Risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. A multicenter, case-control study. Methotrexate-Lung Study Group.

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 infinity]), 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.