Non-TNFi biologic and targeted synthetic DMARDs in rheumatoid arthritis-associated interstitial lung disease: A propensity score-matched, active-comparator, new-user study
Year: 2025
Type: article
Study design: Observational 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.
Institutions: University of Nebraska Medical Center, Philadelphia VA Medical Center, University of Pennsylvania, VA Nebraska Western Iowa Health Care System, VA Puget Sound Health Care System, University of Utah, VA Salt Lake City Healthcare System, University of Kansas Medical Center, University of Alabama at Birmingham, Omaha VA Medical Center
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,370
Funders: U.S. Department of Defense, U.S. Department of Veterans Affairs, Rheumatology Research Foundation, Health Services Research and Development, Biomedical Laboratory Research and Development, VA Office of Research and Development, National Institutes of Health, Rehabilitation Research and Development Service, Clinical Science Research and Development, National Institute of General Medical Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases
OpenAlex ID: W4409628378
