Prediction of Disease Relapses By Multi-Biomarker Disease Test Activity in Rheumatoid Arthritis Patients Tapering DMARD Treatment

Juergen Rech¹, Axel J. Hueber², Matthias Englbrecht², Stephanie Finzel³, Judith Haschka^4,5, Bernhard Manger², Arnd Kleyer³, Michaela Reiser³, Hans-Peter Tony⁶, Stefan Kleinert⁷, Martin Feuchtenberger⁸, Martin Fleck⁹, Karin Manger¹⁰, Wolfgang Ochs¹¹, Matthias Schmitt-Haendle¹², Joerg Wendler¹³, Florian Schuch¹³, Monika Ronneberger¹³, Hanns-Martin Lorenz¹⁴, Hubert Nüßlein¹⁵, Rieke Alten¹⁶, Jayme Fogagnolo Cobra¹⁷, Joerg C. Henes¹⁸, Klaus Krüger¹⁹ and Georg A. Schett²⁰, ¹medical clinic 3, University of Erlangen-Nuremberg, Erlangen, Germany, ²Department of Internal Medicine 3, Rheumatology & Immunology, University of Erlangen-Nuremberg, Erlangen, Germany, ³Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany, ⁴Medical Department 3, Rheumatology & Immunology, University of Erlangen-Nuremberg, Erlangen, Germany, ⁵Medical Department II, Medical University of Vienna, St. Vincent Hospital Vienna,, Vienna, Austria, ⁶University Hospital Würzburg, Würzburg, Germany, ⁷Rheumatologische Schwerpunktpraxis Erlangen, Erlangen, Germany, ⁸Rheumatologie/Klinische Immunologie, Kreiskliniken Altötting-Burghausen, Burghausen, Germany, ⁹Department of Internal Medicine I, University of Regensburg, 93042 Regensburg, Germany, ¹⁰Rheumatology Practice Bamberg, Bamberg, Germany, ¹¹Rheumatologist in Private Practice, Bayreuth, Germany, ¹²Rheumatology Practice, Bayreuth, Germany, ¹³Schwerpunktpraxis Rheumatologie, Erlangen, Germany, ¹⁴University Hospital Heidelberg, Heidelberg, Germany, ¹⁵University Erlangen, Nürnberg, Germany, ¹⁶Internal Medicine, Rheumatology & Clinical Immunology, Schlosspark-Klinik, University Medicine Berlin, Berlin, Germany, ¹⁷Instituto de Reumatologia de Sao Paolo, Sao Paolo, Brazil, ¹⁸Department of Internal Medicine II, Rheumatology Division, University Hospital Tuebingen, Tuebingen, Germany, ¹⁹Praxiszentrum St. Bonifatius, München, Germany, ²⁰University of Erlangen-Nuremberg, Erlangen, Germany

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: ACPA, Biomarkers, DMARDs, remission and rheumatoid arthritis (RA)

Session Information

Date: Tuesday, November 10, 2015

Title: Rheumatoid Arthritis - Clinical Aspects Poster Session III

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: To analyze the role of multi-biomarker disease activity (MBDA) in predicting disease relapses in rheumatoid arthritis (RA) patients in sustained remission, tapering disease modifying anti-rheumatic drug (DMARD) therapy in a prospective randomized controlled trial.

Methods: Twelve individual inflammation markers were analyzed from baseline serum samples of 100 patients from the RETRO study by the standardized MBDA test (Vectra^® DA). MBDA scores range from 1-100 and are categorized as low (<30), moderate (30-44) or high (>44). The scores were calculated and compared between patients relapsing or remaining in remission when tapering DMARDs. Demographic and disease-specific parameters were recorded and included in multivariate logistic regression analysis for defining predictors of relapse.

Results: Moderate to high MBDA scores were found in 35% of RA patients, with doubling in patients relapsing (58.3%) than those remaining in stable remission (25%). Baseline MBDA scores were significantly higher in RA patients relapsing than those remaining in stable remission, when analyzing the entire population (N=100; p=0.0034), those tapering (N=36; p=0.0017) or stopping DMARDs (N=28; p=0.0036). Multivariate regression analysis identified MBDA scores as independent predictors for relapses next to anti-citrullinated protein antibody (ACPA) status. Relapse rates were low (13%) in MBDA-/ACPA- patients, moderate in MBDA+/ACPA- (33.3%) and ACPA+MBDA- (31.8%) patients and high in MBDA+/ACPA+ patients (76.4%). (Figure 1)

Conclusion: MBDA score improves the prediction of relapses in RA patients in stable remission undergoing DMARD tapering. If combined with ACPA testing, MBDA allows a correct case classification of relapse in more than 80% of the patients.

Figure 1. Relapse rates of RA dependent on ACPA and MBDA status: Kaplan-Meier curves indicate loss of remission over 12 months in patients with rheumatoid arthritis in relation to ACPA and MBDA status: (blue) ACPA/MBDA double-negative, (green) ACPA+/MBDA-, (yellow) ACPA-/MBDA+ and (purple) ACPA/MBDA double positive. Y-axis indicates the percentage of patients with rheumatoid arthritis in sustained remission (100% at baseline). X-axis indicates time.

Disclosure: J. Rech, None; A. J. Hueber, None; M. Englbrecht, None; S. Finzel, None; J. Haschka, None; B. Manger, None; A. Kleyer, None; M. Reiser, None; H. P. Tony, None; S. Kleinert, None; M. Feuchtenberger, None; M. Fleck, None; K. Manger, None; W. Ochs, None; M. Schmitt-Haendle, None; J. Wendler, None; F. Schuch, None; M. Ronneberger, None; H. M. Lorenz, None; H. Nüßlein, None; R. Alten, Horizon Pharma USA, Inc, 5,Horizon Pharma USA, Inc, 2; J. F. Cobra, None; J. C. Henes, None; K. Krüger, None; G. A. Schett, None.

To cite this abstract in AMA style:

Rech J, Hueber AJ, Englbrecht M, Finzel S, Haschka J, Manger B, Kleyer A, Reiser M, Tony HP, Kleinert S, Feuchtenberger M, Fleck M, Manger K, Ochs W, Schmitt-Haendle M, Wendler J, Schuch F, Ronneberger M, Lorenz HM, Nüßlein H, Alten R, Cobra JF, Henes JC, Krüger K, Schett GA. Prediction of Disease Relapses By Multi-Biomarker Disease Test Activity in Rheumatoid Arthritis Patients Tapering DMARD Treatment [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/prediction-of-disease-relapses-by-multi-biomarker-disease-test-activity-in-rheumatoid-arthritis-patients-tapering-dmard-treatment/. Accessed .

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