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

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.