Impact of Seropositivity on Mortality and Extra-Articular Manifestations in Rheumatoid Arthritis: A Nationwide Propensity-Matched Cohort Study

Abstract

Background/ Objective. Rheumatoid arthritis (RA) is a chronic autoimmune disease that manifests as either seropositive or seronegative subtypes. Seropositive RA is often linked to more severe joint damage and systemic complications. In contrast, seronegative RA has a less defined clinical profile but may still present with significant comorbidities. This study aims to compare clinical outcomes between these RA subtypes using real-world data from the TriNetX Research Network. Methods. A retrospective cohort study analysed adult RA patients from 2015 to 2025, categorised as seropositive or seronegative using International Classification of Diseases, 10th Revision (ICD-10 codes). The primary outcome was all-cause mortality, while secondary outcomes included hospitalization, steroid dependence, disease-modifying antirheumatic drug (DMARD) use, RA-related joint damage, interstitial lung disease (ILD), and coronary artery disease (CAD). Results. Among 106,492 matched patients (53,246 per cohort), seropositive RA patients had higher all-cause mortality (OR: 1.241; p < 0.001) and increased risks of DMARD use, steroid dependence, and joint damage. They also showed a greater incidence of ILD (OR: 2.419; p < 0.001), CAD indicating a more severe disease course. Conclusion. This study highlights significant differences in several clinical outcomes between seropositive and seronegative RA patients. These findings highlight the more aggressive nature of seropositive disease and its extra-articular involvement and reinforce the importance of autoantibody status in prognostication and risk stratification for RA patients.