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

Fitton, J.; Melville, A.; Di Matteo, A.; Nam, J.; Dass, S.; Saleem, B.; Shukla, R.; Emery, P.; Wakefield, RJ.; Hensor, EMA.; Buch, MH.

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

All Authors

Fitton, J.

Melville, A.

Di Matteo, A.

Nam, J.

Dass, S.

Saleem, B.

Shukla, R.

Emery, P.

Wakefield, RJ.

Hensor, EMA.

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LTHT Author

Di Matteo, Andrea
Nam, Jacqueline
Dass, Shouvik
Saleem, Benazir
Emery, Paul
Wakefield, Richard
Hensor, Elizabeth

LTHT Department

NIHR Leeds Biomedical Research Centre
Rheumatology

Publication Date

2025

Item Type

Journal Article
Observational Study

Abstract

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: This was 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 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, three clusters, low to high inflammatory, were identified with median (IQR) total joint PD 2 (0-4) in cluster 1, 9 (6-13) in cluster 2 and 29.5 (21-45) in cluster 3. A health assessment questionnaire correlated with disease activity, and 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 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.