title: Definition of treatment response in rheumatoid arthritis based on the simplified and the clinical disease activity index.
abstract: BACKGROUND
  The simplified disease activity index (SDAI) and the clinical disease activity index (CDAI) are established instruments to measure disease activity in rheumatoid arthritis (RA). To date, no validated response definitions for the SDAI and CDAI are available.
  
  
  OBJECTIVE
  The authors aimed to define minor, moderate and major response criteria for the SDAI.
  
  
  METHODS
  The authors used data from two clinical trials on infliximab versus methotrexate in early (ASPIRE) or established (ATTRACT) RA, and identified the three SDAI cutpoints based on the best agreement (by κ statistics) with the American College of Rheumatology (ACR)20/50/70 responses. Cutpoints were then tested for different aspects of validity in the trial datasets and in a Norwegian disease modifying antirheumatic drug prescription dataset (NOR-DMARD).
  
  
  RESULTS
  Based on agreement with the ACR response, the minor, moderate and major responses were identified as SDAI 50%, 70% and 85% improvement. These cutpoints had good face validity concerning the disease activity states achieved by the different response definitions. Construct validity was shown by a clear association of increasing SDAI response categories with increasing levels of functional improvement, achievement of better functional states and lower annual radiographic progression. Across SDAI 50/70/85, the sensitivities regarding a patient-perceived improvement decreased (73%/39%/22%) and the specificities increased (61%/89%/96%) in a meaningful way. Further, the cutpoints discriminated the different treatment arms in ASPIRE and ATTRACT. The same cutpoints were used for the CDAI, with similar results in the validation analyses.
  
  
  CONCLUSIONS
  These new response criteria expand the usefulness of the SDAI and CDAI for their use as endpoints in clinical trials beyond the definition of disease activity categories.
authors.affiliation: Medical University of Vienna, Department of Rheumatology, Spitalgasse 23, 1090 Vienna, Austria. daniel.aletaha@meduniwien.ac.at
authors.forename: Daniel
authors.initials: D
authors.lastname: Aletaha
authors.forename: Jose
authors.initials: J
authors.lastname: Martinez-Avila
authors.forename: Tore K
authors.initials: TK
authors.lastname: Kvien
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D002986:Clinical Trials as Topic; D005260:Female; D006304:Health Status; D006801:Humans; D000069285:Infliximab; D007596:Joints / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015415:Biomarkers; D000069285:Infliximab; D008727:Methotrexate