title: Clinically important changes in individual and composite measures of rheumatoid arthritis activity: thresholds applicable in clinical trials.
abstract: OBJECTIVE
  Thresholds of minimal clinically important improvement (MCII) are needed to plan and interpret clinical trials. We estimated MCIIs for the rheumatoid arthritis (RA) activity measures of patient global assessment, pain score, Health Assessment Questionnaire Disability Index (HAQ), Disease Activity Score-28 (DAS28), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI).
  
  
  METHODS
  In this prospective longitudinal study, we studied 250 patients who had active RA. Disease activity measures were collected before and either 1 month (for patients treated with prednisone) or 4 months (for patients treated with disease modifying medications or biologics) after treatment escalation. Patient judgments of improvement in arthritis status were related to prospectively assessed changes in the measures. MCIIs were changes that had a specificity of 0.80 for improvement based on receiver operating characteristic curve analysis. We used bootstrapping to provide estimates with predictive validity.
  
  
  RESULTS
  At baseline, the mean (±SD) DAS28-ESR (erythrocyte sedimentation rate) was 6.16±1.2 and mean SDAI was 38.6±14.8. Improvement in overall arthritis status was reported by 167 patients (66.8%). Patients were consistent in their ratings of improvement versus no change or worsening, with receiver operating characteristic curve areas ≥0.74. MCIIs with a specificity for improvement of 0.80 were: patient global assessment -18, pain score -20, HAQ -0.375, DAS28-ESR -1.2, DAS28-CRP (C-reactive protein) -1.0, SDAI -13, and CDAI -12.
  
  
  CONCLUSIONS
  MCIIs for individual core set measures were larger than previous estimates. Reporting the proportion of patients who meet these MCII thresholds can improve the interpretation of clinical trials in RA.
authors.affiliation: Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Ward
authors.affiliation: Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Lori C
authors.initials: LC
authors.lastname: Guthrie
authors.affiliation: Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Alba
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011446:Prospective Studies; D012720:Severity of Illness Index
chemical_list: D018501:Antirheumatic Agents
keywords: Disease Activity; Outcomes research; Rheumatoid Arthritis