title: Rapid improvement in the signs and symptoms of rheumatoid arthritis following certolizumab pegol treatment predicts better longterm outcomes: post-hoc analysis of a randomized controlled trial.
abstract: OBJECTIVE
  To assess the kinetics of response to certolizumab pegol (CZP), and association between rapid response and longterm outcomes, in patients with active rheumatoid arthritis (RA).
  
  
  METHODS
  This was a post-hoc analysis of the randomized, double-blind RAPID 1 study in patients who received methotrexate (MTX) and either CZP 200 mg subcutaneously or placebo every 2 weeks for 52 weeks. Clinical and radiographic outcomes at Week 52 were evaluated based on the Disease Activity Score 28 (DAS28) ≥ 1.2 and American College of Rheumatology 20% (ACR20) responses at Week 6 and Week 12.
  
  
  RESULTS
  Clinical responses [European League Against Rheumatism (EULAR), DAS28 ≥ 1.2, and ACR20 responses] were rapid in CZP-treated patients. Week 12 DAS28 ≥ 1.2 responders had better clinical and radiographic outcomes at Week 52 compared with nonresponders. Among Week 12 responders, incremental benefit of earlier response was observed: Week 6 DAS28 ≥ 1.2 responders and ACR20 responders had significantly higher ACR response rates and were more likely to achieve remission at Week 52 than Week 12 responders. Patients with a clinical response at Week 6 had faster, more meaningful sustained improvements in patient-derived outcomes than those responding by Week 12 only.
  
  
  CONCLUSIONS
  Rapid attainment of clinical response in patients with RA is associated with improved longterm outcomes. Analysis of the kinetics of response to CZP during the first 12 weeks of therapy potentially permits informed prediction of clinical success or need to alter treatment. In patients not achieving a clinical response at Week 12 treatment adjustment should be considered. Trial registration NCT00152386.
authors.affiliation: Mount Sinai Hospital, Joseph and Wolf Lebovic Building, Second Floor, Room 2-006, 60 Murray Street, Toronto, Ontario M5G 1X5. edkeystone@mtsinai.on.ca
authors.forename: Edward C
authors.initials: EC
authors.lastname: Keystone
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Curtis
authors.forename: Roy M
authors.initials: RM
authors.lastname: Fleischmann
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Furst
authors.forename: Dinesh
authors.initials: D
authors.lastname: Khanna
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Mease
authors.forename: Michael H
authors.initials: MH
authors.lastname: Schiff
authors.forename: Geoffroy
authors.initials: G
authors.lastname: Coteur
authors.forename: Owen
authors.initials: O
authors.lastname: Davies
authors.forename: Bernard
authors.initials: B
authors.lastname: Combe
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000188:drug therapy*; D000068582:Certolizumab Pegol; D004311:Double-Blind Method; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D008137:Longitudinal Studies; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011379:Prognosis; D011859:Radiography; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007140:Immunoglobulin Fab Fragments; D011092:Polyethylene Glycols; D000068582:Certolizumab Pegol; D008727:Methotrexate