title: A randomised controlled trial of etanercept and methotrexate to induce remission in early inflammatory arthritis: the EMPIRE trial.
abstract: OBJECTIVE
  To compare the efficacy of etanercept (ETN) and methotrexate (MTX) versus MTX monotherapy for remission induction in patients with early inflammatory arthritis.
  
  
  METHODS
  In a 78-week multicentre randomised placebo-controlled superiority trial, 110 DMARD-naïve patients with early clinical synovitis (≥1 tender and swollen joint, and within 3 months of diagnosis) and either rheumatoid factor, anticitrullinated protein antibodies or shared epitope positive were randomised 1:1 to receive MTX+ETN or MTX+placebo (PBO) for 52 weeks. Injections (ETN or PBO) were stopped in all patients at week 52. In those with no tender or swollen joints (NTSJ) for >26 weeks, injections were stopped early. If patients had NTSJ >12 weeks after stopping the injections, MTX was weaned. The primary endpoint was NTSJ at week 52.
  
  
  RESULTS
  No statistically significant difference was seen for the primary endpoint (NTSJ at week 52 (32.5% vs 28.1% [adjusted OR 1.32 (0.56 to 3.09), p=0.522]) in the MTX+ETN and MTX+PBO groups, respectively). The secondary endpoints did not differ between groups at week 52 or 78. Exploratory analyses showed a higher proportions of patients with DAS28-CRP<2.6 in the MTX+ETN group at week 2 (38.5% vs 9.2%, adjusted OR 8.87 (2.53 to 31.17), p=0.001) and week 12 (65.1% vs 43.8%, adjusted OR 2.49 (1.12 to 5.54), p=0.026).
  
  
  CONCLUSIONS
  In this group of patients with early inflammatory arthritis, almost a third had no tender, swollen joints after 1 year. MTX+ETN was not superior to MTX monotherapy in achieving this outcome. Clinical responses, however, including DAS28-CRP<2.6, were achieved earlier with MTX+ETN combination therapy.
  
  
  BACKGROUND
  The EMPIRE trial is registered on the following trial registries: Eudract-2005-005467-29; ISRCTN 55428162 (http://www.controlled-trials.com/ISRCTN55428162/EMPIRE). The full trial protocol can be obtained from the corresponding author.
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, , Leeds, UK.
authors.forename: J L
authors.initials: JL
authors.lastname: Nam
authors.forename: E
authors.initials: E
authors.lastname: Villeneuve
authors.forename: E M A
authors.initials: EM
authors.lastname: Hensor
authors.forename: R J
authors.initials: RJ
authors.lastname: Wakefield
authors.forename: P G
authors.initials: PG
authors.lastname: Conaghan
authors.forename: M J
authors.initials: MJ
authors.lastname: Green
authors.forename: A
authors.initials: A
authors.lastname: Gough
authors.forename: M
authors.initials: M
authors.lastname: Quinn
authors.forename: R
authors.initials: R
authors.lastname: Reece
authors.forename: S R
authors.initials: SR
authors.lastname: Cox
authors.forename: M H
authors.initials: MH
authors.lastname: Buch
authors.forename: D M
authors.initials: DM
authors.lastname: van der Heijde
authors.forename: P
authors.initials: P
authors.lastname: Emery
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001168:Arthritis / Q000188:drug therapy* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D061345:Early Medical Intervention / Q000379:methods; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D060828:Induction Chemotherapy / Q000379:methods; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D012074:Remission Induction / Q000379:methods; D012217:Rheumatoid Factor / Q000276:immunology; D013585:Synovitis / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D001323:Autoantibodies; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D012217:Rheumatoid Factor; D000068800:Etanercept; D008727:Methotrexate
keywords: Anti-TNF; DMARDs (biologic); Early Rheumatoid Arthritis; Methotrexate