Background/Purpose:

In early rheumatoid arthritis (eRA), predictors of radiographic damage would be useful for optimal targeting of therapy.  It has been suggested that combining various biomarkers may improve this prediction. The multi-biomarker disease activity (MBDA, Vectra DA) score has been validated as a measurement of rheumatoid arthritis (RA) disease activity. The MBDA score ranges from 1-100 and is based on 12 serum biomarkers: VCAM-1, EGF, VEGF-A, IL-6, TNF-RI, MMP-1, MMP-3, YKL-40, leptin, resistin, SAA and CRP.  In the SWEFOT study, 487 patients with eRA (symptom duration < 1 year) were started on methotrexate (MTX); at 3 months, responders (DAS28 < 3.2) continued MTX monotherapy and were followed in regular care, whereas non-responders were randomized to receive either triple DMARD therapy or the addition of infliximab.

The objective of this study was to assess the value of the baseline MBDA score as a predictor of radiographic progression over one year in eRA.

Methods: Analyses were performed for 235 patients from SWEFOT with baseline (BL), month 3 (n=220) and week 52 (n=235) assessments of DAS28, DAS28-CRP, CRP, MBDA score, and radiographs at BL and 1 year (using the Van der Heijde modified Sharp score [SHS]). Month 3 responders and non-responders were analyzed together.  Associations between disease activity indices and radiographic progression at one year were evaluated using Wald’s chi-square test.  Spearman’s correlation coefficients (r) were determined for the BL disease index scores versus radiographic progression (ΔSHS >5) over 1 year.

Results:

For the 235 patients, mean BL values were: CRP = 3.5 mg/dl, DAS28-ESR = 5.7, and MBDA = 60. More than half of patients with low CRP (≤ 1 mg/dL) or moderate DAS28 at BL had a high BL MBDA score (>44). Baseline SHS was 4.7 (median 2.0); mean ΔSHS from BL to 1 year was 3.1 ± 6.0 (median 1.0). Baseline MBDA score correlated with ΔSHS from BL to 1 year: r = 0.271 (p<0.001); correlations of DAS28, DAS28-CRP, and CRP with ΔSHS were weaker: r = 0.063, 0.014, and 0.178, respectively (p=NS, p=NS, p=0.006).  In bivariate analyses adjusting for DAS28 or CRP, MBDA had a significant additive value to prediction of radiographic progression at one year (p < 0.01).  Of the 43 patients with ΔSHS > 5, 98% had a high BL MBDA score, 77% a high DAS28 (>5.1) and 49% a high CRP (>3mg/dL). Of patients with a high MBDA score at BL, 21% had SHS progression >5, versus 3% and 0% for moderate and low MBDA, respectively (p<0.04). In patients with a high MBDA score at 3 months or 1 year, 24/96 (25%) and 13/40 (33%) progressed (ΔSHS > 5) from BL to 1 year, respectively.

Conclusion:

In eRA patients who were treated initially with MTX and then according to a step-up protocol, the MBDA score at baseline correlated significantly and independently from CRP or DAS28, with radiographic progression during the first year.  A high MBDA score at baseline was associated with a higher risk of radiographic progression, even in patients who had a low CRP or moderate DAS28 at baseline. Conversely, for patients with low or moderate MBDA at baseline the risk of radiographic progression was small. In untreated eRA, MBDA may help identify patients at low versus high risk of radiographic progression and thereby support rational treatment choices.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-multi-biomarker-disease-activity-score-correlates-with-radiographic-progression-in-early-rheumatoid-arthritis-results-from-a-randomized-trial/