Cost-effective Tapering Algorithm in Patients with Rheumatoid Arthritis: Combination of Multibiomarker Disease Activity Score and Autoantibody Status

Melanie Hagen^{1

2}, Matthias Englbrecht^{1

2}, Judith Haschka^{1

2}, Michaela Reiser^{1

2}, Arnd Kleyer^{1

2}, Axel Hueber^{1

2}, Bernhard Manger^{1

2}, Camille Figueiredo^{1

2}, Jayme Fogagnolo Cobra^{1

2}, Hans-Peter Tony^{1

2}, Stephanie Finzel^{1

2}, Stefan Kleinert^{1

2}, Jörg Wendler^{1

2}, Florian Schuch^{1

2}, Monika Ronneberger^{1

2}, Martin Feuchtenberger^{1

2}, Martin Fleck^{1

2}, Karin Manger^{1

2}, Wolfgang Ochs^{1

2}, Hans-Martin Lorenz^{1

2}, Hubert Nüsslein^{1

2}, Rieke Alten^{1

2}, Jörg Henes^{1

2}, Klaus Krüger^{1

2}, Georg Schett^{1

2}, Jürgen Rech^{3

4}

Affiliations

¹ From the Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen, Erlangen, Germany; St. Vincent Hospital, Vinforce Study Group, Medical University of Vienna, Vienna, Austria; Institutio de Rheumatologia, São Paolo, Brazil; University of Würzburg, Internal Medicine 2, Würzburg; University Medical Center Freiburg, Rheumatology and Clinical Immunology, Freiburg; Rheumatology Clinical Practice Erlangen, Erlangen; Rheumatology Practice and Department of Internal Medicine 2, Clinic Burghausen, Burghausen; Asklepios Medical Center, Department of Rheumatology and clinical Immunology, Bad Abbach; Rheumatology Practice Bamberg, Bamberg; Rheumatology Practice Bayreuth, Bayreuth; University of Heidelberg, Medicine 5, Heidelberg; Rheumatology Practice Nuremberg, Nuremberg; Schlosspark Klinik, Internal Medicine/Rheumatology, Berlin; University of Tübingen, Centre for Interdisciplinary Clinical Immunology, Tübingen; Praxiszentrum St. Bonifatius, Munich, Germany.
² M. Hagen, BSc, CandMed, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; M. Englbrecht, PhD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; J. Haschka, MD, St. Vincent Hospital, Vinforce Study Group, Medical University of Vienna; M. Reiser, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; A. Kleyer, MD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; A. Hueber, MD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; B. Manger, MD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; C. Figueiredo, MD, Institutio de Rheumatologia; J. Fogagnolo Cobra, MD, Institutio de Rheumatologia; H.P. Tony, MD, University of Würzburg, Internal Medicine 2; S. Finzel, MD, University Medical Center Freiburg, Rheumatology and Clinical Immunology; S. Kleinert, MD, Rheumatology Clinical Practice Erlangen; J. Wendler, MD, Rheumatology Clinical Practice Erlangen; F. Schuch, MD, Rheumatology Clinical Practice Erlangen; M. Ronneberger, MD, Rheumatology Clinical Practice Erlangen; M. Feuchtenberger, MD, Rheumatology Practice and Department of Internal Medicine 2, Clinic Burghausen; M. Fleck, MD, Asklepios Medical Center, Department of Rheumatology and clinical Immunology; K. Manger, MD, Rheumatology Practice Bamberg; W. Ochs, MD, Rheumatology Practice Bayreuth; H.M. Lorenz, MD, University of Heidelberg, Medicine 5; H. Nüsslein, MD, Rheumatology Practice Nuremberg; R. Alten, MD, Schlosspark Klinik, Internal Medicine/Rheumatology; J. Henes, MD, University of Tübingen, Centre for Interdisciplinary Clinical Immunology; K. Krüger, MD, Praxiszentrum St. Bonifatius; G. Schett, MD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; J. Rech, MD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen.
³ From the Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen, Erlangen, Germany; St. Vincent Hospital, Vinforce Study Group, Medical University of Vienna, Vienna, Austria; Institutio de Rheumatologia, São Paolo, Brazil; University of Würzburg, Internal Medicine 2, Würzburg; University Medical Center Freiburg, Rheumatology and Clinical Immunology, Freiburg; Rheumatology Clinical Practice Erlangen, Erlangen; Rheumatology Practice and Department of Internal Medicine 2, Clinic Burghausen, Burghausen; Asklepios Medical Center, Department of Rheumatology and clinical Immunology, Bad Abbach; Rheumatology Practice Bamberg, Bamberg; Rheumatology Practice Bayreuth, Bayreuth; University of Heidelberg, Medicine 5, Heidelberg; Rheumatology Practice Nuremberg, Nuremberg; Schlosspark Klinik, Internal Medicine/Rheumatology, Berlin; University of Tübingen, Centre for Interdisciplinary Clinical Immunology, Tübingen; Praxiszentrum St. Bonifatius, Munich, Germany. juergen.rech@uk-erlangen.de.
⁴ M. Hagen, BSc, CandMed, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; M. Englbrecht, PhD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; J. Haschka, MD, St. Vincent Hospital, Vinforce Study Group, Medical University of Vienna; M. Reiser, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; A. Kleyer, MD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; A. Hueber, MD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; B. Manger, MD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; C. Figueiredo, MD, Institutio de Rheumatologia; J. Fogagnolo Cobra, MD, Institutio de Rheumatologia; H.P. Tony, MD, University of Würzburg, Internal Medicine 2; S. Finzel, MD, University Medical Center Freiburg, Rheumatology and Clinical Immunology; S. Kleinert, MD, Rheumatology Clinical Practice Erlangen; J. Wendler, MD, Rheumatology Clinical Practice Erlangen; F. Schuch, MD, Rheumatology Clinical Practice Erlangen; M. Ronneberger, MD, Rheumatology Clinical Practice Erlangen; M. Feuchtenberger, MD, Rheumatology Practice and Department of Internal Medicine 2, Clinic Burghausen; M. Fleck, MD, Asklepios Medical Center, Department of Rheumatology and clinical Immunology; K. Manger, MD, Rheumatology Practice Bamberg; W. Ochs, MD, Rheumatology Practice Bayreuth; H.M. Lorenz, MD, University of Heidelberg, Medicine 5; H. Nüsslein, MD, Rheumatology Practice Nuremberg; R. Alten, MD, Schlosspark Klinik, Internal Medicine/Rheumatology; J. Henes, MD, University of Tübingen, Centre for Interdisciplinary Clinical Immunology; K. Krüger, MD, Praxiszentrum St. Bonifatius; G. Schett, MD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; J. Rech, MD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen. juergen.rech@uk-erlangen.de.

PMID: 30504510
DOI: 10.3899/jrheum.180028

Clinical Trial

Cost-effective Tapering Algorithm in Patients with Rheumatoid Arthritis: Combination of Multibiomarker Disease Activity Score and Autoantibody Status

Melanie Hagen et al. J Rheumatol. 2019 May.

. 2019 May;46(5):460-466.

doi: 10.3899/jrheum.180028. Epub 2018 Dec 1.

Authors

Affiliations

¹ From the Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen, Erlangen, Germany; St. Vincent Hospital, Vinforce Study Group, Medical University of Vienna, Vienna, Austria; Institutio de Rheumatologia, São Paolo, Brazil; University of Würzburg, Internal Medicine 2, Würzburg; University Medical Center Freiburg, Rheumatology and Clinical Immunology, Freiburg; Rheumatology Clinical Practice Erlangen, Erlangen; Rheumatology Practice and Department of Internal Medicine 2, Clinic Burghausen, Burghausen; Asklepios Medical Center, Department of Rheumatology and clinical Immunology, Bad Abbach; Rheumatology Practice Bamberg, Bamberg; Rheumatology Practice Bayreuth, Bayreuth; University of Heidelberg, Medicine 5, Heidelberg; Rheumatology Practice Nuremberg, Nuremberg; Schlosspark Klinik, Internal Medicine/Rheumatology, Berlin; University of Tübingen, Centre for Interdisciplinary Clinical Immunology, Tübingen; Praxiszentrum St. Bonifatius, Munich, Germany.
² M. Hagen, BSc, CandMed, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; M. Englbrecht, PhD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; J. Haschka, MD, St. Vincent Hospital, Vinforce Study Group, Medical University of Vienna; M. Reiser, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; A. Kleyer, MD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; A. Hueber, MD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; B. Manger, MD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; C. Figueiredo, MD, Institutio de Rheumatologia; J. Fogagnolo Cobra, MD, Institutio de Rheumatologia; H.P. Tony, MD, University of Würzburg, Internal Medicine 2; S. Finzel, MD, University Medical Center Freiburg, Rheumatology and Clinical Immunology; S. Kleinert, MD, Rheumatology Clinical Practice Erlangen; J. Wendler, MD, Rheumatology Clinical Practice Erlangen; F. Schuch, MD, Rheumatology Clinical Practice Erlangen; M. Ronneberger, MD, Rheumatology Clinical Practice Erlangen; M. Feuchtenberger, MD, Rheumatology Practice and Department of Internal Medicine 2, Clinic Burghausen; M. Fleck, MD, Asklepios Medical Center, Department of Rheumatology and clinical Immunology; K. Manger, MD, Rheumatology Practice Bamberg; W. Ochs, MD, Rheumatology Practice Bayreuth; H.M. Lorenz, MD, University of Heidelberg, Medicine 5; H. Nüsslein, MD, Rheumatology Practice Nuremberg; R. Alten, MD, Schlosspark Klinik, Internal Medicine/Rheumatology; J. Henes, MD, University of Tübingen, Centre for Interdisciplinary Clinical Immunology; K. Krüger, MD, Praxiszentrum St. Bonifatius; G. Schett, MD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; J. Rech, MD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen.
³ From the Friedrich-Alexander-University Erlangen-Nuremberg (FAU), Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen, Erlangen, Germany; St. Vincent Hospital, Vinforce Study Group, Medical University of Vienna, Vienna, Austria; Institutio de Rheumatologia, São Paolo, Brazil; University of Würzburg, Internal Medicine 2, Würzburg; University Medical Center Freiburg, Rheumatology and Clinical Immunology, Freiburg; Rheumatology Clinical Practice Erlangen, Erlangen; Rheumatology Practice and Department of Internal Medicine 2, Clinic Burghausen, Burghausen; Asklepios Medical Center, Department of Rheumatology and clinical Immunology, Bad Abbach; Rheumatology Practice Bamberg, Bamberg; Rheumatology Practice Bayreuth, Bayreuth; University of Heidelberg, Medicine 5, Heidelberg; Rheumatology Practice Nuremberg, Nuremberg; Schlosspark Klinik, Internal Medicine/Rheumatology, Berlin; University of Tübingen, Centre for Interdisciplinary Clinical Immunology, Tübingen; Praxiszentrum St. Bonifatius, Munich, Germany. juergen.rech@uk-erlangen.de.
⁴ M. Hagen, BSc, CandMed, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; M. Englbrecht, PhD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; J. Haschka, MD, St. Vincent Hospital, Vinforce Study Group, Medical University of Vienna; M. Reiser, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; A. Kleyer, MD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; A. Hueber, MD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; B. Manger, MD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; C. Figueiredo, MD, Institutio de Rheumatologia; J. Fogagnolo Cobra, MD, Institutio de Rheumatologia; H.P. Tony, MD, University of Würzburg, Internal Medicine 2; S. Finzel, MD, University Medical Center Freiburg, Rheumatology and Clinical Immunology; S. Kleinert, MD, Rheumatology Clinical Practice Erlangen; J. Wendler, MD, Rheumatology Clinical Practice Erlangen; F. Schuch, MD, Rheumatology Clinical Practice Erlangen; M. Ronneberger, MD, Rheumatology Clinical Practice Erlangen; M. Feuchtenberger, MD, Rheumatology Practice and Department of Internal Medicine 2, Clinic Burghausen; M. Fleck, MD, Asklepios Medical Center, Department of Rheumatology and clinical Immunology; K. Manger, MD, Rheumatology Practice Bamberg; W. Ochs, MD, Rheumatology Practice Bayreuth; H.M. Lorenz, MD, University of Heidelberg, Medicine 5; H. Nüsslein, MD, Rheumatology Practice Nuremberg; R. Alten, MD, Schlosspark Klinik, Internal Medicine/Rheumatology; J. Henes, MD, University of Tübingen, Centre for Interdisciplinary Clinical Immunology; K. Krüger, MD, Praxiszentrum St. Bonifatius; G. Schett, MD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen; J. Rech, MD, FAU, Department of Internal Medicine 3 - Rheumatology and Immunology, Universitätsklinikum Erlangen. juergen.rech@uk-erlangen.de.

PMID: 30504510
DOI: 10.3899/jrheum.180028

Abstract

Objective: To analyze the effect of a risk-stratified disease-modifying antirheumatic drug (DMARD)-tapering algorithm based on multibiomarker disease activity (MBDA) score and anticitrullinated protein antibodies (ACPA) on direct treatment costs for patients with rheumatoid arthritis (RA) in sustained remission.

Methods: The study was a posthoc retrospective analysis of direct treatment costs for 146 patients with RA in sustained remission tapering and stopping DMARD treatment, in the prospective randomized RETRO study. MBDA scores and ACPA status were determined in baseline samples of patients continuing DMARD (arm 1), tapering their dose by 50% (arm 2), or stopping after tapering (arm 3). Patients were followed over 1 year, and direct treatment costs were evaluated every 3 months. MBDA and ACPA status were used as predictors creating a risk-stratified tapering algorithm based on relapse rates.

Results: RA patients with a low MBDA score (< 30 units) and negative ACPA showed the lowest relapse risk (19%), while double-positive patients showed high relapse risk (61%). In ACPA-negative and MBDA-negative (< 30 units), and ACPA or MBDA single-positive (> 30 units) groups, DMARD tapering appears feasible. Considering only patients without flare, direct costs for synthetic and biologic DMARD in the ACPA/MBDA-negative and single positive groups (n = 41) would have been €372,245.16 for full-dose treatment over 1 year. Tapering and stopping DMARD in this low-risk relapse group allowed a reduction of €219,712.03 of DMARD costs. Average reduction of DMARD costs per patient was €5358.83.

Conclusion: Combining MBDA score and ACPA status at baseline may allow risk stratification for successful DMARD tapering and cost-effective use of biologic DMARD in patients in deep remission as defined by the 28-joint count Disease Activity Score using erythrocyte sedimentation rate.

Keywords: ANTICYCLIC CITRULLINATED PROTEIN ANTIBODIES; DRUG COSTS; MULTIBIOMARKER DISEASE ACTIVITY; REMISSION; RHEUMATOID ARTHRITIS; TAPERING.

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Comment in

Value of the Multibiomarker Disease Activity Score to Predict Remission in RA: What Does the Evidence Show?
Fleischmann R. Fleischmann R. J Rheumatol. 2019 May;46(5):443-446. doi: 10.3899/jrheum.181061. J Rheumatol. 2019. PMID: 31043495 No abstract available.

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Cost-effective Tapering Algorithm in Patients with Rheumatoid Arthritis: Combination of Multibiomarker Disease Activity Score and Autoantibody Status

Affiliations

Cost-effective Tapering Algorithm in Patients with Rheumatoid Arthritis: Combination of Multibiomarker Disease Activity Score and Autoantibody Status

Authors

Affiliations

Abstract

Comment in

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Medical