OBJECTIVES: This study aimed to investigate whether ultrasound (US)-detected features preceding Doppler-active synovitis are associated with progression to clinical arthritis in anticitrullinated protein antibody (ACPA)-positive individuals with musculoskeletal (MSK) symptoms. METHODS: In this prospective cohort study, 309 ACPA-positive individuals with MSK symptoms but without clinical arthritis and Doppler-active synovitis were included. US assessments evaluated minimal US findings, including synovial thickening, tendon sheath involvement, bursal effusions, and bone surface cortical irregularities. Longitudinal within-individual trajectories of US findings were analysed over time. Anticyclic citrullinated peptide 2 immunoglobulin G (IgG) and IgM rheumatoid factor (IgM RF) were measured at inclusion. The primary outcome was development of clinical arthritis over 3 years. Associations were analysed using Cox regression and logistic regression models. RESULTS: During a median follow-up of 13 months (IQR 7-22), 117 of 309 participants (38%) developed clinical arthritis, of whom 97 of 117 (83%) fulfilled the 2010 American College of Rheumatology/European League Against Rheumatism rhematoid arthritis classification criteria. Any US finding at baseline (75/309) was associated with a 3-fold increased risk of arthritis development (51/117 progressors vs 24/192 nonprogressors; hazard ratio HR 3.3, 95% CI 2.3-4.8). Among these, tendon sheath involvement showed the strongest association (HR 3.6, 95% CI 2.4-5.4), especially in combination with IgM RF positivity (HR 4.2, 95% CI 2.7-6.4). Longitudinal trajectories demonstrated progressive accumulation of US findings prior to arthritis onset, whereas such findings remained infrequent among nonprogressors. Tendon involvement frequently preceded synovial changes. CONCLUSIONS: Minimal US findings preceding Doppler-active synovitis, particularly tendon involvement, were strongly associated with progression to clinical arthritis in ACPA-positive individuals and support an US-identified 'presynovitis' phase of rheumatoid arthritis development and early risk stratification.
Kisten et al. (Sat,) studied this question.