Dr. Curtis has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Pfizer, BMS, Crescendo Bioscience, and Abbott and (more than $10,000 each) from Roche/Genentech, UCB, Centocor, Amgen, and the Consortium of Rheumatology Researchers of North America (CORRONA), and has received research support from Amgen, UCB, CORRONA, Genentech, Centocor, Pfizer, and Crescendo Bioscience.
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Rheumatoid Arthritis
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Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity
Article first published online: 28 NOV 2012
DOI: 10.1002/acr.21767
Copyright © 2012 by the American College of Rheumatology
Additional Information
How to Cite
Curtis, J. R., van der Helm-van Mil, A. H., Knevel, R., Huizinga, T. W., Haney, D. J., Shen, Y., Ramanujan, S., Cavet, G., Centola, M., Hesterberg, L. K., Chernoff, D., Ford, K., Shadick, N. A., Hamburger, M., Fleischmann, R., Keystone, E. and Weinblatt, M. E. (2012), Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity. Arthritis Care Res, 64: 1794–1803. doi: 10.1002/acr.21767
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Dr. Curtis has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Pfizer, BMS, Crescendo Bioscience, and Abbott and (more than $10,000 each) from Roche/Genentech, UCB, Centocor, Amgen, and the Consortium of Rheumatology Researchers of North America (CORRONA), and has received research support from Amgen, UCB, CORRONA, Genentech, Centocor, Pfizer, and Crescendo Bioscience.
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Dr. Huizinga has received consultant fees (less than $10,000) from Crescendo Bioscience.
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Drs. Haney, Shen, Ramanujan, Chernoff, and Ford own stock and/or stock options in Crescendo Bioscience.
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Drs. Cavet, Centola, and Hesterberg own stock and/or stock options in Crescendo Bioscience and are inventors of the patent for Vectra DA.
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Dr. Shadick has received grant support from Crescendo Bioscience, Biogen Idec, MedImmune, Abbott, Genentech, and Amgen.
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Dr. Hamburger has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from UCB, Abbott, Novartis, URL, and Genentech and (more than $10,000 each) from Amgen, BMS, Human Genome Science, and GSK, owns stock and/or stock options in Human Genome Science, and has received research support from Abbott, Amgen, Bristol-Myers Squibb, Genentech, Human Genome Science, Pfizer, Chelsea, and Crescendo Bioscience.
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Dr. Fleischmann has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Abbott, Amgen, Centocor, Pfizer, Janssen, UCB, Roche, Lexicon, and Sanofi-Aventis.
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Dr. Keystone has received consultant fees (less than $10,000) from Crescendo Bioscience.
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Dr. Weinblatt has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Crescendo Bioscience, Biogen Idec, and MedImmune.
Publication History
- Issue published online: 28 NOV 2012
- Article first published online: 28 NOV 2012
- Accepted manuscript online: 26 JUN 2012 10:17AM EST
- Manuscript Accepted: 8 JUN 2012
- Manuscript Received: 24 JAN 2012
Funded by
- Crescendo Bioscience
- Biogen Idec
- NIH. Grant Numbers: AR053351, AR058964, AR058989, AR057133
- Agency for Healthcare Research and Quality. Grant Number: R01HS018517
Abstract
Objective
Quantitative assessment of disease activity in rheumatoid arthritis (RA) is important for patient management, and additional objective information may aid rheumatologists in clinical decision making. We validated a recently developed multibiomarker disease activity (MBDA) test relative to clinical disease activity in diverse RA cohorts.
Methods
Serum samples were obtained from the Index for Rheumatoid Arthritis Measurement, Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study, and Leiden Early Arthritis Clinic cohorts. Levels of 12 biomarkers were measured and combined according to a prespecified algorithm to generate the composite MBDA score. The relationship of the MBDA score to clinical disease activity was characterized separately in seropositive and seronegative patients using Pearson's correlations and the area under the receiver operating characteristic curve (AUROC) to discriminate between patients with low and moderate/high disease activity. Associations between changes in MBDA score and clinical responses 6–12 weeks after initiation of anti–tumor necrosis factor or methotrexate treatment were evaluated by the AUROC.
Results
The MBDA score was significantly associated with the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) in both seropositive (AUROC 0.77, P < 0.001) and seronegative (AUROC 0.70, P < 0.001) patients. In subgroups based on age, sex, body mass index, and treatment, the MBDA score was associated with the DAS28-CRP (P < 0.05) in all seropositive and most seronegative subgroups. Changes in the MBDA score at 6–12 weeks could discriminate both American College of Rheumatology criteria for 50% improvement responses (P = 0.03) and DAS28-CRP improvement (P = 0.002). Changes in the MBDA score at 2 weeks were also associated with subsequent DAS28-CRP response (P = 0.02).
Conclusion
Our findings establish the criterion and discriminant validity of a novel multibiomarker test as an objective measure of RA disease activity to aid in the management of RA in patients with this condition.