Judith Haschka1, Matthias Englbrecht2, Axel J Hueber2, Bernhard Manger2, Arnd Kleyer2, Michaela Reiser2, Stephanie Finzel2, Hans-Peter Tony3, Stefan Kleinert4, Martin Feuchtenberger5, Martin Fleck6, Karin Manger7, Wolfgang Ochs8, Matthias Schmitt-Haendle8, Joerg Wendler9, Florian Schuch9, Monika Ronneberger9, Hanns-Martin Lorenz10, Hubert Nuesslein11, Rieke Alten12, Winfried Demary13, Joerg Henes14, Georg Schett2, Juergen Rech2. 1. Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany Department of Internal Medicine 2, The Vinforce Study Group, Saint Vincent Hospital, Vienna, Austria. 2. Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany. 3. Department of Internal Medicine 2, University of Wurzburg, Wurzburg, Germany. 4. Department of Internal Medicine 2, University of Wurzburg, Wurzburg, Germany Rheumatology Practice, Erlangen, Germany. 5. Department of Internal Medicine 2, University of Wurzburg, Wurzburg, Germany Rheumatology Practice and Department of Internal Medicine 2, Clinic Burghausen, Burghausen, Germany. 6. Department of Rheumatology and Clinical Immunology, Asklepios Medical Center, Bad Abbach, Germany. 7. Rheumatology Practice, Bamberg, Germany. 8. Rheumatology Practice, Bayreuth, Germany. 9. Rheumatology Practice, Erlangen, Germany. 10. Department of Internal Medicine V, Division of Rheumatology, University of Heidelberg, Heidelberg, Germany ACURA Center for Rheumatic Diseases, Baden-Baden, Germany. 11. Rheumatology Practice, Nuremberg, Germany. 12. Schlosspark Clinic, Berlin, Germany. 13. Rheumatology Practice, Hildesheim, Germany. 14. Department of Internal Medicine 2, University of Tubingen, Tubingen, Germany.
Abstract
OBJECTIVE: To prospectively analyse the risk for disease relapses in patients with rheumatoid arthritis (RA) in sustained remission, either continuing, tapering or stopping disease-modifying antirheumatic drugs (DMARDs) in a prospective randomised controlled trial. METHODS: Reduction of Therapy in patients with Rheumatoid arthritis in Ongoing remission is a multicentre, randomised controlled, parallel-group phase 3 trial evaluating the effects of tapering and stopping all conventional and/or biological DMARDs in patients with RA in stable remission. Patients (disease activity score 28 (DAS28)<2.6 for least 6 months) were randomised into three arms, either continuing DMARDs (arm 1), tapering DMARDs by 50% (arm 2) or stopping DMARDs after 6 months tapering (arm 3). The primary endpoint was sustained remission during 12 months. RESULTS: In this interim analysis, the first 101 patients who completed the study were analysed. At baseline, all patients fulfilled DAS28 remission and 70% also American College of Rheumatology- European League Against Rheumatism Boolean remission. 82.2% of the patients received methotrexate, 40.6% biological DMARDs and 9.9% other DMARDs. Overall, 67 patients (66.3%) remained in remission for 12 months, whereas 34 patients (33.7%) relapsed. The incidence of relapses was related to study arms (p=0.007; arm 1: 15.8%; arm 2: 38.9%; arm 3: 51.9%). Multivariate logistic regression identified anticitrullinated protein antibodies (ACPA) positivity (p=0.038) and treatment reduction (in comparison to continuation) as predictors for relapse (arm 2: p=0.012; arm 3: p=0.003). CONCLUSIONS: This randomised controlled study testing three different treatment strategies in patients with RA in sustained remission demonstrated that more than half of the patients maintain in remission after tapering or stopping conventional and biological DMARD treatment. Relapses occurred particularly in the first 6 months after treatment reduction and were associated with the presence of ACPA. TRIAL REGISTRATION NUMBER: 2009-015740-42. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
RCT Entities:
OBJECTIVE: To prospectively analyse the risk for disease relapses in patients with rheumatoid arthritis (RA) in sustained remission, either continuing, tapering or stopping disease-modifying antirheumatic drugs (DMARDs) in a prospective randomised controlled trial. METHODS: Reduction of Therapy in patients with Rheumatoid arthritis in Ongoing remission is a multicentre, randomised controlled, parallel-group phase 3 trial evaluating the effects of tapering and stopping all conventional and/or biological DMARDs in patients with RA in stable remission. Patients (disease activity score 28 (DAS28)<2.6 for least 6 months) were randomised into three arms, either continuing DMARDs (arm 1), tapering DMARDs by 50% (arm 2) or stopping DMARDs after 6 months tapering (arm 3). The primary endpoint was sustained remission during 12 months. RESULTS: In this interim analysis, the first 101 patients who completed the study were analysed. At baseline, all patients fulfilled DAS28 remission and 70% also American College of Rheumatology- European League Against Rheumatism Boolean remission. 82.2% of the patients received methotrexate, 40.6% biological DMARDs and 9.9% other DMARDs. Overall, 67 patients (66.3%) remained in remission for 12 months, whereas 34 patients (33.7%) relapsed. The incidence of relapses was related to study arms (p=0.007; arm 1: 15.8%; arm 2: 38.9%; arm 3: 51.9%). Multivariate logistic regression identified anticitrullinated protein antibodies (ACPA) positivity (p=0.038) and treatment reduction (in comparison to continuation) as predictors for relapse (arm 2: p=0.012; arm 3: p=0.003). CONCLUSIONS: This randomised controlled study testing three different treatment strategies in patients with RA in sustained remission demonstrated that more than half of the patients maintain in remission after tapering or stopping conventional and biological DMARD treatment. Relapses occurred particularly in the first 6 months after treatment reduction and were associated with the presence of ACPA. TRIAL REGISTRATION NUMBER: 2009-015740-42. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Authors: Siri Lillegraven; Nina Paulshus Sundlisæter; Anna-Birgitte Aga; Joseph Sexton; Inge C Olsen; Hallvard Fremstad; Cristina Spada; Tor Magne Madland; Christian A Høili; Gunnstein Bakland; Åse Lexberg; Inger Johanne Widding Hansen; Inger Myrnes Hansen; Hilde Haukeland; Maud-Kristine Aga Ljoså; Ellen Moholt; Till Uhlig; Daniel H Solomon; Désirée van der Heijde; Tore K Kvien; Espen A Haavardsholm Journal: JAMA Date: 2021-05-04 Impact factor: 56.272