Ultrasound-defined presynovitis is associated with progression to clinical arthritis in ACPA-positive individuals at risk of rheumatoid arthritis: longitudinal insights from the Karolinska Risk-RA cohort.

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.