Do Mechanisms Matter? Comparing Early Clinical and Ultrasound Responses to Advanced Therapies in Biologic-Naïve Rheumatoid Arthritis

Objectives Treatment response in rheumatoid arthritis (RA) varies considerably, even among biologic-naïve patients starting advanced therapies (ATs). Identifying whether early treatment effectiveness differs by mechanism of action could inform precision medicine strategies and optimize therapeutic selection. Ultrasound (US) is a sensitive, objective tool for assessing synovial inflammation, capable of detecting subclinical disease activity beyond clinical evaluation. This study compared early (3-month) clinical and US-assessed responses among biologic-naïve RA patients initiating different AT classes in a real-world setting. Methods At the ORCHESTRA (Ottawa Rheumatology CompreHEnSive TReatment and Assessment) Clinic, RA patients initiating a new biologic (bDMARD) or targeted synthetic DMARD (tsDMARD) underwent standardized baseline and 3-month follow-up evaluations, including clinical assessments and a comprehensive 36-joint US examination scored using the Global OMERACT-EULAR Synovitis Score (GLOESS). For this analysis, biologic-naïve patients with completed 3-month follow-up were categorized by treatment class: tumor necrosis factor inhibitors (TNFi), Janus kinase inhibitors (JAKi), and other biologics (rituximab, abatacept, or tocilizumab). Demographics, disease activity indices, and US synovitis scores were compared across groups at baseline and follow-up. Changes over time were analyzed to assess early treatment response. Results Eighty-six RA patients were included (69.8% female, mean age 55.4 years). Of these, 66 (76.7%) initiated TNFi, 11 (12.8%) JAKi, and 9 (10.5%) other biologics (rituximab: n=2; tocilizumab: n=3; abatacept: n=4). Baseline demographics and clinical features were similar, except that patients in the “other biologics” group were older and baseline deformities were more common among those initiating JAKi (Table). At baseline, disease activity scores and US findings were comparable between treatment groups. After 3 months, all groups demonstrated improvement in both clinical and US measures, with no significant between-group differences. The only observed difference was in the duration of morning stiffness (median: other biologics 0 [0–0] hours; JAKi 0.3 [0–0.5]; TNFi 0.3 [0–0.9]; p = 0.023), primarily driven by differences between TNFi and “other biologics.” Numerically more patients on JAKi’s (63.6%) achieved CDAI remission then TNFi’s (47%) and others (44%), although not reached statistical significance. Table-1: Comparison of sociodemographic characteristics, disease activity indices, and ultrasound scores among treatment groups in the RA cohort Conclusion In this real-world cohort of biologic-naïve RA patients, early (3-month) treatment responses assessed by both clinical and US measures were comparable across TNF inhibitors, JAK inhibitors, and other biologics. The findings suggest that short-term improvement in synovial inflammation is largely independent of treatment mechanism. Larger and longer-term studies are warranted to confirm these trends and identify predictors of differential therapeutic response.