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. Trial registration number EudraCT 2009-015740-42.

[1]  H. Lorenz,et al.  Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stopping antirheumatic therapy: interim results from the prospective randomised controlled RETRO study , 2015, Annals of the rheumatic diseases.

[2]  P. Emery,et al.  Sustained remission with etanercept tapering in early rheumatoid arthritis. , 2014, The New England journal of medicine.

[3]  Yoshiya Tanaka,et al.  Discontinuation of adalimumab after achieving remission in patients with established rheumatoid arthritis: 1-year outcome of the HONOR study , 2013, Annals of the rheumatic diseases.

[4]  Inge Christoffer Olsen,et al.  Time trends in disease activity, response and remission rates in rheumatoid arthritis during the past decade: results from the NOR-DMARD study 2000–2010 , 2013, Annals of the rheumatic diseases.

[5]  C. Allaart,et al.  The BeSt way of withdrawing biologic agents. , 2013, Clinical and experimental rheumatology.

[6]  J. Carulli,et al.  Development of a Multi-Biomarker Disease Activity Test for Rheumatoid Arthritis , 2013, PloS one.

[7]  G. Cavet,et al.  Validation of a novel multibiomarker test to assess rheumatoid arthritis disease activity , 2012, Arthritis care & research.

[8]  G. Cavet,et al.  Performance of a multi-biomarker score measuring rheumatoid arthritis disease activity in the CAMERA tight control study , 2012, Annals of the rheumatic diseases.

[9]  M. Weinblatt,et al.  Sustained rheumatoid arthritis remission is uncommon in clinical practice , 2012, Arthritis Research & Therapy.

[10]  Andrew K. Brown,et al.  Synovitis and Osteitis Are Very Frequent in Rheumatoid Arthritis Clinical Remission: Results from an MRI Study of 294 Patients in Clinical Remission or Low Disease Activity State , 2011, The Journal of Rheumatology.

[11]  R. V. van Vollenhoven,et al.  When to initiate and discontinue biologic treatments for rheumatoid arthritis? , 2011, Journal of internal medicine.

[12]  B. Dijkmans,et al.  Drug-free remission: is it already possible? , 2011, Current opinion in rheumatology.

[13]  B. Dijkmans,et al.  Discontinuing treatment in patients with rheumatoid arthritis in sustained clinical remission: exploratory analyses from the BeSt study , 2010, Annals of the rheumatic diseases.

[14]  D. Symmons,et al.  2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. , 2010, Arthritis and rheumatism.

[15]  A. Silman,et al.  Rheumatoid arthritis classifi cation criteria : an American College of Rheumatology / European League Against Rheumatism collaborative initiative , 2010 .

[16]  Maurizio Cutolo,et al.  Treating rheumatoid arthritis to target: recommendations of an international task force , 2010, Annals of the rheumatic diseases.

[17]  D. M. van der Heijde,et al.  Prevalence of and predictive factors for sustained disease-modifying antirheumatic drug-free remission in rheumatoid arthritis: results from two large early arthritis cohorts. , 2009, Arthritis and rheumatism.

[18]  A. Richards,et al.  Withdrawal of disease-modifying antirheumatic drugs in patients with rheumatoid arthritis: a systematic review and meta-analysis , 2009, Annals of the rheumatic diseases.

[19]  C. Peterfy,et al.  An explanation for the apparent dissociation between clinical remission and continued structural deterioration in rheumatoid arthritis. , 2008, Arthritis and rheumatism.

[20]  B. Dijkmans,et al.  Drug-free remission, functioning and radiographic damage after 4 years of response-driven treatment in patients with recent-onset rheumatoid arthritis , 2008, Annals of the rheumatic diseases.

[21]  A. Koch The pathogenesis of rheumatoid arthritis. , 2007, American journal of orthopedics.

[22]  C. Peterfy,et al.  Presence of significant synovitis in rheumatoid arthritis patients with disease-modifying antirheumatic drug-induced clinical remission: evidence from an imaging study may explain structural progression. , 2006, Arthritis and rheumatism.

[23]  David T Felson,et al.  UvA-DARE (Digital Academic Repository) American College of Rheumatology/European League against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials , 2011 .

[24]  M. Prevoo,et al.  Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. , 1995, Arthritis and rheumatism.