Neither ultrasound synovitis nor clinical-ultrasound phenotypes of established rheumatoid arthritis predict response to targeted therapy

OBJECTIVES: To identify patient sub-phenotypes using clinical and imaging measures in established rheumatoid arthritis (RA) and to establish if baseline ultrasound synovitis and/or baseline patient sub-phenotypes predicts response to targeted therapy (TT).

METHODS: An observational cohort study of consecutively recruited patients with established RA starting TT. Participants received clinical assessment, 38-joint musculoskeletal ultrasound (MSUS), measuring grey scale (GS) and power doppler (PD) synovitis/tenosynovitis, and patient reported outcomes (PRO), prior to and 6 months after treatment. Latent profile analysis of the clinical and MSUS variables identified disease clusters and multinomial logistic regression models determined whether these and/or baseline synovitis predicted EULAR response.

RESULTS: Of 200 recruited patients, 3 clusters, low to high inflammatory, were identified with median (IQR) total joint PD 2 (0-4) in cluster one, 9 (6-13) in cluster two and 29.5 (21-45) in cluster three. Health assessment questionnaire correlated with disease activity, DAS-P score distributions differed between clusters (p= 0.001) but with identical medians. Other PROs did not differ. At 6 months relative risk ratio (RRR) of EULAR response in those with baseline synovitis compared with those without was 1.05 (95% CI 0.38, 2.93) and response compared with the lowest inflammatory cluster (1) was 1.50 (95% CI 0.61, 3.70) for cluster 2 and 1.24 (95%CI 0.43, 3.60) for cluster 3.

CONCLUSION: This is the first study to identify RA phenotypes employing 38-joint MSUS. Strikingly, neither baseline synovitis nor inflammatory cluster predicted clinical response. Mechanistic understanding of TT response/non-response is needed and clinical trials need to still capture all these populations.