title: Evaluation of the Disease Activity Score in Twenty-Eight Joints-Based Flare Definitions in Rheumatoid Arthritis: Data From a Three-Year Clinical Trial.
abstract: OBJECTIVE
  To assess the flare rate using published criteria (Disease Activity Score in 28 joints [DAS28-2] increase between visits of >1.2 or >0.6 if current DAS28 ≥3.2) in patients receiving constant treatment, and to compare published flare criteria to criteria used by study investigators after biologic treatment discontinuation in the ACT-RAY study.
  
  
  METHODS
  Patients with rheumatoid arthritis (n = 553) were randomized to add tocilizumab to ongoing methotrexate, or switch to tocilizumab plus placebo. If DAS28 ≤3.2 occurred at week 24, treatment remained constant until week 52; here we assessed the DAS28-2 flare rate. Between weeks 52 and 104, patients in sustained remission (DAS28 <2.6 at 2 consecutive visits 12 weeks apart) discontinued tocilizumab and were assessed every 4 weeks. Per protocol, flare was defined as a worsening of disease activity that required treatment beyond the permitted therapy based on investigator opinions (investigator flare) and was compared with the DAS28-2 definition.
  
  
  RESULTS
  After tocilizumab discontinuation, DAS28-2 was sensitive (88-100%), but not specific (57-65%), for detecting investigator flare. Under constant treatment, DAS28-2 criteria were met in 136 cases per 100 patient-years despite stable disease activity. Sustained flares were infrequent. Other DAS28-based criteria led to similar conclusions.
  
  
  CONCLUSIONS
  DAS28-based flare occurred more often than investigator-defined flares after biologic agent discontinuation. More stringent criteria may be more appropriate for clinical practice.
authors.affiliation: Hôpital Cochin, Paris, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Dougados
authors.affiliation: Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.affiliation: Cardiff University School of Medicine, Cardiff, UK.
authors.forename: Ernest H
authors.initials: EH
authors.lastname: Choy
authors.affiliation: Johns Hopkins University, Baltimore, Maryland.
authors.forename: Clifton O
authors.initials: CO
authors.lastname: Bingham
authors.affiliation: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Maher
authors.initials: M
authors.lastname: Aassi
authors.affiliation: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Corrado
authors.initials: C
authors.lastname: Bernasconi
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D018501:Antirheumatic Agents / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000188:drug therapy; D001208:Asia; D001688:Biological Products / Q000008:administration & dosage; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D005060:Europe; D006801:Humans; D007596:Joints / Q000187:drug effects / Q000473:pathology*; D008727:Methotrexate / Q000008:administration & dosage; D011237:Predictive Value of Tests; D012074:Remission Induction; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001688:Biological Products; C502936:tocilizumab; D008727:Methotrexate