title: EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update.
abstract: Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to-or adding-another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.
authors.affiliation: Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria.|2nd Department of Medicine, Hietzing Hospital, Vienna, Austria.
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
authors.affiliation: Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands.|Zuyderland Medical Center, Heerlen, The Netherlands.
authors.forename: Robert
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authors.lastname: Landewé
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Johannes
authors.initials: J
authors.lastname: Bijlsma
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Free University and Humboldt University Berlin, Berlin, Germany.
authors.forename: Gerd
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authors.lastname: Burmester
authors.affiliation: Rheumatology Department, Karolinska Institute, Stockholm, Sweden.
authors.forename: Katerina
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authors.affiliation: Rhumatologie B, Hopital Cochin, Paris, France.
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authors.affiliation: NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
authors.forename: Jackie
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authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Sofia
authors.identifier: http://orcid.org/0000-0002-8899-9087
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authors.affiliation: Department of Psychology, Health and Technology, University of Twente, Enschede, The Netherlands.
authors.forename: Marieke
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authors.lastname: Voshaar
authors.affiliation: Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands.|Zuyderland Medical Center, Heerlen, The Netherlands.
authors.forename: Ronald
authors.initials: R
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authors.affiliation: Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria.
authors.forename: Daniel
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authors.affiliation: Division of Rheumatology, Medizinische Klinik und Poliklinik III, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
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authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
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authors.initials: CD
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authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité-University Medicine Berlin, Free University and Humboldt University Berlin, Berlin, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Buttgereit
authors.affiliation: Department of Rheumatology, Hospital for Special Surgery, Weill Cornell Medical College, New York, New York, USA.|Rebecca McDonald Center for Arthritis & Autoimmune Disease, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Vivian
authors.initials: V
authors.lastname: Bykerk
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authors.forename: Mario
authors.identifier: http://orcid.org/0000-0002-2731-9180
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authors.affiliation: Rheumatology Department, Lapeyronie Hospital, Montpellier University, UMR 5535, Montpellier, France.
authors.forename: Bernard
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authors.lastname: Combe
authors.affiliation: Research Laboratory and Division of Clinical Rheumatology, University of Genoa, Genoa, Italy.
authors.forename: Maurizio
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authors.affiliation: Department of Patient & Care and Department of Rheumatology, University of Maastricht, Maastricht, The Netherlands.
authors.forename: Yvonne
authors.initials: Y
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authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Paul
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authors.affiliation: Division of Rheumatology, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: Axel
authors.initials: A
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authors.affiliation: Division of Rheumatology, University Hospitals of Geneva, Geneva, Switzerland.
authors.forename: Cem
authors.initials: C
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authors.affiliation: Fundación Ramón Dominguez, Hospital Clinico Universitario, Santiago, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Gomez-Reino
authors.affiliation: Department of Rheumatology, Sorbonne Universités, Pitié Salpêtrière Hospital, Paris, France.
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authors.affiliation: Institut de Biologie Moléculaire et Cellulaire, Immunopathologie, et Chimie Thérapeutique, Strasbourg University Hospital and University of Strasbourg, CNRS, Strasbourg, France.
authors.forename: Jacques-Eric
authors.initials: JE
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authors.affiliation: Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Johanna M W
authors.initials: JMW
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authors.affiliation: Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, University of Manchester, Manchester, UK.
authors.forename: Meghna
authors.identifier: http://orcid.org/0000-0002-1487-277X
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authors.forename: Dmitry
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authors.affiliation: European League Against Rheumatism, Zurich, Switzerland.|Cyprus League against Rheumatism, Nicosia, Cyprus.
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authors.affiliation: Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: Tore
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authors.affiliation: Department of Rheumatology and Immunology, Beijing University People's Hospital, Beijing, China.
authors.forename: Zhanguo
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authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris-Sud, Université Paris-Sud, INSERM U1184, Center for Immunology of viral Infections and Autoimmune Diseases (IMVA), Le Kremlin Bicêtre, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
authors.affiliation: Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Iain
authors.initials: I
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authors.affiliation: Organización Médica de Investigación, Buenos Aires, Argentina.
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authors.affiliation: Department of Rheumatology, Bernhoven, Uden, The Netherlands.
authors.forename: Piet
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authors.lastname: van Riel
authors.affiliation: University of Cologne, Cologne, Germany.
authors.forename: Andrea
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authors.lastname: Rubbert-Roth
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
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authors.identifier: http://orcid.org/0000-0002-2782-6780
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authors.forename: Tanja
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authors.lastname: Stamm
authors.affiliation: Keio University School of Medicine, Keio University Hospital, Tokyo, Japan.
authors.forename: Tsutomu
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authors.lastname: Takeuchi
authors.affiliation: Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium.|Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: René
authors.initials: R
authors.lastname: Westhovens
authors.affiliation: Department Medical Humanities, VU Medical Centre, Amsterdam, The Netherlands.
authors.forename: Maarten
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mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D008727:Methotrexate / Q000627:therapeutic use; D010358:Patient Participation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D005938:Glucocorticoids; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D053612:Janus Kinases; D008727:Methotrexate
keywords: DMARDs (biologic); DMARDs (synthetic); Disease Activity; Rheumatoid Arthritis; Treatment