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Observational Study
. 2025 Dec 1;64(12):6079-6089.
doi: 10.1093/rheumatology/keaf315.

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

John Fitton  1   2 , Andrew Melville  1 , Andrea Di Matteo  1 , Jackie Nam  1   2 , Shouvik Dass  2 , Benazir Saleem  2 , Rudresh Shukla  3   4 , Paul Emery  1   5 , Richard J Wakefield  1   5 , Elizabeth M A Hensor  1   5 , Maya H Buch  3   4   5
Affiliations
Observational Study

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

John Fitton et al. Rheumatology (Oxford). .

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.

Keywords: DMARD; phenotypes; power Doppler; response; rheumatoid arthritis; synovitis; ultrasound.

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Figures

Figure 1.
Figure 1.
DAS28 component scores and ultrasound measures for each cluster. Box and whisker plots showing (A) DAS28 component scores and (B) individual ultrasound measures for each cluster (x-axis: 1–3). DAS28: disease activity score for 28 joints; E: enthesis; J: joint; GS: grey scale; PD: power Doppler; SJC: swollen joint count; T: tendon; TJC: tender joint count; VAS: visual analogue score
Figure 2.
Figure 2.
Median DAS28-CRP components over time for each cluster. Graphs showing median DAS28 components over 6 months for each cluster. (A) Observed data; (B) imputed data. C1: cluster 1; C2: cluster 2; C3: cluster 3; P1: cluster 1; P2: cluster 2; P3: cluster 3. SJC: swollen joint count; TJC: tender joint count; VAS: visual analogue score
Figure 3.
Figure 3.
Ultrasound scores at baseline and 6 months. Bar chart showing ultrasound scores by response status at 6 months for each of the combined clinical and ultrasound classes 1–3. (A) Class 1. Non-responder: n = 11; responder: n = 24. (B) Class 2. Non-responder: n = 9; responder: n = 29. (C) Class 3. Non-responder: n = 6; responder: n = 16. E: enthesis; J: joint; GS: grey scale; PD: power Doppler; T: tendon
Figure 3.
Figure 3.
Ultrasound scores at baseline and 6 months. Bar chart showing ultrasound scores by response status at 6 months for each of the combined clinical and ultrasound classes 1–3. (A) Class 1. Non-responder: n = 11; responder: n = 24. (B) Class 2. Non-responder: n = 9; responder: n = 29. (C) Class 3. Non-responder: n = 6; responder: n = 16. E: enthesis; J: joint; GS: grey scale; PD: power Doppler; T: tendon
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References

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