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People with rheumatoid arthritis have a significant risk of developing interstitial lung disease (RA-ILD), yet there is often a question as to whether methotrexate (MTX) exposure can cause or worsen ILD. A controlled cohort study suggests that MTX use is not associated with an increased risk of RA-ILD and instead, there is evidence suggesting MTX use may delay the onset of ILD.
RA patients from two early RA inception cohort studies ERAS, ERAN) in the UK, Wales and Ireland were assessed for ILD and their therapies. They found 92 eligible ILD cases; 39 occurred in 1578 (2.5%) MTX exposed and 53 in 1114 (4.8%) non-MTX exposed cases.
The primary analysis showed MTX exposure was not associated with incident RA-ILD (OR 0.85, 95% CI 0.49 to 1.49, p=0.578) and there was a non-significant trend for a delayed ILD diagnosis (OR 0.54, 95% CI 0.28 to 1.06, p=0.072).
Instead, MTX exposure was associated with a significantly reduced risk of incident RA-ILD (OR 0.48, 95% CI 0.3 to 0.79, p=0.004).
Other independent risk factors included baseline (higher) age of RA onset, ever smoking, male gender, rheumatoid nodules and longer time from first RA symptom to first outpatient visit.