from taking [NSAIDs],” said Ananthakrishnan. “These are still relatively rare outcomes.”

He said he is uncertain why the risk was elevated with NSAIDs but not with aspirin. “It could be a relative difference in their effects on Cox 1 and Cox 2, [with] selective suppression of one by aspirin and both by nonsteroidals, but I think we need a lot more work on what biologically this result means,” he said.

Limitations of the study included a cohort consisting of mostly white women who were older at diagnosis (average age 61 years), “which we know is higher than the mean age that we traditionally expect from population-based Crohn’s disease and ulcerative colitis studies,” Ananthakrishnan noted. “There also were a small number of cases in each stratum, so that we really did not have the power to look at subgroups that may be at higher risk.”