Diagnostic Performance of the Multi-Biomarker Disease Activity (MBDA) Score for Rheumatoid Arthritis in Patients with New-Onset Joint Symptoms: An Age-Stratified Retrospective Study

Purpose: Anti-citrullinated protein antibodies (ACPA) positivity decreases in elderly-onset rheumatoid arthritis (EORA), likely due to immunosenescence and clinical heterogeneity. This study aimed to evaluate the multi-biomarker disease activity (MBDA) score as an alternative diagnostic marker for rheumatoid arthritis (RA) in patients with new-onset joint symptoms, focusing on ACPA–negative cases stratified into young-onset RA (YORA) and EORA. Patients and Methods: This retrospective study was conducted at two institutions in Hokkaido, Japan (2018– 2022). Patients with new-onset joint symptoms who had not received prior RA therapy were included. Baseline serum samples were analyzed for MBDA and high-sensitivity C-reactive protein (hsCRP). Diagnostic performance for RA was evaluated using sensitivity, specificity, accuracy, area under the curve, and logistic regression. Results: Among 257 patients, 90 were < 60 years (RA, n = 42) and 167 were ≥ 60 years (RA, n = 84). In YORA, ACPA was the strongest predictor (odds ratio [OR]: 170.48, P < 0.01). In ACPA-negative YORA, both MBDA (OR: 6.51, P = 0.03) and hsCRP (OR: 15.56, P = 0.02) were significant, and their combination improved accuracy to 86.9% (OR: 18.00, P < 0.01). In EORA, ACPA showed lower accuracy (70.1%), whereas MBDA was higher (74.9%). In ACPA-negative EORA, the combination of MBDA and hsCRP provided the highest predictive ability (accuracy: 72.8%; OR: 43.52, P < 0.01). Conclusion: MBDA, particularly when combined with hsCRP, provides clinically meaningful diagnostic value for RA in patients with new-onset joint symptoms, particularly in ACPA-negative YORA and EORA. Trial Registration: This study was retrospectively registered in the University Hospital Medical Information Network (UMIN000057829). Keywords: Biomarkers, Early Diagnosis, Anti-Citrullinated Protein antibodies, Aged