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Aspirin, Nonsteroidal Anti-inflammatory Drug Use, and Risk for Crohn Disease and Ulcerative Colitis: A Cohort Study

Ashwin N. Ananthakrishnan, MD, MPH; Leslie M. Higuchi, MD, MPH; Edward S. Huang, MD, MPH; Hamed Khalili, MD; James M. Richter, MD; Charles S. Fuchs, MD, MPH; and Andrew T. Chan, MD, MPH
[+] Article, Author, and Disclosure Information

Acknowledgment: The authors thank Gideon Aweh for his computer programming expertise.

Grant Support: By the American Gastroenterological Association (Dr. Ananthakrishnan), the Broad Medical Research Foundation (Dr. Chan), the IBD Working Group (Dr. Khalili), and the National Institutes of Health (R01 CA137178, P01 CA87969, P30 DK043351, and K08 DK064256).

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-1760.

Reproducible Research Statement:Study protocol and data set: Not available. Statistical code: Available from Dr. Ananthakrishnan (e-mail, mailto:aananthakrishnan@partners.org).

Requests for Single Reprints: Andrew T. Chan, MD, MPH, Gastrointestinal Unit, Massachusetts General Hospital, 55 Fruit Street, GRJ 722, Boston, MA 02114; e-mail, mailto:achan@partners.org.

Current Author Addresses: Dr. Ananthakrishnan: 165 Cambridge Street, 9th Floor, Boston, MA 02114.

Dr. Higuchi: Children's Hospital, GI/Nutrition, Hunnewell Ground, 300 Longwood Avenue, Boston, MA 02115.

Drs. Huang, Khalili, and Chan: Gastrointestinal Unit, Massachusetts General Hospital, 55 Fruit Street, GRJ 722, Boston, MA 02114.

Dr. Richter: Blake Building, 4th Floor, 55 Fruit Street, Boston, MA 02114.

Dr. Fuchs: Dana-Farber Cancer Institute, Department of Medical Oncology, 44 Binney Street, Boston, MA 02115.

Author Contributions: Conception and design: A.N. Ananthakrishnan, J.M. Richter, C.S. Fuchs, A.T. Chan.

Analysis and interpretation of the data: A.N. Ananthakrishnan, E.S. Huang, H. Khalili, J.M. Richter, C.S. Fuchs, A.T. Chan.

Drafting of the article: A.N. Ananthakrishnan, J.M. Richter, C.S. Fuchs, A.T. Chan.

Critical revision of the article for important intellectual content: A.N. Ananthakrishnan, L.M. Higuchi, E.S. Huang, H. Khalili, J.M. Richter, C.S. Fuchs, A.T. Chan.

Final approval of the article: A.N. Ananthakrishnan, E.S. Huang, H. Khalili, J.M. Richter, C.S. Fuchs, A.T. Chan.

Provision of study materials or participants: C.S. Fuchs, A.T. Chan.

Statistical expertise: A.N. Ananthakrishnan, H. Khalili, A.T. Chan.

Obtaining of funding: A.N. Ananthakrishnan, A.T. Chan.

Administrative, technical, or logistic support: C.S. Fuchs, A.T. Chan.

Collection and assembly of data: L.M. Higuchi, H. Khalili, J.M. Richter, C.S. Fuchs, A.T. Chan.

From Harvard Medical School, Massachusetts General Hospital, Children's Hospital Boston, Brigham and Women's Hospital, and the Dana-Farber Cancer Institute, Boston, Massachusetts.

Ann Intern Med. 2012;156(5):350-359. doi:10.7326/0003-4819-156-5-201203060-00007
Text Size: A A A

Background: Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are anti-inflammatory but have been linked in some studies to Crohn disease (CD) and ulcerative colitis (UC).

Objective: To assess the association between aspirin and NSAID use and incident CD and UC.

Design: Prospective cohort study.

Setting: Nurses' Health Study I.

Patients: 76 795 U.S. women who provided biennially updated data about aspirin and NSAID use.

Measurements: Incident CD and UC between 1990 and 2008 (outcome) and NSAID and aspirin use (exposure).

Results: 123 incident cases of CD and 117 cases of UC occurred over 18 years and 1 295 317 person-years of follow-up. Compared with nonusers, women who used NSAIDs at least 15 days per month seemed to have increased risk for both CD (absolute difference in age-adjusted incidence, 6 cases per 100 000 person-years [95% CI, 0 to 13]; multivariate hazard ratio, 1.59 [CI, 0.99 to 2.56]) and UC (absolute difference, 7 cases per 100 000 person-years [CI, 1 to 12]; multivariate hazard ratio, 1.87 [CI, 1.16 to 2.99]). Less frequent NSAID use was not clearly associated with risk for CD or UC, and there was no clear association between aspirin use and disease.

Limitations: Cohort participants were exclusively women, most of whom were white. Aspirin and NSAID use were self-reported.

Conclusion: Frequent use of NSAIDs but not aspirin seemed to be associated with increased absolute incidence of CD and UC. The findings have more mechanistic than clinical implications, because the absolute incidence of CD or UC associated with NSAIDs was low and the increase in risk for CD or UC associated with NSAIDs is unlikely to alter the balance of more common and clinically significant risks and benefits associated with these agents.

Primary Funding Source: American Gastroenterological Association, IBD Working Group, Broad Medical Research Program, and National Institutes of Health.


Grahic Jump Location

Figure 1. Study flow diagram.

CD = Crohn disease; IBD = inflammatory bowel disease; UC = ulcerative colitis.

Grahic Jump Location
Grahic Jump Location

Figure 2. Timing of ascertainment of exposures and outcome.

CD = Crohn disease; NSAID = nonsteroidal anti-inflammatory drug; UC = ulcerative colitis.

Grahic Jump Location




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Posted on March 25, 2013
F. Hall Reynolds, MD
Chattanooga Skin and Cancer Clinic
Conflict of Interest: None Declared

Though now practicing Dermatology, this author first trained in Internal Medicine and was reading the March 2012 edition of the Annals of Internal Medicine when he noticed an article entitled “Aspirin, Nonsteroidal Anti-inflamatory Drug Use, and Risk for Crohn Disease and Ulcerative Colitis. A Cohort Study.” He wondered if it could help his debilitated assistant, a 42 year old female suffering from severe recurring attacks of abdominal pain and diarrhea for 4 years.

Of note, she began having joint pains 4 years before her GI symptoms and was taking ibuprofen for relief. Over the 4 years her joint pains increased which prompted her to take more ibuprofen, up to 1200 mg per day. Over the 4 years her GI symptoms were also increasing, especially the past year. Her GI symptoms consisted of debilitating episodes of crampy abdominal pain, watery diarrhea, fatigue, hypotensive episodes with near syncope, work loss, and depression, though her personal and family history were negative for GI disorders. She took carvedilol and had begun duloxetine for depressive symptoms. She went to her Family Practice doctor and the Emergency Room multiple times, saw three different gastroenterologists, underwent five CT scans, had 4 colonoscopies with multiple biopsies, was hospitalized for two prolonged stays, and was treated with repeated courses of antibiotics, corticosteroids, and narcotics for the consensus diagnosis of collagenous colitis.

After reading the article mentioned above, the author suggested his assistant read it. She did so and stopped taking ibuprofen, substituting acetaminophen for joint pains. Her GI symptoms lessened and soon totally disappeared. One year later she has had no further GI attacks or similar symptoms. She went from frequent work absence, near disability, and depression to a consistently present, hard working, cheerful member of our medical practice without anti-depressive medicine. Her working rheumatologic diagnosis is Sjogrens, and she has resumed her role of serving her family instead of being served. Her life was changed by reading this Journal. We hope sharing this experience will help someone else.

F.Hall Reynolds, MD

Debbie Visbal, CMA

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