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EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update
  1. Josef S Smolen1,2,
  2. Robert Landewé3,4,
  3. Johannes Bijlsma5,
  4. Gerd Burmester6,
  5. Katerina Chatzidionysiou7,
  6. Maxime Dougados8,
  7. Jackie Nam9,
  8. Sofia Ramiro10,
  9. Marieke Voshaar11,
  10. Ronald van Vollenhoven3,4,
  11. Daniel Aletaha1,
  12. Martin Aringer12,
  13. Maarten Boers13,
  14. Chris D Buckley14,
  15. Frank Buttgereit6,
  16. Vivian Bykerk15,16,
  17. Mario Cardiel17,
  18. Bernard Combe18,
  19. Maurizio Cutolo19,
  20. Yvonne van Eijk-Hustings20,
  21. Paul Emery10,
  22. Axel Finckh21,
  23. Cem Gabay21,
  24. Juan Gomez-Reino22,
  25. Laure Gossec23,
  26. Jacques-Eric Gottenberg24,
  27. Johanna M W Hazes25,
  28. Tom Huizinga11,
  29. Meghna Jani26,
  30. Dmitry Karateev27,
  31. Marios Kouloumas28,29,
  32. Tore Kvien30,
  33. Zhanguo Li31,
  34. Xavier Mariette32,
  35. Iain McInnes33,
  36. Eduardo Mysler34,
  37. Peter Nash35,
  38. Karel Pavelka36,
  39. Gyula Poór37,
  40. Christophe Richez38,
  41. Piet van Riel39,
  42. Andrea Rubbert-Roth40,
  43. Kenneth Saag41,
  44. Jose da Silva42,
  45. Tanja Stamm43,
  46. Tsutomu Takeuchi44,
  47. René Westhovens45,46,
  48. Maarten de Wit47,
  49. Désirée van der Heijde10
  1. 1Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria
  2. 22nd Department of Medicine, Hietzing Hospital, Vienna, Austria
  3. 3Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands
  4. 4Zuyderland Medical Center, Heerlen, The Netherlands
  5. 5Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
  6. 6Department of Rheumatology and Clinical Immunology, Charité—University Medicine Berlin, Free University and Humboldt University Berlin, Berlin, Germany
  7. 7Rheumatology Department, Karolinska Institute, Stockholm, Sweden
  8. 8Rhumatologie B, Hopital Cochin, Paris, France
  9. 9NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust and Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK
  10. 10Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  11. 11Department of Psychology, Health and Technology, University of Twente, Enschede, The Netherlands
  12. 12Division of Rheumatology, Medizinische Klinik und Poliklinik III, Universitätsklinikum Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
  13. 13Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
  14. 14Birmingham NIHR Wellcome Trust Clinical Research Facility, Rheumatology Research Group, Institute of Inflammation and Ageing (IIA), University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK
  15. 15Department of Rheumatology, Hospital for Special Surgery, Weill Cornell Medical College, New York, New York, USA
  16. 16Rebecca McDonald Center for Arthritis & Autoimmune Disease, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
  17. 17Centro de Investigación Clínica de Morelia SC, Michoacán, México
  18. 18Rheumatology Department, Lapeyronie Hospital, Montpellier University, UMR 5535, Montpellier, France
  19. 19Research Laboratory and Division of Clinical Rheumatology, University of Genoa, Genoa, Italy
  20. 20Department of Patient & Care and Department of Rheumatology, University of Maastricht, Maastricht, The Netherlands
  21. 21Division of Rheumatology, University Hospitals of Geneva, Geneva, Switzerland
  22. 22Fundación Ramón Dominguez, Hospital Clinico Universitario, Santiago, Spain
  23. 23Department of Rheumatology, Sorbonne Universités, Pitié Salpêtrière Hospital, Paris, France
  24. 24Institut de Biologie Moléculaire et Cellulaire, Immunopathologie, et Chimie Thérapeutique, Strasbourg University Hospital and University of Strasbourg, CNRS, Strasbourg, France
  25. 25Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands
  26. 26Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, University of Manchester, Manchester, UK
  27. 27V.A. Nasonova Research Institute of Rheumatology, Moscow, Russian Federation
  28. 28European League Against Rheumatism, Zurich, Switzerland
  29. 29Cyprus League against Rheumatism, Nicosia, Cyprus
  30. 30Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
  31. 31Department of Rheumatology and Immunology, Beijing University People’s Hospital, Beijing, China
  32. 32Assistance 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
  33. 33Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
  34. 34Organización Médica de Investigación, Buenos Aires, Argentina
  35. 35Department of Medicine, University of Queensland, Queensland, Australia
  36. 36Institute of Rheumatology and Clinic of Rheumatology, Charles University, Prague, Czech Republic
  37. 37National Institute of Rheumatology and Physiotherapy, Semmelweis University, Budapest, Hungary
  38. 38Rheumatology Department, FHU ACRONIM, Pellegrin Hospital and UMR CNRS 5164, Bordeaux University, Bordeaux, France
  39. 39Department of Rheumatology, Bernhoven, Uden, The Netherlands
  40. 40University of Cologne, Cologne, Germany
  41. 41Division of Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA
  42. 42Serviço de Reumatologia, Centro Hospitalar e Universitário de Coimbra Praceta Mota Pinto, Coimbra, Portugal
  43. 43Section for Outcomes Research, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria
  44. 44Keio University School of Medicine, Keio University Hospital, Tokyo, Japan
  45. 45Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium
  46. 46Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium
  47. 47Department Medical Humanities, VU Medical Centre, Amsterdam, The Netherlands
  1. Correspondence to Professor Josef Smolen, Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Waehringer Guertel 18-20, Vienna A-1090, Austria; josef.smolen{at}wienkav.at, josef.smolen{at}meduniwien.ac.at

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.

  • Rheumatoid Arthritis
  • Treatment
  • DMARDs (synthetic)
  • DMARDs (biologic)
  • Disease Activity
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Footnotes

  • JSS and RL co-first authors. JSS and RL contributed equally.

  • Correction notice This article has been corrected since it published Online First. At the time of the online publication, baricitinib had received marketing authorisation in the EU; tofacitnib had already received a positive opinion but not yet marketing authorisation in the EU. This has now been obtained between online and print publication.

  • Twitter Follow Mario Cardiel @mhcardiel and Meghna Jani @MeghnaJani

  • Funding European League Against Rheumatism.

  • Competing interests A competing interests statement of all authors is attached as online supplementary material.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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