Non-TNFi biologic and targeted synthetic DMARDs in rheumatoid arthritis-associated interstitial lung disease: A propensity score-matched, active-comparator, new-user study

Abstract

Objectives: This study aimed to compare treatment outcomes in rheumatoid arthritis-associated interstitial lung disease (RA-ILD) between initiators of rituximab, abatacept, tocilizumab, and tofacitinib using the Target Trial Emulation Framework.

Methods: We emulated three trials comparing abatacept, tocilizumab, and tofacitinib with rituximab (reference). Patients fulfilling validated RA-ILD algorithms initiating one of these non-TNFi b/tsDMARDs were propensity score (PS)-matched (1:1) using national Veterans Affairs (VA) data from 2006 to 2020. PS models included demographics, comorbidities, general health status indicators, and several RA- and ILD-related severity measures. Composite study outcomes were death and respiratory-related hospitalization, ascertained by VA data and linkages to the National Death Index and Medicare, over three-year (primary) and one-year follow-up periods (secondary). Cox regression models were used to analyze study outcomes adjusting for any unbalanced variables. Several sensitivity and subgroup analyses were performed.

Results: In the primary cohort, we 1:1 matched abatacept (n = 150), tocilizumab (n = 73), and tofacitinib (n = 94) with equal numbers of rituximab initiators (mean age 68.1-69.4 years, 88-92 % male). There were no significant differences in the primary composite outcome among any of the comparisons (abatacept aHR: 1.03 [0.72, 1.47]; tocilizumab aHR: 1.15 [0.68, 1.93]; tofacitinib aHR: 0.89 [0.54, 1.46]). Secondary, subgroup, and sensitivity analyses supported the main findings.

Conclusions: We did not find significant differences in mortality or respiratory hospitalization between RA-ILD patients initiating different non-TNFi b/tsDMARDs, though estimates were imprecise, and residual confounding may be present. These findings emphasize the need for clinical trials of advanced immunomodulatory therapies in RA-ILD.

Keywords: Biologics; Interstitial lung disease; Pharmacoepidemiology; Rheumatoid arthritis.