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Abstract Number: 2974

Multi-Biomarker Disease Activity Score Is Associated with Power Doppler Ultrasound in Patients with Rheumatoid Arthritis in Low Disease Activity State

Margaret H. Ma1, Toby Garrood2, Wanying Li3, Nadine A. Defranoux3, Gabrielle H. Kingsley4, Andrew P. Cope5 and David L. Scott6, 1King's College Hospital, London, United Kingdom, 2Rheumatology, Guy's and St. Thomas' Foundation Hospital NHS Trust, London, United Kingdom, 3Crescendo Bioscience Inc., South San Francisco, CA, 4Academic Rheumatology, Kings College London, London, United Kingdom, 5Academic Dept Rheumatology, King's College London, London, United Kingdom, 6King's College London, Department of Rheumatology, London, United Kingdom

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Biomarkers, remission, rheumatoid arthritis (RA) and ultrasound

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Session Information

Title: Rheumatoid Arthritis - Clinical Aspects VII: New Aspects of Monitoring Disease

Session Type: Abstract Submissions (ACR)

Background/Purpose: Rheumatoid arthritis (RA) patients increasingly achieve clinical remission with intensive treatment regimens. However, ultrasound (US) subclinical synovitis has been reported in remission states. The multi-biomarker disease activity (MBDA) blood test assesses overall RA disease activity.

The purpose of this study was to evaluate associations between US signals, MBDA score and its component biomarkers in the REMIRA cohort, a 1 year prospective observational study of patients with RA in low disease activity.

Methods: We studied 95 patients with RA on stable therapy for ≥6 months with DAS28 ≤3.2 for ≥1 month. Clinical measurements and serum samples were collected every 3 months for 1 year and US were conducted at baseline (BL) and 1 year. MBDA scores (range 1–100) were calculated from the serum concentrations of VCAM-1, EGF, VEGF-A, IL-6, TNF-RI, YKL-40, MMP-1, MMP-3, leptin, resistin, SAA and CRP using the validated Vectra® DA algorithm. MBDA disease activity thresholds have been defined as remission (<26), low (26-29), moderate (30-44), and high (>44). Power doppler (PD) and synovial hypertrophy (SH) of bilateral MCP joints and wrists were assessed by the same sonographer on the same machine and scored 0-3 for each joint and summed to provide total PD and SH scores (range 0-36). More stringent modified PD (mPD) and SH (mSH) scores were derived, based on MCP joint measures only, using signal thresholds determined from the distributions of BL PD and SH signals measured in a subset of patients who maintained no swollen joints (SJC28=0) without intensification of therapy over 1-year follow-up. Correlations between PD or SH and DAS28, MBDA scores or their components were evaluated by Spearman’s rank correlation.

 Results: Mean (±SD) BL disease activity measures were: DAS28 2.1 (±1.0), MBDA score 30 (±13), PD score 3.7 (±5.1), mPD 1.1 (±2.7), SH score 12.1 (±4.7), and mSH 0.4 (±1.1). At BL, 67% of patients were in DAS28 remission, 43% were in MBDA remission, 91% had PD>0 (31% had mPD>0) and 100% had SH>0 (21% had mSH>0). Statistically significant correlations (p<0.05) with PD and mPD were observed at both time points for MBDA scores (correlations ranged from 0.22-0.36), DAS28 (r=0.22-0.30), SJC28 (r=0.28-0.39), and four MBDA biomarker components: CRP (r=0.21-0.31), SAA (r=0.21-0.35), IL-6 (r= 0.26-0.39) and MMP-3 (r=0.24-0.36). The frequency of having MBDA score <26 was significantly greater in patients with mPD=0 than those with mPD>0 (52% vs. 24% at BL; 36% vs. 9% at 1 year). Correlations at BL or 1 year between SH or mSH and DAS28, MBDA score or components were weak or non-significant.

 Conclusion: Ultrasound PD and SH signals could be detected in most RA patients of the REMIRA cohort. After applying a modified, more stringent, scoring system, 21% to 31% had detectable US signals. We have shown, for the first time, significant correlations with PD and mPD scores for MBDA scores and some of its component biomarkers. Correlations were also found with DAS28 and SJC28. Remission by MBDA score was significantly associated with mPD=0. These results suggest that MBDA score detect low grade inflammation and subclinical synovitis in patients with RA in clinical remission or low disease activity.


Disclosure:

M. H. Ma,
None;

T. Garrood,
None;

W. Li,

Crescendo Bioscience, a fully own subsidiary of Myriad Genetics,

3;

N. A. Defranoux,

Crescendo Bioscience,

1,

Crescendo Bioscience,

3;

G. H. Kingsley,
None;

A. P. Cope,
None;

D. L. Scott,
None.

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