Advanced therapies in US veterans with rheumatoid arthritis-associated interstitial lung disease: a retrospective, active-comparator, new-user, cohort study.

Summary

In a target-trial–emulated, propensity-matched VA cohort of RA-ILD patients, initiation of TNF inhibitors yielded similar risks of respiratory hospitalization, all-cause mortality, and respiratory mortality compared with non-TNF biologics/tsDMARDs. The findings argue against blanket avoidance of TNF inhibitors in RA-ILD.

Key Findings

• After propensity matching (n=237 vs 237), adjusted hazard ratio for the composite of death and respiratory hospitalization did not differ (aHR 1.21, 95% CI 0.92–1.58).
• No significant differences for respiratory hospitalization (aHR 1.27), all-cause mortality (aHR 1.15), or respiratory mortality (aHR 1.38) between TNF and non-TNF groups.
• Results were consistent across secondary, sensitivity, and subgroup analyses over up to 3 years of follow-up.

Clinical Implications

TNF inhibitors need not be categorically avoided in RA-ILD; selection can be individualized based on arthritis control, ILD severity, and comorbidities, pending comparative efficacy trials.

Limitations

• Observational design with potential residual confounding and selection bias.
• Population predominantly male US veterans, which may limit generalizability.

Future Directions

Conduct randomized or high-quality comparative effectiveness trials of TNF vs non-TNF agents in RA-ILD and evaluate outcomes across ILD patterns and fibrosis progression.