title: Timing and magnitude of initial change in disease activity score 28 predicts the likelihood of achieving low disease activity at 1 year in rheumatoid arthritis patients treated with certolizumab pegol: a post-hoc analysis of the RAPID 1 trial.
abstract: OBJECTIVE
  To determine the relationship between timing and magnitude of Disease Activity Score [DAS28(ESR)] nonresponse (DAS28 improvement thresholds not reached) during the first 12 weeks of treatment with certolizumab pegol (CZP) plus methotrexate, and the likelihood of achieving low disease activity (LDA) at 1 year in patients with rheumatoid arthritis.
  
  
  METHODS
  In a post-hoc analysis of the RAPID 1 study, patients achieving LDA [DAS28(ESR) ≤ 3.2] at Year 1 were assessed according to DAS28 nonresponse at various timepoints within the first 12 weeks.
  
  
  RESULTS
  Seven-hundred eighty-three patients were included (CZP 200 mg, n = 393; CZP 400 mg, n = 390). A total of 86.9% of patients in the CZP 200 mg group had a DAS28 improvement of ≥ 1.2 by Week 12. Of the 13.1% of patients with DAS28 improvement < 1.2 by Week 12, only 2.0% had LDA at Year 1. Failure to achieve LDA at Year 1 depended on timing of nonresponse - 22.3%, 8.4%, and 2.0% of patients with DAS28 improvement < 1.2 by Weeks 1, 6, and 12, respectively, had LDA at Year 1 - and magnitude of initial lack of DAS28 improvement; for example, compared with the patients with DAS28 < 1.2 improvement, fewer patients with DAS28 < 0.6 had LDA at Year 1 (17.4%, 2.4%, and 0.0% at Weeks 1, 6, and 12, respectively).
  
  
  CONCLUSIONS
  Failure to achieve improvement in DAS28 within the first 12 weeks of therapy was predictive of a low probability of achieving LDA at Year 1. Moreover, the accuracy of the prediction was found to be strongly dependent on the magnitude and timing of the lack of the response. (Clinical Trial Registration Nos. NCT00152386 and NCT00175877).
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. d.vanderheijde@kpnplanet.nl
authors.forename: Désirée
authors.initials: D
authors.lastname: van der Heijde
authors.forename: Edward C
authors.initials: EC
authors.lastname: Keystone
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Curtis
authors.forename: Robert B
authors.initials: RB
authors.lastname: Landewé
authors.forename: Michael H
authors.initials: MH
authors.lastname: Schiff
authors.forename: Dinesh
authors.initials: D
authors.lastname: Khanna
authors.forename: Tore K
authors.initials: TK
authors.lastname: Kvien
authors.forename: Lucian
authors.initials: L
authors.lastname: Ionescu
authors.forename: Leon M
authors.initials: LM
authors.lastname: Gervitz
authors.forename: Owen R
authors.initials: OR
authors.lastname: Davies
authors.forename: Kristel
authors.initials: K
authors.lastname: Luijtens
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Furst
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D000068582:Certolizumab Pegol; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007140:Immunoglobulin Fab Fragments; D011092:Polyethylene Glycols; D000068582:Certolizumab Pegol; D008727:Methotrexate