title: Two-year clinical and radiographic results with combination etanercept-methotrexate therapy versus monotherapy in early rheumatoid arthritis: a two-year, double-blind, randomized study.
abstract: OBJECTIVE
  To evaluate how continuation of and alterations to initial year 1 combination etanercept-methotrexate (MTX) therapy and MTX monotherapy regimens affect long-term remission and radiographic progression in early, active rheumatoid arthritis.
  
  
  METHODS
  Subjects were randomized at baseline for the entire 2-year period; those who completed 1 year of treatment with combination or MTX monotherapy entered year 2. The original combination group either continued combination therapy (the EM/EM group; n = 111) or received etanercept monotherapy (the EM/E group; n = 111) in year 2; the original MTX monotherapy group either received combination therapy (the M/EM group; n = 90) or continued monotherapy (the M/M group; n = 99) in year 2. Efficacy end points included remission (a Disease Activity Score in 28 joints [DAS28] <2.6) and radiographic nonprogression (change in the modified Sharp/van der Heijde score < or = 0.5) at year 2. A last observation carried forward analysis from the modified intention-to-treat population (n = 398) and a post hoc nonresponder imputation (NRI) analysis (n = 528) were performed for remission.
  
  
  RESULTS
  At year 2, DAS28 remission was achieved by 62/108, 54/108, 51/88, and 33/94 subjects in the EM/EM, EM/E, M/EM, and M/M groups, respectively (P < 0.01 for the EM/EM and M/EM groups versus the M/M group). This effect was corroborated by a more conservative post hoc 2-year NRI analysis, with remission observed in 59/131, 50/134, 48/133, and 29/130 of the same respective groups (P < 0.05 for each of the EM/EM, EM/E, and M/EM groups versus the M/M group). The proportions of subjects achieving radiographic nonprogression (n = 360) were 89/99, 74/99, 59/79, and 56/83 in the EM/EM (P < 0.01 versus each of the other groups), EM/E, M/EM, and M/M groups, respectively. No new safety signals or between-group differences in serious adverse events were seen.
  
  
  CONCLUSIONS
  Early sustained combination etanercept-MTX therapy was consistently superior to MTX monotherapy. Combination therapy resulted in important clinical and radiographic benefits over 2 study years, without significant additional safety risk.
authors.affiliation: University of Leeds, NIHR Leeds Musculoskeletal Biomedical Research Unit, [corrected] Leeds, UK. p.emery@leeds.ac.uk
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Breedveld
authors.forename: Désirée
authors.initials: D
authors.lastname: van der Heijde
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Ferraccioli
authors.forename: Maxime
authors.initials: M
authors.lastname: Dougados
authors.forename: Deborah
authors.initials: D
authors.lastname: Robertson
authors.forename: Ronald
authors.initials: R
authors.lastname: Pedersen
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Koenig
authors.forename: Bruce
authors.initials: B
authors.lastname: Freundlich
mesh_terms: D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D018450:Disease Progression; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000627:therapeutic use*; D008875:Middle Aged; D011859:Radiography; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept; D008727:Methotrexate