Is incident rheumatoid arthritis interstitial lung disease associated with methotrexate treatment? Results from a multivariate analysis in the ERAS and ERAN inception cohorts

Objectives To assess predictive factors for rheumatoid arthritis interstitial lung disease (RA-ILD) in two early RA inception cohorts with a focus on methotrexate (MTX) exposure. Design Multicenter prospective early RA inception cohort studies; the early RA study (ERAS) and the early RA network (ERAN) Setting Secondary care, ERAS 9 centers, ERAN 23 centers in England, Wales and the Republic of Ireland Participants Patients with new diagnosis of RA, n=2701.Standardised data including demographics, drug therapies and clinical outcomes including the presence of RA-ILD were collected at baseline, within 3- 6 months, at 12 months and annually thereafter. Primary and secondary outcome measures Primary outcome was the association of MTX exposure on RA-ILD diagnosis. Secondary outcomes were the association of demographic, comorbid and RA specific factors on RA-ILD diagnosis and the association of MTX exposure on time to RA-ILD diagnosis. Results Of 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 of RA-ILD cases only developing after any csDMARD treatment (n=67) showed MTX exposure not to be associated with incident RA-ILD (O.R. 0.85 CI 0.49, 1.49 p=0.578) and a non-significant trend for delayed ILD diagnosis (O.R. 0.54 CI 0.28, 1.06 p=0.072). In an extended analysis including RA-ILD cases present at RA diagnosis (n=92), MTX exposure was associated with a significantly reduced risk of incident RA-ILD (O.R. 0.48, CI 0.3, 0.79 p=0.004) and longer time to ILD diagnosis (O.R. 0.41, CI 0.23, 0.75 p=0.004). Other independent baseline associations with incident RA-ILD were higher age of RA onset, ever smoking, male gender, rheumatoid nodules and longer time from first RA symptom to first out-patient visit. Conclusions MTX treatment was not associated with an increased risk of RA-ILD diagnosis. On the contrary evidence suggested that MTX may delay the onset of ILD.