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Prediction of disease relapses by multibiomarker disease activity and autoantibody status in patients with rheumatoid arthritis on tapering DMARD treatment
  1. Juergen Rech1,
  2. Axel J Hueber1,
  3. Stephanie Finzel1,
  4. Matthias Englbrecht1,
  5. Judith Haschka1,2,
  6. Bernhard Manger1,
  7. Arnd Kleyer1,
  8. Michaela Reiser1,
  9. Jayme Fogagnolo Cobra3,
  10. Camille Figueiredo1,4,
  11. Hans-Peter Tony5,
  12. Stefan Kleinert5,6,
  13. Joerg Wendler6,
  14. Florian Schuch6,
  15. Monika Ronneberger6,
  16. Martin Feuchtenberger5,7,
  17. Martin Fleck8,
  18. Karin Manger9,
  19. Wolfgang Ochs10,
  20. Matthias Schmitt-Haendle10,
  21. Hanns-Martin Lorenz11,12,
  22. Hubert Nuesslein13,
  23. Rieke Alten14,
  24. Joerg Henes15,
  25. Klaus Krueger16,
  26. Georg Schett1
  1. 1Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany
  2. 2The Vinforce Study Group, Department of Internal Medicine 2, Saint Vincent Hospital, Vienna, Austria
  3. 3Instituto de Reumatologia de Sao Paulo, Sao Paulo, Brazil
  4. 4Division of Rheumatology, Universidade des Sao Paulo, Sao Paulo, Brazil
  5. 5Department of Internal Medicine 2, University of Wurzburg, Wurzburg, Germany
  6. 6Rheumatology Practice, Erlangen, Germany
  7. 7Rheumatology Practice and Department of Internal Medicine 2, Clinic Burghausen, Burghausen, Germany
  8. 8Department of Rheumatology and Clinical Immunology, Asklepios Medical Center, Bad Abbach, Germany
  9. 9Rheumatology Practice, Bamberg, Germany
  10. 10Rheumatology Practice, Bayreuth, Germany
  11. 11Division of Rheumatology, Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
  12. 12ACURA Center for Rheumatic Diseases, Baden-Baden, Germany
  13. 13Rheumatology Practice, Nuremberg, Germany
  14. 14Schlosspark Clinic, Berlin, Germany
  15. 15Department of Internal Medicine 2, University of Tubingen, Tubingen, Germany
  16. 16Rheumatology Practice, Munich, Germany
  1. Correspondence to Professor Georg Schett, Department of Internal Medicine 3, Rheumatology and Immunology, University Clinic of Erlangen-Nuremberg, Ulmenweg 18, Erlangen 91054, Germany; georg.schett{at}


Objective To analyse the role of multibiomarker disease activity (MBDA) score in predicting disease relapses in patients with rheumatoid arthritis (RA) in sustained remission who tapered disease modifying antirheumatic drug (DMARD) therapy in RETRO, a prospective randomised controlled trial.

Methods MBDA scores (scale 1–100) were determined based on 12 inflammation markers in baseline serum samples from 94 patients of the RETRO study. MBDA scores were compared between patients relapsing or remaining in remission when tapering DMARDs. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining predictors of relapse.

Results Moderate-to-high MBDA scores were found in 33% of patients with RA overall. Twice as many patients who relapsed (58%) had moderate/high MBDA compared with patients who remained in remission (21%). Baseline MBDA scores were significantly higher in patients with RA who were relapsing than those remaining in stable remission (N=94; p=0.0001) and those tapering/stopping (N=59; p=0.0001). Multivariate regression analysis identified MBDA scores as independent predictor for relapses in addition to anticitrullinated protein antibody (ACPA) status. Relapse rates were low (13%) in patients who were MBDA−/ACPA−, moderate in patients who were MBDA+/ACPA− (33.3%) and MBDA−ACPA+ (31.8%) and high in patients who were MBDA+/ACPA+ (76.4%).

Conclusions MBDA improved the prediction of relapses in patients with RA in stable remission undergoing DMARD tapering. If combined with ACPA testing, MBDA allowed prediction of relapse in more than 80% of the patients.

Trial registration number EudraCT 2009-015740-42.

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