Antinuclear Antibodies Predict Treatment Escalation and Biologic Switching in Rheumatoid Arthritis

Background: Antinuclear antibodies (ANAs) are frequently detected in patients with rheumatoid arthritis (RA); however, their prognostic relevance in predicting treatment escalation remains uncertain. Identifying biomarkers associated with earlier transition to advanced therapies may improve individualized disease management. Objectives: To evaluate the association of ANA status and titer levels with clinical characteristics, treatment trajectories, and time to biologic therapy initiation in patients with RA. Methods: In this retrospective cohort study, 223 patients with RA were stratified ac-cording to ANA status (112 ANA-positive, 111 ANA-negative). Baseline demographic data, disease activity (DAS28), and serological markers (RF, anti-CCP) were analyzed. Time to biologic therapy initiation, defined from the date of RA diagnosis to first bio-logic or targeted synthetic DMARD use, was assessed using Kaplan–Meier survival analysis and Cox proportional hazards regression. Multivariate models adjusted for relevant clinical covariates. Within the ANA-positive group, exploratory analyses compared low–moderate (1:80–1:320) and high (>1:320) ANA titers. Results: Baseline demographic and clinical characteristics were comparable between groups (all p > 0.05). ANA-positive patients more frequently initiated biologic therapy (48.2% vs. 24.3%, p < 0.001) and underwent multiple biologic switches (29.5% vs. 16.2%, p = 0.028). In multivariate analysis, ANA positivity was independently associated with earlier bi-ologic initiation (adjusted HR 2.14; 95% CI 1.32–3.46; p = 0.002), whereas RF and an-ti-CCP status were not significant predictors. In exploratory subgroup analysis, high ANA titers (>1:320) were associated with a lower hazard of biologic initiation com-pared with low–moderate titers (HR 0.24; 95% CI 0.06–0.98; p = 0.048). Conclusions: ANA positivity was independently associated with earlier initiation of biologic therapy in RA, supporting its potential incremental prognostic value beyond traditional sero-logical markers. The observed non-linear association between ANA titers and treat-ment escalation warrants cautious interpretation and validation in prospective studies.