Early versus late onset interstitial lung disease in rheumatoid arthritis: An observational study of risk factors and mortality in Ontario, Canada

Abstract Background and Objective Interstitial lung disease (ILD) can occur as a manifestation of rheumatoid arthritis (RA) at various times in the disease course. We aimed to identify factors associated with early versus late onset RA‐ILD and how the timing of RA‐ILD influenced surgical lung biopsy completion and mortality. Methods We performed a retrospective observational study using health services data from Ontario, Canada. We identified RA cases between 2000 and 2020 using the Ontario Rheumatoid Arthritis Database. RA‐ILD diagnosis required repeat physician visits for ILD, with early RA‐ILD defined as within 1 year of RA diagnosis. We performed multivariable logistic regression to identify factors associated with early RA‐ILD and surgical lung biopsy completion, and multivariable cox‐proportional hazards regression to evaluate the association of early versus late RA‐ILD on all‐cause and RA‐ILD related mortality. Results In total, we identified 3717 cases of RA‐ILD. Older age at RA diagnosis [OR 1.04 (95%CI 1.03–1.05), p < 0.0001], female sex [OR 1.16 (95%CI 1.01–1.35), p = 0.04] and immigrating to Ontario [OR 1.70 (95%CI 1.35–2.14), p < 0.0001] was associated with early RA‐ILD. Patients with early versus late RA‐ILD experienced similar odds of undergoing a surgical lung biopsy [OR 1.34 (95%CI 0.83–2.16), p = 0.23]. Early RA‐ILD was associated with increased all‐cause mortality [HR 1.17 (95%CI 1.07–1.29), p = 0.0009], primarily driven by an increase in RA‐ILD related mortality [HR 1.45 (95%CI 1.19–1.76), p = 0.0003]. Conclusion Age at RA onset, female sex and immigration status are associated with early RA‐ILD. Patients with early RA‐ILD experience increased all‐cause and RA‐ILD related mortality after adjusting for demographics and comorbidities.