RISK-FACTORS FOR METHOTREXATE-INDUCED LUNG INJURY IN PATIENTS WITH RHEUMATOID-ARTHRITIS - A MULTICENTER, CASE-CONTROL STUDY

Background: Toxicity limits the use of methotrexate. Objective: To ide ntify risk factors for methotrexate-induced lung injury in patients wi th rheumatoid arthritis. Design: Case-control study. Setting: One priv ate and five academic rheumatology practices. Participants: Methotrexa te recipients with rheumatoid arthritis with and without lung injury. Measurements: Potential risk factors examined were sociodemographic an d lifestyle characteristics, medical history, clinical and ancillary f eatures and treatment of rheumatoid arthritis before methotrexate ther apy, and characteristics of methotrexate therapy. Cases of lung injury were defined according to the modified criteria of Searles and McKend ry. 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 predicto rs of lung injury, after adjustment for other variables, were older ag e (odds ratio [OR], 5.1 [95% CI, 1.2 to 21.1]), diabetes (OR, 35.6 [CI , 1.3 to infinity]), rheumatoid pleuropulmonary involvement (OR, 7.1 [ CI, 1.1 to 45.4]), previous use of disease-modifying anti-rheumatic dr ugs (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 an d hypoalbuminemia had very large attributable risks. Conclusion: Knowl edge of the risk factors that predispose patients with rheumatoid arth ritis to the toxic effects of methotrexate on the lung may provide a r ationale for monitoring high-risk patients and may facilitate their ma nagement.