title: The Canadian methotrexate and etanercept outcome study: a randomised trial of discontinuing versus continuing methotrexate after 6 months of etanercept and methotrexate therapy in rheumatoid arthritis.
abstract: OBJECTIVE
  To determine if withdrawing methotrexate (MTX) after 6 months of combination etanercept (ETN)+MTX, in MTX-inadequate responders with active rheumatoid arthritis (RA), is non-inferior to continuing ETN+MTX.
  
  
  METHODS
  Tumour necrosis factor-inhibitor naïve RA patients with disease activity score 28 (DAS28)≥3.2, swollen joint count≥3, despite stable MTX, were treated with ETN+MTX for 6 months, followed by randomisation to either continue ETN+MTX or switch to ETN monotherapy for an additional 18 months. The primary endpoint was change in DAS28 from 6-month randomisation to 12 months. The non-inferiority margin of change in DAS28 was 0.6, with prespecified analyses (DAS28<3.2 vs DAS28≥3.2).
  
  
  RESULTS
  205 patients were randomised. DAS28 was stable in patients on ETN+MTX and increased slightly in patients on ETN monotherapy from 6 to 12 months. Non-inferiority was not achieved, with an adjusted difference of 0.4 (0.1 to 0.7) between the ETN and the ETN+MTX groups, for the month 6-12 change in DAS28. However, patients who achieved low disease activity (LDA; DAS28<3.2) at 6 months had a similar disease activity at 12 months, whether on monotherapy or combination therapy (DAS28 change 0.7 ETN vs 0.57 ETN+MTX, p=0.8148). Conversely, for patients who did not reach LDA at 6 months, those on ETN monotherapy had increased disease activity at 12 months, while disease activity continued to decrease for patients on combination therapy, at 12 months (DAS28 change 0.4 ETN vs -0.4 ETN+MTX, p=0.0023).
  
  
  CONCLUSIONS
  Non-inferiority was not achieved. Withdrawing MTX after 6 months of continuation ETN+MTX in MTX inadequate responders did not yield the same degree of improvement between 6 and 12 months compared with continuing ETN+MTX.
  
  
  BACKGROUND
  ClinicalTrials.gov-NCT00654368.
authors: Division of Rheumatology, Department of Medicine, The University of Western Ontario, St Joseph's Health Centre, London, Ontario, Canada.
authors: Janet E
authors: JE
authors: Pope
authors: Department of Rheumatology, Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.
authors: Boulos
authors: B
authors: Haraoui
authors: Southlake Regional Health Centre, Newmarket, Ontario, Canada.
authors: J Carter
authors: JC
authors: Thorne
authors: Amgen Canada Inc., Mississauga, Ontario, Canada.
authors: Andrew
authors: A
authors: Vieira
authors: Amgen Canada Inc., Mississauga, Ontario, Canada.
authors: Melanie
authors: M
authors: Poulin-Costello
authors: Department of Rheumatology, Mount Sinai Hospital, Rebecca MacDonald Centre For Arthritis & Autoimmune Diseases, Toronto, Ontario, Canada.
authors: Edward C
authors: EC
authors: Keystone
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D002170:Canada; D004359:Drug Therapy, Combination; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000068800:Etanercept; D008727:Methotrexate
keywords: Anti-TNF; DMARDs (biologic); Methotrexate; Rheumatoid Arthritis
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