Performance of a multi-biomarker score measuring rheumatoid arthritis disease activity in the CAMERA tight control study.

Bakker MF, Cavet G, Jacobs JW, Bijlsma JW, Haney DJ, Shen Y, Hesterberg LK, Smith DR, Centola M, van Roon JA, Lafeber FP, Welsing PM.
Journal   Ann Rheum Dis.
Species  
Analytes Measured   Calprotectin , CRP , EGF , ICAM-1 , IL-6 , IL-6R , IL-8 , Leptin , MMP-1 , MMP-3 total , Resistin , SAA , TNF-RI , VCAM-1 , Flt-1 VEGFR1
Matrix Tested   Serum
Year   2012
Volume  
Page Numbers  
Application   Cytokines and Chemokines
Abstract
OBJECTIVES: To evaluate the performance of individual biomarkers and a multi-biomarker disease activity (MBDA) score in the early rheumatoid arthritis (RA) patient population from the computer assisted management in early rheumatoid arthritis (CAMERA) study.

METHODS: Twenty biomarkers were measured in the CAMERA cohort, in which patients were treated with either intensive or conventional methotrexate-based treatment strategies. The MBDA score was calculated using the concentrations of 12 biomarkers (SAA, IL-6, TNF-RI, VEGF-A, MMP-1, YKL-40, MMP-3, EGF, VCAM-1, leptin, resistin and CRP) according to a previously trained algorithm. The performance of the scores was evaluated relative to clinical disease activity assessments. Change in MBDA score over time was assessed by paired Wilcoxon rank sum test. Logistic regression was used to evaluate the ability of disease activity measures to predict radiographic progression.

RESULTS: The MBDA score had a significant correlation with the disease activity score based on 28 joints-C reactive protein (DAS28-CRP) (r=0.72; p<0.001) and an area under the receiver operating characteristic curve for distinguishing remission/low from moderate/high disease activity of 0.86 (p<0.001) using a DAS28-CRP cut-off of 2.7. In multivariate analysis the MBDA score, but not CRP, was an independent predictor of disease activity measures. Additionally, mean (SD) MBDA score decreased from 53 (18) at baseline to 39 (16) at 6 months in response to study therapy (p<0.0001). Neither MBDA score nor clinical variables were predictive of radiographic progression.

CONCLUSIONS: This multi-biomarker test performed well in the assessment of disease activity in RA patients in the CAMERA study. Upon further validation, this test could be used to complement currently available disease activity measures and improve patient care and outcomes.

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Multiplex
U-PLEX Custom Biomarker Group 1 (ms) 384-well Assays
6CKine/CCL21, BAFF, BCA-1/BLC, CD40/TNFRSF5, Eotaxin, EPO, GM-CSF, IFN-α, IFN-β, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17E/IL-25, IL-17F, IL-21, IL-22, IL-23, IL-27p28/IL-30, IL-31, IL-33, IP-10, KC/GRO, MCP-1, MCP-5/CCL12, MDC, MIP-1α, MIP-1β, MIP-2, MIP-3α, MMP-9 (total), NGAL/LCN2, RANTES, SDF-1α, TARC, TNF-α, TNF-RI, VEGF-A | Mouse
Multiplex
R-PLEX Mouse VEGFR-1/Flt-1 Antibody Set
VEGFR-1/Flt-1 | Mouse
R-PLEX Mouse VEGFR-1/Flt-1 Assay
VEGFR-1/Flt-1 | Mouse
Singleplex
U-PLEX Human Leptin 384-well Assay
Leptin | Human
Singleplex
U-PLEX Human IL-8 384-Well Assay
IL-8 | Human
Singleplex
U-PLEX Human IL-6 384-Well Assay
IL-6 | Human
Singleplex
U-PLEX Custom Metabolic Group 1 (human) 384-well Assays
BAFF, BDNF, β-NGF, C-Peptide, CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FGF-21, FGF-23, FLT3L, Fractalkine, FSH, G-CSF, Ghrelin (active), Ghrelin (total), GIP (active), GIP (inactive), GIP (total), GLP-1 (active), GLP-1 (inactive), GLP-1 (total), Glucagon, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, Insulin, IP-10, Leptin, Luteinizing Hormone (LH), MCP-1, MCP-2, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-5, PP, Proinsulin, PYY (total), SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 | Human
Multiplex
U-PLEX Custom Biomarker Group 1 (human) 384-well Assays
CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FLT3L, Fractalkine, G-CSF, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, IP-10, I-TAC, MCP-1, MCP-2, MCP-3, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-5, SDF-1α, TARC, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 | Human
Multiplex
R-PLEX Human Calprotectin Assay
Calprotectin | Human
Singleplex
R-PLEX Human Calprotectin Antibody Set
Calprotectin | Human
U-PLEX Human ICAM-1 Antibody Set
ICAM-1 | Human
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