Clinical, Laboratory, and Treatment Characteristics of Seropositive and Seronegative Rheumatoid Arthritis: A Real-World Cohort Study

Seropositive and seronegative rheumatoid arthritis (RA) are increasingly recognized as clinically and biologically distinct disease subsets, yet comparative real-world data remain limited. We aimed to compare the sociodemographic, clinical, laboratory, and treatment characteristics of patients with seropositive and seronegative RA. This retrospective, single-center study included 559 patients with RA followed between September 2023 and May 2025. Seropositivity was defined as rheumatoid factor and/or anti-cyclic citrullinated peptide antibody (anti-CCP) positivity. Sociodemographic, clinical, laboratory, and treatment characteristics were compared between seropositive and seronegative patients. Of 559 patients, 446 (79.8%) were seropositive and 113 (20.2%) were seronegative. Disease duration was significantly longer in seropositive patients (p<0.001). At baseline, arthritis was more frequent in seronegative patients (p=0.019), whereas white blood cell count (WBC) and neutrophil counts were higher in seropositive patients (p=0.001 and p=0.006, respectively). Baseline C-reactive protein (CRP) levels did not differ between groups (p=0.261), whereas CRP levels at the last follow-up were higher in seropositive patients (p=0.035). CRP levels were significantly lower at the last follow-up than at baseline in both groups (p<0.001 for both). Biologic disease-modifying antirheumatic drug (bDMARD) use at the last follow-up was more frequent among seropositive patients (p=0.023). Seropositive and seronegative RA differed in several clinical, laboratory, and treatment characteristics. The higher frequency of baseline arthritis among seronegative patients supports recent evidence challenging the traditional view of seronegative RA as a uniformly milder form of the disease and highlights the clinical heterogeneity of RA according to serological status.