A MULTI-BIOMARKER ALGORITHM FOR RA DISEASE ACTIVITY (VECTRA™ DA) PREDICTS RADIOGRAPHIC PROGRESSION IN THE BEST STUDY

Background: Identifying patients at greatest risk of radiographic progression is a key challenge in the management of RA. Since disease activity is associated with structural damage, it is important to understand the association of any new disease activity measure with risk of progression. Objectives: We set out to examine whether a multi-biomarker disease activity (MBDA) test for RA can also help predict progressive joint damage. We also evaluated the MBDA score's ability to track changes in disease activity in response to effective therapy. Methods: We analyzed 126 patients from the BeSt trial, which demonstrated the efficacy of early aggressive intervention in RA. The MBDA algorithm combines serum biomarkers (VCAM-1, EGF, VEGF-A, IL-6, TNF-RI, MMP-1, MMP-3, YKL-40, Leptin, Resistin, CRP, SAA) into a single score and is used in Vectra™ DA, a novel validated serum multi-biomarker disease activity test for RA which is commercially available in the US. Serum samples from baseline (BL) and year 1 were examined. Total Van der Heijde Sharp Scores (SHS) and DAS were available at BL, year 1, and year 2. The performance of the MBDA score and continuous clinical variables at BL or year 1 was evaluated by Spearman correlation to change in SHS over the next 12 months (ΔSHS) and by Area under the ROC curve (AUROC) for identifying joint damage progressors (ΔSHS>0). For binary clinical variables, C-indices (comparable to AUROC) were used. The MBDA score and other variables at year 1 (presence of erosions, CCP status, CRP, DAS28CRP, and 28 joint counts) were assessed as independent predictors of ΔSHS by multivariate ordinary least squares regression. For tracking disease activity, changes in median MBDA score from BL to year 1 were calculated and significance was assessed by Wilcoxon rank test. Results: Among individual continuous measures from year 1 assessed for their ability to predict ΔSHS, the MBDA score had the highest correlation with ΔSHS (ρ=0.34), followed by starting SHS (ρ=0.32), SJC28 (ρ=0.31), CRP (ρ=0.25), DAS28CRP (ρ=0.23), and TJC28 (ρ=0.1). Correlations of MBDA scores and other variables to 12-month ΔSHS were lower at BL than at year 1. The MBDA score at year 1 had the second highest performance at identifying joint damage progressors (AUROC =0.69) following SHS at 1 year (AUROC =0.77). In multivariate regression, only the MBDA score was a significant predictor of ΔSHS (p<0.05). Median MBDA scores dropped markedly from BL to year 1 (57 to 36, p<0.001). When change in disease activity was analyzed in each of the four study arms separately, the ranking of the arms was the same by MBDA score as by DAS28CRP. Conclusions: A pre-defined, multi-biomarker algorithm for RA disease activity can also predict joint damage progression, suggesting that the combination of biomarkers accurately reflects underlying disease processes. In addition to evaluating current disease activity, the MBDA score can track changes over time, and may complement clinical assessment for managing RA. Disclosure of Interest: C. Allaart Grant/Research support from: Scheringh-Plough, Centocor, Dutch College of Health Insurance, L. Dirven Grant/Research support from: Scheringh-Plough, Centocor, Dutch College of Health Insurance, S. Hirata: None Declared, P. Kerstens: None Declared, B. Dijkmans: None Declared, D. Chernoff Consultant for: Crescendo Bioscience, C Bio Aquinox, Lycera, Life Technologies, Schiff, Adamas, Tethys Bio, G. Cavet Employee of: Crescendo Bioscience, M. Centola Consultant for: Crescendo Bioscience, Employee of: OMRF, L. Hesterberg Employee of: Crescendo Bioscience, Y. Tanaka Consultant for: Mitsubishi Tanabe Pharma, Takeda Pharmaceutical Co Ltd, Abbott, Eisai Pharma, T. Huizinga Consultant for: Abbott Laboratories, Axis-Sheild, BMS, Novartis, Biotest AG, Crescendo Bioscience, Pfizer, Roche, Sanofi-aventis, Schering-Plough, Wyeth Pharmaceuticals, Speakers Bureau: Abbott Laboratories, Axis-Sheild, BMS, Novartis, Biotest AG, Roche, Sanofi-aventis, Wyeth Pharmaceuticals, Y. Shen Employee of: Crescendo BioscienceCitation: Annals of the Rheumatic Diseases, volume 70, supplement 3, year 2011, page 284Session: Rheumatoid arthritis – prognosis, predictors and outcome (Poster Presentations )