November 2, 2011 (National Harbor, Maryland/Washington, DC) — High doses of nonsteroidal anti-inflammatory drugs (NSAIDs), longer duration of use, or greater frequency of use are all associated with an increased risk for Crohn's disease and ulcerative colitis, according to findings of a study presented here at the American College of Gastroenterology (ACG) 2011 Annual Scientific Meeting.

In contrast, although both aspirin and NSAIDs are associated with ulcerations in the gastrointestinal tract, dose, duration, and frequency of aspirin use were not associated with risk for Crohn's disease or ulcerative colitis. The authors distinguished between aspirin and other NSAIDs in their study.

"So this suggests that there may be pathways uniquely affected by NSAIDs and not by aspirin," Ashwin Ananthakrishnan, MD, MPH, a gastroenterologist on staff at Massachusetts General Hospital, Boston, and an instructor at Harvard Medical School, told Medscape Medical News. "Such pathways could potentially be important in explaining why some people get Crohn's and ulcerative colitis."

Compared with nonusers, women who used NSAIDs for more than 15 days a month faced a greater risk for Crohn's disease and ulcerative colitis. Women who used more than 5 tablets of NSAIDs per week also saw an elevated risk for Crohn's disease compared with women with more than 6 years of NSAID use.

Although significant advances have been made in understanding the genetics of Crohn's disease and ulcerative colitis, with up to 99 genetic variations associated with the 2 conditions, genetic changes explain only about one third of the risk for the diseases, suggesting that environment has a big influence on why someone gets either Crohn's disease or ulcerative colitis, said Dr. Ananthakrishnan, who was lead author on the study.

The researchers conducted a prospective cohort study of 76,814 women enrolled in the Nurses' Health Study (NHS). Since 1990, the NHS has captured data on aspirin and NSAID use. Gastroenterologists subsequently confirmed diagnoses of Crohn's disease or ulcerative colitis.

The data drew upon more than 18 years of data, including 123 confirmed incident cases of Crohn's disease and 117 cases of ulcerative colitis. The mean age of the cohort in 1990 was 57 years. The researchers used Cox proportional hazards models to examine the relative risks for Crohn's disease and ulcerative colitis after adjusting for possible confounders, including smoking, menopausal status, and hormone use. In all, 44% of women reported regular use of aspirin and 37% said they regularly used NSAIDs at baseline.

Dr. Ananthakrishnan cautioned against overinterpreting the results of the study. "It's very important to recognize you have to weigh the risks and benefits," he said. For someone who doesn't have Crohn's or ulcerative colitis, the absolute risk is fairly small. Perhaps 15 in 100,000 people risk getting the conditions.

More studies are needed to compare the safety of these agents, he said, noting that people are more likely to take high-dose NSAIDs and take NSAIDs more frequently for pain relief. Those who take aspirin for cardiac protection tend to take low doses. "We don't know if you take the same dose of NSAIDs or aspirin, if they are equally safe or equally dangerous," he said.

Bruce Sands, MD, MS, chief of the Division of Gastroenterology and Burrill B. Crohn professor of medicine at Mount Sinai Hospital in New York, New York, said he found the study "a very provocative, interesting, and well-done work."

"The risk of NSAIDS for IBD [inflammatory bowel disease] has long been speculated due to their effects in decreasing barrier function of the gut epithelium. This is the first study to prospectively assess that risk in advance of onset of disease to my knowledge," he told Medscape Medical News.

Dr. Ananthakrishnan has disclosed no relevant financial relationships. Dr. Sands has financial relationships with Abbott Immunology, Avaxia Biologics, Bristol-Myers Squibb, Elan Pharmaceuticals, Emmi Solutions, GlaxoSmithKline, Novartis Pharmaceuticals, Pfizer, and Prometheus Laboratories.

American College of Gastroenterology (ACG) 2011 Annual Scientific Meeting and Postgraduate Course. Abstract #6. Presented October 31, 2011.

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