Factors associated with gastrointestinal perforation in a cohort of patients with rheumatoid arthritis

Authors

  • Jeffrey R. Curtis,

    Corresponding author
    1. University of Alabama at Birmingham
    • UAB Center for Education and Research on Therapeutics, University of Alabama at Birmingham, FOT 805D, 510 20th Street South, Birmingham, AL 35294
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    • Dr. Curtis has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Pfizer, BMS, Crescendo, and Abbott, and (more than $10,000 each) from Roche/Genentech, UCB, Centocor, the Consortium of Rheumatology Researchers of North America, and Amgen.

  • Angel Lanas,

    1. Universidad de Zaragoza, Zaragoza, Spain
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    • Dr. Lanas has received consultant fees, speaking fees, and/ or honoraria (less than $10,000 each) from AstraZeneca, Roche/Genentech, Pfizer, and Bayer.

  • Ani John,

    1. Genentech, South San Francisco, California
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  • David A. Johnson,

    1. Eastern Virginia Medical School, Norfolk
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    • Dr. Johnson has received consultant fees, speaking fees, and/or honoraria (less than $10,000) from Roche/Genentech.

  • Kathy L. Schulman

    1. Outcomes Research Solutions, Inc., Bolton, Massachusetts
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    • Ms Schulman is an employee of Outcomes Research Solutions, Inc., which received consultant fees, speaking fees, and/or honoraria (more than $10,000) from Roche/Genentech.


Abstract

Objective

To estimate the incidence and risk factors for gastrointestinal (GI) perforation among patients with rheumatoid arthritis (RA).

Methods

Claims from employer health insurance plans were used to identify RA patients and those hospitalized for upper or lower GI perforation. GI perforation cases were identified using both a sensitive and a specific definition. A Cox model using fixed and time-varying covariates was used to evaluate the risk of GI perforation.

Results

Among 143,433 RA patients, and using a maximally sensitive GI perforation definition, 696 hospitalizations with perforation were identified. The rate of perforation was 1.70 per 1,000 person years (PYs; 95% confidence interval [95% CI] 1.58–1.83), and most perforations (83%) occurred in the lower GI tract. The rate of perforation was lower when a more specific GI perforation definition was used (0.87; 95% CI 0.78–0.96 per 1,000 PYs). Age and diverticulitis were among the strongest risk factors for perforation (diverticulitis hazard ratio [HR] 14.5 [95% CI 11.8–17.7] for the more sensitive definition, HR 3.9 [95% CI 2.5–5.9] for the more specific definition). Among various RA medication groups and compared to methotrexate, the risk of GI perforation was highest among patients with exposure to nonsteroidal antiinflammatory drugs (NSAIDs), concomitant nonbiologic disease-modifying antirheumatic drugs, and glucocorticoids. Biologic agents without glucocorticoid exposure were not a risk factor for perforation.

Conclusion

GI perforation is a rare but serious condition that affects patients with RA, most frequently in the lower GI tract. Clinicians should be aware of risk factors for GI perforation when managing RA patients, including age, history of diverticulitis, and use of glucocorticoids or NSAIDs.

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