title: Clinical trials of new drugs for the treatment of rheumatoid arthritis: focus on early disease.
abstract: 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.
authors.affiliation: Department of Internal Medicine III, Hietzing Hospital, Vienna, Austria Division of Rheumatology, Medical University Vienna, Vienna, Austria.
authors.forename: Josef S
authors.identifier: 0000-0002-8899-9087
authors.initials: JS
authors.lastname: Smolen
authors.affiliation: TRB Chemedica International SA, Geneva, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Collaud Basset
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Boers
authors.affiliation: Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Breedveld
authors.affiliation: Musculoskeletal Research Unit, NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton, Southampton, UK.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Edwards
authors.affiliation: Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: Tore K
authors.initials: TK
authors.lastname: Kvien
authors.affiliation: Department of Clinical Immunology and Rheumatology, Immunogenomics and Inflammation Research Unit EA 4130, University of Lyon 1, Edouard Herriot Hospital, Lyon, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Miossec
authors.affiliation: Faculty of Health Sciences, University of Eastern Finland, Jyvaskyla Central Hospital, Jyvaskyla, Finland.
authors.forename: Tuulikki
authors.initials: T
authors.lastname: Sokka-Isler
authors.affiliation: Amsterdam Rheumatology and Immunology Center, Amsterdam, The Netherlands Department of Clinical Immunology and Rheumatology, Academic Medical Center, Amsterdam, The Netherlands Department of Rheumatology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Ronald F
authors.initials: RF
authors.lastname: van Vollenhoven
authors.affiliation: Euremed Consulting, Paris, France Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Abadie
authors.affiliation: Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.
authors.forename: Olivier
authors.initials: O
authors.lastname: Bruyère
authors.affiliation: MRC Lifecourse Epidemiology Unit, NIHR Nutrition Biomedical Research Centre, University of Southampton, Southampton, UK NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK Oxford NIHR Musculoskeletal Biomedical Research Unit, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, The Botnar Research Centre, University of Oxford, Oxford, UK.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Cooper
authors.affiliation: Rheumatology Department, Tampere University Hospital, Tampere, Finland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Mäkinen
authors.affiliation: Rheumatology Department, University Hospital of Saint-Etienne, Saint-Etienne, France INSERM U1059, Université de Lyon, Lyon, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Thomas
authors.affiliation: Department of Medicine, University of Ottawa, Ottawa, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Tugwell
authors.affiliation: Department of Public Health, Epidemiology and Health Economics, University of Liège, Liège, Belgium.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Reginster
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D002986:Clinical Trials as Topic / Q000379:methods*; D015507:Drugs, Investigational / Q000627:therapeutic use*; D042241:Early Diagnosis; D005060:Europe; D006801:Humans; D017410:Practice Guidelines as Topic; D012720:Severity of Illness Index
chemical_list: D018501:Antirheumatic Agents; D015507:Drugs, Investigational
keywords: DMARDs (biologic); DMARDs (synthetic); Early Rheumatoid Arthritis; Outcomes research; Treatment