Prediction of disease relapses by multibiomarker disease activity and autoantibody status in patients with rheumatoid arthritis on tapering DMARD treatment.
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.


BACKGROUND
EudraCT 2009-015740-42.
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
Juergen
J
Rech
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
Axel J
AJ
Hueber
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
Stephanie
S
Finzel
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
Matthias
M
Englbrecht
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany The Vinforce Study Group, Department of Internal Medicine 2, Saint Vincent Hospital, Vienna, Austria.
Judith
J
Haschka
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
Bernhard
B
Manger
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
Arnd
A
Kleyer
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
Michaela
M
Reiser
Instituto de Reumatologia de Sao Paulo, Sao Paulo, Brazil.
Jayme Fogagnolo
JF
Cobra
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany Division of Rheumatology, Universidade des Sao Paulo, Sao Paulo, Brazil.
Camille
C
Figueiredo
Department of Internal Medicine 2, University of Wurzburg, Wurzburg, Germany.
Hans-Peter
HP
Tony
Department of Internal Medicine 2, University of Wurzburg, Wurzburg, Germany Rheumatology Practice, Erlangen, Germany.
Stefan
S
Kleinert
Rheumatology Practice, Erlangen, Germany.
Joerg
J
Wendler
Rheumatology Practice, Erlangen, Germany.
Florian
F
Schuch
Rheumatology Practice, Erlangen, Germany.
Monika
M
Ronneberger
Department of Internal Medicine 2, University of Wurzburg, Wurzburg, Germany Rheumatology Practice and Department of Internal Medicine 2, Clinic Burghausen, Burghausen, Germany.
Martin
M
Feuchtenberger
Department of Rheumatology and Clinical Immunology, Asklepios Medical Center, Bad Abbach, Germany.
Martin
M
Fleck
Rheumatology Practice, Bamberg, Germany.
Karin
K
Manger
Rheumatology Practice, Bayreuth, Germany.
Wolfgang
W
Ochs
Rheumatology Practice, Bayreuth, Germany.
Matthias
M
Schmitt-Haendle
Division of Rheumatology, Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany ACURA Center for Rheumatic Diseases, Baden-Baden, Germany.
Hanns-Martin
HM
Lorenz
Rheumatology Practice, Nuremberg, Germany.
Hubert
H
Nuesslein
Schlosspark Clinic, Berlin, Germany.
Rieke
R
Alten
Department of Internal Medicine 2, University of Tubingen, Tubingen, Germany.
Joerg
J
Henes
Rheumatology Practice, Munich, Germany.
Klaus
K
Krueger
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
Georg
G
Schett
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D012720:Severity of Illness Index; D016896:Treatment Outcome
D018501:Antirheumatic Agents; D001323:Autoantibodies; D015415:Biomarkers; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide