C39-32 Does Rheumatoid Factor Reflect Pulmonary Vascular Risk in Rheumatoid Arthritis-associated Interstitial Lung Disease (RA-ILD)? A Real-world Multicenter Study

Abstract Introduction Rheumatoid arthritis (RA) is frequently complicated by interstitial lung disease (ILD) and pulmonary hypertension (PH), both major determinants of morbidity and mortality. High rheumatoid factor (RF) titers reflect a more aggressive immunologic phenotype and have been linked to fibrosing ILD and poor survival. However, the relationship between RF level and PH in RA-ILD remains uncertain. Prior studies were small and did not adequately control for ILD severity or treatment exposures. We aimed to determine whether high RF titers are independently associated with incident PH and all-cause mortality in patients with RA-ILD. Methods Using the TriNetX Research Network (2010-2024; 72 U.S. healthcare organizations), we identified adults with RA and ILD and classified them as Cohort 1 (High RF ≥ 60 IU/mL; n = 2193) and Cohort 2 (Low RF 60 IU/mL; n = 2585). Patients with pre-existing PH, left-heart disease, pulmonary embolism, lung transplantation, or other connective tissue diseases were excluded to isolate RA-related ILD. The index event was the first ILD diagnosis, with outcomes assessed ≥30 days later. Propensity-score matching (1:1, caliper 0.1) balanced age, sex, race, BMI, smoking, major comorbidities (COPD, CAD, CKD, DM, HTN), baseline oxygen use (proxy for ILD severity), and immunosuppressive therapy (methotrexate, biologics, glucocorticoids). After matching, 1 782 patients remained in each cohort (3 564 total) with all standardized mean differences 0.1. Primary outcomes were incident PH (ICD-10 I27.0, I27.2, I27.20, I27.23) and all-cause mortality. Secondary analysis restricted to type III PH ICD-10 I27.23 and R06.00. Kaplan-Meier and Cox models were used to estimate hazard ratios (HRs) with 95% confidence intervals. Results Before matching, high-RF patients were slightly older with greater comorbidity burden and higher oxygen use (p 0.05). After matching, covariates were balanced. Over a median follow-up of 3.7 years, PH occurred in 315 (29.3%) High RF vs 330 (33.1%) Low RF (HR 0.91, 95% CI 0.78-1.07; p = 0.24). In the secondary analysis (I27.23, R06.00), results were consistent (26 1.5% vs 20 1.1%; HR 1.35, 95% CI 0.75-2.42; p = 0.35). Mortality occurred in 451 (26.3%) vs 428 (24.9%) (HR 1.13, 95% CI 0.99-1.29; p = 0.07). Conclusion In this multicenter RA-ILD cohort, excluding other connective tissue diseases, high RF titers (≥60 IU/mL) were not associated with increased risk of PH but showed a non-significant trend toward higher all-cause mortality. Elevated RF may reflect systemic and fibrotic disease activity rather than pulmonary vascular remodeling in RA-ILD. This abstract is funded by: None