Risk of Serious Infection in Patients With Rheumatoid Arthritis–Associated Interstitial Lung Disease or Bronchiectasis: A Comparative Cohort Study

OBJECTIVE: To investigate the association between rheumatoid arthritis-associated lung disease (RA-LD) and serious infection risk. METHODS: We conducted a retrospective cohort study using the Massachusetts General Brigham Biobank (Boston, MA, USA), comparing RA-LD with patients with RA without lung disease (RA-no LD), matched by age, sex, and RA duration. Cases of RA-LD were verified by medical record review and chest imaging for clinically apparent RA-associated interstitial lung disease (RA-ILD) and/or RA-associated bronchiectasis (RA-BR). The primary outcome was serious infection. Incidence rates and propensity score-adjusted subdistribution hazard ratios (sdHRs) were calculated using Fine and Gray models to account for competing risk of death. RESULTS: Among 221 patients with RA-LD (151 RA-ILD and 70 RA-BR) and 980 RA-no LD comparators, RA-LD had a significantly higher serious infection risk compared with RA-no LD comparators (55.8 vs 25.8 per 1,000 person-years; sdHR 1.60; 95% confidence interval [CI] 1.20-2.12). The increased risk remained significant for those with RA-ILD (sdHR 1.79; 95% CI 1.33-2.41) but not for RA-BR (sdHR 1.19; 95% CI 0.72-1.97). Anatomic sites of infection that were more common in RA-LD included pulmonary, skin and soft tissue, and ear, nose, and throat; RA-LD was associated with various pathogen types, including virus, bacteria, fungus, and mycobacteria. Specific pathogens with higher frequency in cases of RA-LD, particularly among RA-BR, included influenza virus, respiratory syncytial virus, Staphylococcus, Pseudomonas, and nontuberculous mycobacteria. CONCLUSION: RA-LD, particularly RA-ILD, is associated with a significant increased risk of serious infection across anatomic sites and diverse pathogen types. RA-BR is associated with increased pulmonary infections. Prospective studies and trials are needed to clarify optimal approaches to treat patients with RA-LD and reduce infection risk.