Factors associated with resolution of ultrasound subclinical synovitis in anti-CCP-positive individuals with musculoskeletal symptoms: a UK prospective cohort study.

ABSTRACT

BACKGROUND: Subclinical synovitis occurs in a third of individuals at risk of rheumatoid arthritis. The objective of this study was to assess the reversibility of subclinical synovitis in individuals at risk of rheumatoid arthritis who are positive for anti-cyclic citrullinated peptide (CCP) antibody with musculoskeletal symptoms and investigate factors associated with its resolution within 12 months. METHODS: We conducted a single-centre, prospective, cohort study in the UK, recruiting individuals aged 18 years or older who were anti-CCP-positive with a new non-specific musculoskeletal symptom but no clinical synovitis. Referrals were made through primary or secondary care. Participants attended a baseline visit, which included a clinical assessment, blood tests, patient questionnaires, and a musculoskeletal ultrasound scan (ie, of wrists and metacarpophalangeal, proximal interphalangeal, and metatarsophalangeal joints), and then follow-up visits every 3 months for the first year, with a repeat ultrasound scan every 12 months. Participants with subclinical synovitis (ie, grey scale ≥1 and power Doppler ≥1) in at least one joint at baseline were selected for this analysis. Investigation of good prognostic factors by 12 months was done first using univariable analysis to identify significant factors in participants with no missing data. Then receiver operating characteristic (ROC) curves were used to establish the optimal cutoffs for significant continuous variables. Finally, a modified Poisson regression approach was performed to identify the best prediction model and was adjusted for confounders, using data from all participants, with missing values imputed. This study is registered with ClinicalTrials.gov, NCT02012764. FINDINGS: Between June 30, 2008, and Feb 24, 2020, 451 participants consented to participate in the CCP study and 122 (27%) individuals had subclinical synovitis at baseline, of whom 90 (74%) had data available at 12 months. Mean age was 54·1 years (SD 12·5), and 63 (70%) of 90 participants were women and 27 (30%) were men. Subclinical synovitis resolved in 43 (48%) of 90 participants, whereas subclinical synovitis persisted in 47 (52%) participants, 27 (57%) of whom developed clinical synovitis within 12 months. In the multivariable analysis, low anti-CCP titre (relative risk [RR] 1·52, 95% CI 1·04-2·22), negative rheumatoid factor (1·54, 0·92-2·58), subclinical synovitis in only one joint (1·62, 1·04-2·50), and an erythrocyte sedimentation rate of 15 mm/h or lower (1·82, 1·15-2·87) were predictors of subclinical synovitis resolution within 12 months (ie, good prognostic factors). ROC curve showed an area under the curve of 0·84 (95% CI 0·76-0·92; p<0·0001). Resolution occurred in seven (100%) of seven participants with all four factors present, and in only one (7%) of 14 participants with none of the factors present. INTERPRETATION: In individuals who were anti-CCP-positive, subclinical synovitis disappeared in approximately half of the participants by 12 months and was associated with the presence of good prognostic factors. Subclinical synovitis should be interpreted in the context of these additional factors. FUNDING: National Institute for Health Research Leeds Biomedical Research Centre.