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Risk Factors for Methotrexate-Induced Lung Injury in Patients with Rheumatoid Arthritis: A Multicenter, Case-Control Study

Graciela S. Alarcon, MD, MPH; Joel M. Kremer, MD; Maurizio Macaluso, MD, DrPH; Michael E. Weinblatt, MD; Grant W. Cannon, MD; William R. Palmer, MD; E. William St. Clair, MD; John S. Sundy, MD; Ronald W. Alexander, MS; G.J. Walker Smith, MD; and Constantine A. Axiotis, MD
[+] Article, Author, and Disclosure Information

For the Methotrexate-Lung Study Group From University of Alabama at Birmingham School of Medicine and University of Alabama at Birmingham School of Public Health, Birmingham, Alabama; Albany Medical College, Albany, New York; Harvard Medical School, Boston, Massachusetts; the Veterans Affairs Medical Center and University of Utah School of Medicine, Salt Lake City, Utah; Internal Medicine Associates, Omaha, Nebraska; Duke University Medical Center, Durham, North Carolina; Columbus Hospital, Great Falls, Montana; and Kings County Hospital, Brooklyn, New York. Acknowledgment: The authors thank Ella Henderson for expert secretarial assistance. Grant Support: In part by a grant from Lederle Laboratories, Pearl River, New Jersey, to Albany Medical College. Requests for Reprints: Graciela S. Alarcon, MD, MPH, University of Alabama at Birmingham Station-MEB 615, 1813 6th Avenue South, Birmingham, AL 35294. Current Author Addresses: Dr. Alarcon and Mr. Alexander: University of Alabama at Birmingham Station-MEB 615, 1813 6th Avenue South, Birmingham, AL 35294.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1997;127(5):356-364. doi:10.7326/0003-4819-127-5-199709010-00003
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Background: Toxicity limits the use of methotrexate.

Objective: To identify risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis.

Design: Case-control study.

Setting: One private and five academic rheumatology practices.

Participants: Methotrexate recipients with rheumatoid arthritis with and without lung injury.

Measurements: Potential risk factors examined were sociodemographic and lifestyle characteristics, medical history, clinical and ancillary features and treatment of rheumatoid arthritis before methotrexate therapy, and characteristics of methotrexate therapy. Cases of lung injury were defined according to the modified criteria of Searles and McKendry.

Results: Ninety-four percent of the study participants were white, and 67% were women. Case-patients (n = 29) were older than controls (n = 82) (61.5 compared with 54.5 years of age). The strongest predictors of lung injury, after adjustment for other variables, were older age (odds ratio [OR], 5.1 [95% CI, 1.2 to 21.1]), diabetes (OR, 35.6 [CI, 1.3 to ∞]), rheumatoid pleuropulmonary involvement (OR, 7.1 [CI, 1.1 to 45.4]), previous use of disease-modifying antirheumatic drugs (OR, 5.6 [CI, 1.2 to 27.0]), and hypoalbuminemia (OR, 19.5 [CI, 3.5 to 109.7]). Previous use of disease-modifying antirheumatic drugs and hypoalbuminemia had very large attributable risks.

Conclusion: Knowledge of the risk factors that predispose patients with rheumatoid arthritis to the toxic effects of methotrexate on the lung may provide a rationale for monitoring high-risk patients and may facilitate their management.





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