title: How much does Disease Activity Score in 28 joints ESR and CRP calculations underestimate disease activity compared with the Simplified Disease Activity Index?
abstract: OBJECTIVE
  Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) is used instead of erythrocyte sedimentation rate (DAS28-ESR) to assess rheumatoid arthritis disease activity; however, values for remission and low disease activity (LDA) for DAS28-CRP have not been validated. American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) guidelines suggest remission should be calculated by Simplified Disease Activity Index (SDAI) rather than DAS28-ESR. We examined values of remission and LDA of DAS28-CRP that correspond to the respective cut-off points for DAS28-ESR and SDAI from five clinical trials.
  
  
  METHODS
  DAS28-CRP cut-offs that best correspond to DAS28-ESR remission <2.6 and LDA ≤3.2 were obtained by cumulative distribution plots, receiver operating curves and maximum concordance and averaged for each approach, treatment group and study. Level of agreement between DAS28-CRP and DAS28-ESR remission and LDA cut-offs was compared against each other and versus SDAI remission ≤3.3 and LDA ≤11.
  
  
  RESULTS
  Percentage of patients who achieved remission and LDA by DAS28-ESR cut-offs was greater for DAS28-CRP versus DAS28-ESR regardless of patient population or treatment group. Discordance between CRP and ESR cut-offs ranged from 4%-26% and 8%-23% for remission and LDA, respectively, and 19%-40% and 6%-11% for DAS28-CRP versus SDAI, respectively. Estimated (range) remission and LDA thresholds were 2.4 (2.2-2.6) and 2.9 (2.6-3.3), 1.9 (1.6-2.2) and 3.1 (3.1-3.3) and 2.2 (1.1-2.9) and 3.6 (3.4-4.0) for DAS28-CRP versus DAS28-ESR, DAS28-CRP versus SDAI and DAS28-ESR versus SDAI, respectively.
  
  
  CONCLUSIONS
  DAS28-CRP underestimates disease activity when using cut-off points validated for DAS28-ESR; therefore, DAS28-ESR cut-off values should not be applied to DAS28-CRP. Although DAS28-CRP and DAS28-ESR cut-offs for LDA ≤3.2 correspond to SDAI LDA, neither corresponds well to SDAI remission.
authors.affiliation: Metroplex Clinical Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Fleischmann
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Désirée
authors.initials: D
authors.lastname: van der Heijde
authors.affiliation: Department of Specialty Care, Pfizer Inc, Collegeville, Pennsylvania, USA.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Koenig
authors.affiliation: Department of Specialty Care, Pfizer Inc, Collegeville, Pennsylvania, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Pedersen
authors.affiliation: Department of Specialty Care, Pfizer Inc, Collegeville, Pennsylvania, USA.
authors.forename: Annette
authors.initials: A
authors.lastname: Szumski
authors.affiliation: Department of Specialty Care, Pfizer Inc, Collegeville, Pennsylvania, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Marshall
authors.affiliation: Department of Specialty Care, Pfizer Inc, Collegeville, Pennsylvania, USA.
authors.forename: Eustratios
authors.initials: E
authors.lastname: Bananis
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis; D002986:Clinical Trials as Topic; D006801:Humans; D017063:Outcome Assessment, Health Care / Q000592:standards; D012372:ROC Curve; D012074:Remission Induction; D012720:Severity of Illness Index
chemical_list: D018501:Antirheumatic Agents; D002097:C-Reactive Protein
keywords: Anti-TNF; DAS28; Disease Activity; Rheumatoid Arthritis; TNF-alpha