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Consensus statement on blocking the effects of interleukin-6 and in particular by interleukin-6 receptor inhibition in rheumatoid arthritis and other inflammatory conditions
  1. Josef S Smolen1,2,
  2. Monika M Schoels2,
  3. Norihiro Nishimoto3,
  4. Ferdinand C Breedveld4,
  5. Gerd R Burmester5,
  6. Maxime Dougados6,
  7. Paul Emery7,
  8. Gianfranco Ferraccioli8,
  9. Cem Gabay9,
  10. Allan Gibofsky10,
  11. Juan Jesus Gomez-Reino11,
  12. Graeme Jones12,
  13. Tore K Kvien13,
  14. Miho Murakami3,
  15. Neil Betteridge14,
  16. Clifton O Bingham III15,
  17. Vivian Bykerk9,
  18. Ernest H Choy16,
  19. Bernard Combe17,
  20. Maurizio Cutolo18,
  21. Winfried Graninger19,
  22. Angel Lanas20,
  23. Emilio Martin-Mola21,
  24. Carlomaurizio Montecucco22,
  25. Mikkel Ostergaard23,
  26. Karel Pavelka24,
  27. Andrea Rubbert-Roth25,
  28. Naveed Sattar26,
  29. Marieke Scholte-Voshaar27,
  30. Yoshiya Tanaka28,
  31. Michael Trauner29,
  32. Gabriele Valentini30,
  33. Kevin L Winthrop31,
  34. Maarten de Wit32,
  35. Désirée van der Heijde4
  1. 1Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria
  2. 22nd Department of Medicine—Center for Rheumatic Disease, Hietzing Hospital, Vienna, Austria
  3. 3Laboratory of Immune Regulation, Wakayama Medical University, Wakayama, Japan
  4. 4Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  5. 5Department of Rheumatology and Clinical Immunology, Charité, Free University and Humboldt University, Berlin, Germany
  6. 6Department of Rheumatology, Cochin Hospital, René Descartes University, Paris, France
  7. 7Academic Unit of Musculoskeletal Diseases, Leeds University, Leeds, UK
  8. 8Division of Rheumatology and Internal Medicine—CIC, Catholic University of the Sacred Heart—School of Medicine, Rome, Italy
  9. 9Division of Rheumatology, University Hospital, University of Geneva, Geneva, Switzerland
  10. 10Hospital for Special Surgery, Weill Medical College of Cornell University, New York, New York, USA
  11. 11Hospital Clinic Universitario de Santiago, Santiago de Compostela, Spain
  12. 12Musculoskeletal Unit, Menzies Research Institute, University of Tasmania, Hobart, Australia
  13. 13Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
  14. 14Neil Betteridge Associates, London, UK
  15. 15Division of Rheumatology and Allergy and Clinical Immunology, Johns Hopkins University, Baltimore, Maryland, USA
  16. 16Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom
  17. 17Department of Rheumatology, University of Montpellier, Montpellier, France
  18. 18Division of Rheumatology, University of Genova, Genova, Italy
  19. 19Division of Rheumatology, Department of Medicine, Medical University of Graz, Graz, Austria
  20. 20Aragon Health Research Institute, University Hospital Lozano Blesa, University of Zaragoza School of Medicine, Zaragoza, Spain
  21. 21Servicio de Reumatología, Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, Spain
  22. 22Division of Rheumatology, Policlinico S. Matteo, University of Pavia, Pavia, Italy
  23. 23Department of Rheumatology, Copenhagen University Hospital at Glostrup, Copenhagen, Denmark
  24. 24Institute of Rheumatology and Clinics of Rheumatology, Charles University, Prague, Czech Republic
  25. 25Department of Internal Medicine I, University of Cologne, Cologne, Germany
  26. 26Glasgow Cardiovascular Research Center, University of Glasgow, Glasgow, UK
  27. 27EULAR Standing Committee of People with Arthritis/Rheumatism in Europe, Zurich, Switzerland
  28. 281st Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
  29. 29Division of Gastroenterology and Hepatology, Department of Medicine 3, Medical University of Vienna, Vienna, Austria
  30. 30 Department of Internal Medicine, University of Naples, Rheumatology Unit, Naples, Italy
  31. 31Division of Infectious Diseases, Oregon Health and Science University, Portland, Oregon, USA
  32. 32Department Medical Humanities, VU Medical Centre, Amsterdam, The Netherlands
  1. Correspondence to Professor Josef S Smolen, Division of Rheumatology, Department of Medicine 3, Medical University of Vienna, Waehringer Guertel 18–20, Vienna A-1090, Austria; josef.smolen{at}; josef.smolen{at}


Background Since approval of tocilizumab (TCZ) for treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), interleukin 6 (IL-6) pathway inhibition was evaluated in trials of TCZ and other agents targeting the IL-6 receptor and ligand in various RA populations and other inflammatory diseases. This consensus document informs on interference with the IL-6 pathway based on evidence and expert opinion.

Methods Preparation of this document involved international experts in RA treatment and RA patients. A systematic literature search was performed that focused on TCZ and other IL6-pathway inhibitors in RA and other diseases. Subsequently, incorporating available published evidence and expert opinion, the steering committee and a broader expert committee (both including RA patients) formulated the current consensus statement.

Results The consensus statement covers use of TCZ as combination- or monotherapy in various RA populations and includes clinical, functional and structural aspects. The statement also addresses the second approved indication in Europe JIA and non-approved indications. Also early phase trials involving additional agents that target the IL-6 receptor or IL-6 were evaluated. Safety concerns, including haematological, hepatic and metabolic issues as well as infections, are addressed likewise.

Conclusions The consensus statement identifies points to consider when using TCZ, regarding indications, contraindications, screening, dose, comedication, response evaluation and safety. The document is aimed at supporting clinicians and informing patients, administrators and payers on opportunities and limitations of IL-6 pathway inhibition.

  • Rheumatoid Arthritis
  • DMARDs (biologic)
  • Treatment

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