• Open Access

Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity

Authors

  • Jeffrey R. Curtis,

    Corresponding author
    1. University of Alabama at Birmingham
    • UAB Center for Education and Research on Therapeutics, UAB Arthritis Clinical Intervention Program, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, FOT 805D, 510 20th Street South, Birmingham, AL 35294
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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.

  • Annette H. van der Helm-van Mil,

    1. Leiden University Medical Center, Leiden, The Netherlands
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  • Rachel Knevel,

    1. Leiden University Medical Center, Leiden, The Netherlands
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  • Tom W. Huizinga,

    1. Leiden University Medical Center, Leiden, The Netherlands
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    • Dr. Huizinga has received consultant fees (less than $10,000) from Crescendo Bioscience.

  • Douglas J. Haney,

    1. Crescendo Bioscience, South San Francisco, California
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    • Drs. Haney, Shen, Ramanujan, Chernoff, and Ford own stock and/or stock options in Crescendo Bioscience.

  • Yijing Shen,

    1. Crescendo Bioscience, South San Francisco, California
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    • Drs. Haney, Shen, Ramanujan, Chernoff, and Ford own stock and/or stock options in Crescendo Bioscience.

  • Saroja Ramanujan,

    1. Crescendo Bioscience, South San Francisco, California
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    • Drs. Haney, Shen, Ramanujan, Chernoff, and Ford own stock and/or stock options in Crescendo Bioscience.

  • Guy Cavet,

    1. Crescendo Bioscience, South San Francisco, California
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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.

  • Michael Centola,

    1. Oklahoma Medical Research Foundation, Oklahoma City
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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.

  • Lyndal K. Hesterberg,

    1. Crescendo Bioscience, South San Francisco, California
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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.

  • David Chernoff,

    1. Crescendo Bioscience, South San Francisco, California
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    • Drs. Haney, Shen, Ramanujan, Chernoff, and Ford own stock and/or stock options in Crescendo Bioscience.

  • Kerri Ford,

    1. Crescendo Bioscience, South San Francisco, California
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    • Drs. Haney, Shen, Ramanujan, Chernoff, and Ford own stock and/or stock options in Crescendo Bioscience.

  • Nancy A. Shadick,

    1. Brigham and Women's Hospital, Boston, Massachusetts
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    • Dr. Shadick has received grant support from Crescendo Bioscience, Biogen Idec, MedImmune, Abbott, Genentech, and Amgen.

  • Max Hamburger,

    1. Rheumatology Associates of Long Island, Melville, New York
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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.

  • Roy Fleischmann,

    1. University of Texas Southwestern Medical Center, Dallas
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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.

  • Edward Keystone,

    1. Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
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    • Dr. Keystone has received consultant fees (less than $10,000) from Crescendo Bioscience.

  • Michael E. Weinblatt

    1. Brigham and Women's Hospital, Boston, Massachusetts
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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.


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.

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