title: The comparative effectiveness of oral versus subcutaneous methotrexate for the treatment of early rheumatoid arthritis.
abstract: OBJECTIVE
  To determine the comparative effectiveness of oral versus subcutaneous methotrexate (MTX) as initial therapy for patients with early rheumatoid arthritis (ERA).
  
  
  METHODS
  Patients with ERA (symptoms ≤1 year) initiating MTX therapy were included from a multicentre, prospective cohort study. We compared the effectiveness between starting with oral versus subcutaneous MTX over the first year. Longitudinal multivariable models, adjusted for potential baseline and time-varying confounders, were used to compare treatment changes due to inefficacy or toxicity and treatment efficacy (Disease Activity Score-28 (DAS-28), DAS-28 remission and Health Assessment Questionnaire-Disability Index (HAQ-DI)).
  
  
  RESULTS
  666 patients were included (417 oral MTX, 249 subcutaneous MTX). Patients prescribed subcutaneous MTX were prescribed a higher dose of MTX (mean dose over first three months 22.3 mg vs 17.2 mg/week). At 1 year, 49% of patients initially treated with subcutaneous MTX had changed treatment compared with 77% treated with oral MTX. After adjusting for potential confounders, subcutaneous MTX was associated with a lower rate of treatment failure ((HR (95% CI) 0.55 (0.39 to 0.79)). Most treatment failures were due to inefficacy with no difference in failure due to toxicity. In multivariable models, subcutaneous MTX was also associated with lower average DAS-28 scores (mean difference (-0.38 (95% CI -0.64 to -0.10)) and a small difference in DAS-28 remission (OR 1.2 (95% CI 1.1 to 1.3)). There was no significant difference in sustained remission or HAQ-DI (p values 0.43 and 0.75).
  
  
  CONCLUSIONS
  Initial treatment with subcutaneous MTX was associated with lower rates of treatment changes, no difference in toxicity and some improvements in disease control versus oral MTX over the first year in patients with ERA.
authors.affiliation: Institute of Health, Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada Department of Medicine, University of Calgary, Calgary, Alberta, Canada McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Glen S
authors.initials: GS
authors.lastname: Hazlewood
authors.affiliation: Southlake Regional Health Centre, Newmarket, Ontario, Canada.
authors.forename: J Carter
authors.initials: JC
authors.lastname: Thorne
authors.affiliation: Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Pope
authors.affiliation: Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Daming
authors.initials: D
authors.lastname: Lin
authors.affiliation: Southlake Regional Health Centre, Newmarket, Ontario, Canada.
authors.forename: Diane
authors.initials: D
authors.lastname: Tin
authors.affiliation: Centre Hospitalier Universitaire de Sherbrooke (CHUS), Sherbrooke University, Sherbrooke, Quebec, Canada.
authors.forename: Gilles
authors.initials: G
authors.lastname: Boire
authors.affiliation: University of Montreal Hospital Research Centre (CRCHUM), Montreal, Quebec, Canada.
authors.forename: Boulos
authors.initials: B
authors.lastname: Haraoui
authors.affiliation: University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Hitchon
authors.affiliation: Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Keystone
authors.affiliation: University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Shahin
authors.initials: S
authors.lastname: Jamal
authors.affiliation: Mount Sinai Hospital, Toronto, Ontario, Canada Hospital for Special Surgery, New York, New York, USA.
authors.forename: Vivian P
authors.initials: VP
authors.lastname: Bykerk
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology; D057186:Comparative Effectiveness Research; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D015999:Multivariate Analysis; D011446:Prospective Studies; D012074:Remission Induction; D012720:Severity of Illness Index; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate
keywords: Early Rheumatoid Arthritis; Methotrexate; Outcomes research