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

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.