Clinical and epidemiological research by Pearson correlation (r). p Values for correlations were calcu- lated by permutation testing and adjusted for multiple hypoth- esis testing by calculating false discovery rate.31 The performance of the MBDA score algorithm was evalu- ated relative to clinical disease activity (DAS28-CRP) in three ways: (1) Pearson correlation (r). (2) Area under the receiver operating characteristic curve (AUROC) for discriminating between patients with moderate/high disease activity and those with remission/low disease activity (based on a DAS28- CRP cut-off of 2.7, the threshold separating remission/low disease activity from moderate/high disease activity for the DAS28-CRP; similar to the DAS28 threshold of 3.2).30 (3) The agreement between the classiﬁcation of disease activity (low, moderate and high disease activity) according to the MBDA score and according to DAS28-CRP was calculated using (weighted) κ. To determine whether CRP and the other MBDA biomark- ers were independently predictive of disease activity, the MBDA score was calculated with the CRP term omitted. Multivariate linear models with clinical disease activity measures (DAS28, DAS28-CRP and their components) as dependent variables were ﬁt by ordinary least squares regression. When using joint counts as dependent variables, the square roots of the counts were used (as in the DAS28 formula). The MBDA score and CRP (log transformed as in the DAS28 formula) were used as independent variables. Changes in MBDA scores between visits were assessed by paired Wilcoxon rank sum test. Prognostic value for progression of radiographic joint damage was assessed by logistic regression. Univariate logistic regres- sion analysis was performed with the MBDA score or DAS28- CRP as independent variable and progression in Sharp van der Figure 2. A-B. Performance of MBDA score relative to DAS28-CRP Figure 2A represents the Pearson correlation and AUROC for distinguishing remission/low from moderate/high DAS28-CRP. Figure 2B represents the ROC Curve for distinguishing remission/low DAS28-CRP from moderate/high DAS28-CRP. Table 1 Pearson correlations between individual biomarkers and clinical measures of disease activity DAS28-CRP Correlation 0.56 −0.04 0.69 −0.07 0.23 0.45 0.01 0.69 0.01 0.47 0.00 0.36 0.51 0.23 0.22 0.66 0.36 0.13 0.29 0.42 q Value <0.01 0.75 <0.01 0.46 0.02 <0.01 0.97 <0.01 0.97 <0.01 0.97 <0.01 <0.01 0.04 0.03 <0.01 <0.01 0.24 <0.01 <0.01 SJC28 Correlation 0.38 −0.13 0.41 −0.08 0.13 0.34 0.05 0.50 0.03 0.46 −0.07 0.29 0.40 0.29 0.13 0.43 0.30 0.14 0.18 0.35 q Value <0.01 0.19 <0.01 0.42 0.20 <0.01 0.58 <0.01 0.71 <0.01 0.53 <0.01 <0.01 <0.01 0.20 <0.01 <0.01 0.20 0.12 <0.01 TJC28 Correlation 0.33 −0.03 0.36 −0.12 0.08 0.31 −0.09 0.41 0.02 0.30 −0.06 0.19 0.26 0.21 0.13 0.37 0.24 0.08 0.07 0.30 q Value <0.01 0.73 <0.01 0.28 0.44 <0.01 0.44 <0.01 0.89 <0.01 0.56 0.06 <0.01 0.09 0.28 <0.01 0.02 0.56 0.56 <0.01 VAS-GH Correlation 0.25 0.01 0.32 0.02 0.09 0.27 −0.03 0.43 0.08 0.23 0.16 0.21 0.26 0.12 0.10 0.32 0.13 −0.03 0.14 0.15 q Value <0.01 0.94 <0.01 0.94 0.48 0.03 0.94 <0.01 0.53 0.03 0.18 0.05 0.05 0.39 0.43 <0.01 0.30 0.79 0.18 0.18 Correlations are shown for all biomarkers with DAS28-CRP and individual components. q Values reﬂect the false discovery rate and are calculated by adjusting the p values for multiple hypothesis testing. CCL22, C-C motif chemokine ligand 22; CRP, C reactive protein; DAS28-CRP, disease activity score based on 28 joints-CRP; EGF, epidermal growth factor; ICAM-1, inter-cellular adhesion molecule 1; IL, interleukin; IL-1B, IL-1 β; IL-1RA, IL-1 receptor antagonist; IL-6R, IL-6 receptor; MMP, matrix metallopeptidase; PYD, pyridinoline; SAA, serum amyloid A; SJC, swollen joint count; TJC, tender joint count; TNF-RI, tumour necrosis factor receptor type I; VAS-GH, visual analogue scale general health; VCAM-1, vascular cell adhesion molecule 1; VEGF-A, vascular endothelial growth factor A; YKL-40, cartilage glycoprotein 39. Ann Rheum Dis 2012;71:1692–1697. doi:10.1136/annrheumdis-2011-200963 Biomarker Calprotectin CCL22 CRP EGF ICAM-1 IL-1B IL-1RA IL-6 IL-6R IL-8 Leptin MMP-1 MMP-3 PYD Resistin SAA TNF-RI VCAM-1 VEGF-A YKL-40 1694 annrheumdis-2011-200963.indd 3 8/23/2012 3:34:17 AM