Subclinical synovitis in arthralgia: how often does it result in clinical arthritis? Reflecting on starting points for disease-modifying anti-rheumatic drug treatment

Abstract

Objectives: According to guidelines, clinical arthritis is mandatory for diagnosing RA. However, in the absence of clinical synovitis, imaging-detected subclinical synovitis is increasingly used instead and is considered as a starting point for DMARD therapy. To search for evidence we studied the natural course of arthralgia patients with subclinical synovitis from three longitudinal cohorts and determined the frequencies of non-progression to clinically apparent inflammatory arthritis (IA) (i.e. 'false positives').

Methods: Subclinical synovitis in the hands or feet of arthralgia patients was visualized with US (two cohorts; definition: greyscale ≥2 and/or power Doppler ≥1) or MRI (one cohort; definition: synovitis score ≥1 by two readers). Patients were followed for 1 year on for IA development; two cohorts also had 3 year data. Analyses were stratified for ACPA.

Results: Subclinical synovitis at presentation was present in 36%, 41% and 31% in the three cohorts. Of the ACPA-positive arthralgia patients with subclinical synovitis, 54%, 44% and 68%, respectively, did not develop IA. These percentages were even higher in the ACPA-negative arthralgia patients: 66%, 85% and 89%, respectively. Similar results were seen after 3 years of follow-up.

Conclusion: Replacing clinical arthritis with subclinical synovitis to identify RA introduces a high false-positive rate (44-89%). These data suggest an overestimation regarding the value of ACPA positivity in combination with the presence of subclinical synovitis in patients with arthralgia, which harbours the risk of overtreatment if DMARDs are initiated in the absence of clinical arthritis.

Keywords: MRI; RA; anti-citrullinated antibodies (biomarkers); outcome assessment health care; ultrasonography.

Fig. 1

Percentage of progression and non-progression to inflammatory arthritis in arthralgia patients with subclinical synovitis at baseline (A) ACPA-positive patients (cohort 1, n = 37; cohort 2, n = 64; cohort 3, n = 90). Patients with subclinical synovitis at baseline (cohort 1, n = 13; cohort 2, n = 36; cohort 3, n = 31). Of these, 6, 20 and 10 patients, respectively, developed IA after 1 year of follow-up. ACPA-negative patients (cohort 1, n = 129; cohort 2, n = 409; cohort 3, n = 72). Patients with subclinical synovitis at baseline (cohort 1, n = 47; cohort 2, n = 157; cohort 3, n = 19). Of these 16, 23 and 2 patients, respectively, developed IA after 1 year of follow-up. (B) ACPA-positive patients (cohort 2, n = 43; cohort 3, n = 90). Patients with subclinical synovitis at baseline (cohort 2, n = 26; cohort 3, n = 31). Of these, 17 and 12 patients, respectively, developed IA after 3 years of follow-up. ACPA-negative patients (cohort 2, n = 292; cohort 3, n = 72). Patients with subclinical synovitis at baseline (cohort 2, n = 121; cohort 3, n = 19). Of these, 20 and 3 patients, respectively, developed IA after 3 years of follow-up.