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Clinical trials of new drugs for the treatment of rheumatoid arthritis: focus on early disease
  1. Josef S Smolen1,2,
  2. Sabine Collaud Basset3,
  3. Maarten Boers4,5,
  4. Ferdinand Breedveld6,
  5. Christopher J Edwards7,
  6. Tore K Kvien8,
  7. Pierre Miossec9,
  8. Tuulikki Sokka-Isler10,
  9. Ronald F van Vollenhoven5,11,12,
  10. Eric C Abadie13,14,
  11. Olivier Bruyère15,
  12. Cyrus Cooper16,17,18,
  13. Heidi Mäkinen19,
  14. Thierry Thomas20,21,
  15. Peter Tugwell22,
  16. Jean-Yves Reginster15
  17. on behalf of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO)
  1. 1Department of Internal Medicine III, Hietzing Hospital, Vienna, Austria
  2. 2Division of Rheumatology, Medical University Vienna, Vienna, Austria
  3. 3TRB Chemedica International SA, Geneva, Switzerland
  4. 4Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands
  5. 5Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands
  6. 6Leiden University Medical Centre, Leiden, The Netherlands
  7. 7Musculoskeletal Research Unit, NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton, Southampton, UK
  8. 8Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
  9. 9Department of Clinical Immunology and Rheumatology, Immunogenomics and Inflammation Research Unit EA 4130, University of Lyon 1, Edouard Herriot Hospital, Lyon, France
  10. 10Faculty of Health Sciences, University of Eastern Finland, Jyvaskyla Central Hospital, Jyvaskyla, Finland
  11. 11Department of Clinical Immunology and Rheumatology, Academic Medical Center, Amsterdam, The Netherlands
  12. 12Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands
  13. 13Euremed Consulting, Paris, France
  14. 14Universidade de Lisboa, Lisbon, Portugal
  15. 15Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium
  16. 16MRC Lifecourse Epidemiology Unit, NIHR Nutrition Biomedical Research Centre, University of Southampton, Southampton, UK
  17. 17NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
  18. 18Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, The Botnar Research Centre, University of Oxford, Oxford, UK
  19. 19Rheumatology Department, Tampere University Hospital, Tampere, Finland
  20. 20Rheumatology Department, University Hospital of Saint-Etienne, Saint-Etienne, France
  21. 21INSERM U1059, Université de Lyon, Lyon, France
  22. 22Department of Medicine, University of Ottawa, Ottawa, Canada
  1. Correspondence to Professor Josef S Smolen, Division of Rheumatology, Medical University Vienna, Waehringer Guertel 18-20, Vienna 1090, Austria; josef.smolen{at}


The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases convened a task force of experts in rheumatoid arthritis (RA) and clinical trial methodology to comment on the new draft ‘Guideline on clinical investigation of medicinal products for the treatment of RA’ released by the European Medicines Agency (EMA). Special emphasis was placed by the group on the development of new drugs for the treatment of early RA. In the absence of a clear definition of early RA, it was suggested that clinical investigations in this condition were conducted in disease-modifying antirheumatic drugs naïve patients with no more than 1 year disease duration. The expert group recommended using an appropriate improvement in disease activity (American College of Rheumatology (ACR) or Simplified/Clinical Disease Activity Index (SDAI/CDAI) response criteria) or low disease activity (by any score) as primary endpoints, with ACR/European League Against Rheumatism remission as a secondary endpoint. Finally, as compelling evidence showed that the Disease Acrivity Score using 28-joint counts (DAS28) might not provide a reliable definition of remission, or sometimes even low disease activity, the group suggested replacing DAS28 as a measurement instrument to evaluate disease activity in RA clinical trials. Proposed alternatives included SDAI, CDAI and Boolean criteria.

  • Early Rheumatoid Arthritis
  • Outcomes research
  • Treatment
  • DMARDs (biologic)
  • DMARDs (synthetic)

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