Development and Validation of a New Disease Activity Score in 28 Joints–Based Treatment Response Criterion for Rheumatoid Arthritis

Authors

  • Frank Behrens,

    1. Johann Wolfgang Goethe University, Frankfurt am Main, Germany
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    • Dr. Behrens has received consultant fees and speaking fees (less than $10,000) from Abbott/AbbVie.

  • Hans-Peter Tony,

    1. University of Würzburg, Würzburg, Germany
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    • Dr. Tony has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Abbott and Roche.

  • Rieke Alten,

    1. Schlosspark-Klinik and Teaching Hospital Charite, University Medicine, Berlin, Germany
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    • Dr. Alten has received consultant fees, speaking fees, and/or honoraria (less than $10,000) from Abbott.

  • Stefan Kleinert,

    1. University of Würzburg, Würzburg, Germany
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    • Dr. Kleinert has received consultant fees, speaking fees, and/or honoraria (less than $10,000) from Abbott.

  • Eva C. Scharbatke,

    1. University of Würzburg, Würzburg, Germany
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    • Dr. Scharbatke has received consultant fees, speaking fees, and/or honoraria (less than $10,000) from Abbott.

  • Michaela Köhm,

    1. Johann Wolfgang Goethe University, Frankfurt am Main, Germany
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  • Holger Gnann,

    1. GKM Gesellschaft für Therapieforschung, Munich, Germany
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    • Dr. Gnann has received consultant fees (less than $10,000) from AbbVie.

  • Johanna Tams,

    1. ICRC-WEYER, Berlin, Germany
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    • Dr. Tams has received consultant fees (less than $10,000) from AbbVie.

  • Gerd Greger,

    1. AbbVie Deutschland, Wiesbaden, Germany
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    • Drs. Behrens and Tony and Drs. Greger and Burkhardt contributed equally to this work.

  • Harald Burkhardt

    Corresponding author
    • Johann Wolfgang Goethe University, Frankfurt am Main, Germany
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    • Dr. Burkhardt has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Abbott Germany and AbbVie Germany and (more than $10,000) from Abbott Germany.


Division of Rheumatology/CIRI, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, D 60590 Frankfurt/Main, Germany. E-mail: Harald.Burkhardt@kgu.de

Abstract

Objective

To define a valid criterion for treatment response as assessed by the Disease Activity Score in 28 joints (DAS28) that exceeds random disease activity variations in patients with rheumatoid arthritis (RA).

Methods

We utilized anonymized data sets of RA patients from multiple rheumatology centers in Germany to identify patients with stable responses to conventional or biologic disease-modifying antirheumatic drug (DMARD) therapy (discovery cohort). To evaluate fluctuations in DAS28 scores, we subjected patients' DAS28 scores at months 12, 18, and 24 to an analysis of variance model to establish a 1-sided 95% confidence interval for normal fluctuations; this value was used to define the critical difference (DAS28-dcrit) for individual changes from baseline. The DAS28-dcrit value was then applied to analyses of therapeutic response in an adalimumab noninterventional study cohort.

Results

The discovery cohort included 415 patients receiving stable treatment. Values for DAS28-dcrit were comparable regardless of age, sex, disease activity, and class of therapy (DMARDs or biologic agents) and fell below 1.8 in all subgroups. We therefore conclude that DAS28 improvements of 1.8 or higher are outside the normal variation and represent a therapeutic response. When applied to data from the adalimumab noninterventional study (n = 1,874), a DAS28-dcrit response was more robust over time than a European League Against Rheumatism response and was more closely correlated with improved functional capacity.

Conclusion

Based on our data, a DAS28-dcrit value of 1.8 signifies a positive individual therapeutic response that exceeds the threshold of random fluctuation. The DAS28-dcrit criterion may be useful in steering individual therapy and stratifying clinical trials.

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