title: Clinical, functional, and radiographic implications of time to treatment response in patients with early rheumatoid arthritis: a posthoc analysis of the PREMIER study.
abstract: OBJECTIVE
  Rheumatoid arthritis (RA) treatment recommendations suggest target attainment within the first 3 months of therapy, yet delayed clinical responses can occur. This analysis assessed the longterm clinical, functional, and radiographic outcomes associated with delayed responses to methotrexate (MTX) monotherapy or to the combination of adalimumab (ADA) + MTX.
  
  
  METHODS
  In this posthoc analysis, patients with early RA who received MTX monotherapy or ADA + MTX in the PREMIER study were categorized based on clinical responses at 3 and 6 months [American College of Rheumatology response, 28-joint Disease Activity Score (DAS28)-C-reactive protein (CRP) improvement and targets]. "Month 3" responders met the clinical measure at both months 3 and 6, and "Month 6" responders met the clinical measure only at Month 6. The odds of achieving longterm outcomes [remission (DAS28-CRP < 2.6), normal function (Health Assessment Questionnaire-Disability Index < 0.5), or rapid radiographic progression (Δ modified total Sharp score > 3 U/yr)] were modeled using logistic regression, including treatment, response, and interaction.
  
  
  RESULTS
  A delayed or low-level response was associated with poorer longterm outcomes. Generally, MTX Month 6 responders demonstrated worse clinical, functional, and radiographic outcomes than Month 3 MTX and Month 3 or 6 ADA + MTX responders. Although similar longterm benefit was observed for ADA + MTX responders, delayed (Month 6) responders exhibited downward trends in clinical, functional, and radiographic outcomes that were comparable with those experienced by Month 3 MTX responders.
  
  
  CONCLUSIONS
  Response speed and magnitude predict longterm outcomes in patients with early RA treated with MTX or ADA + MTX. MTX-treated patients failing to demonstrate a Month 3 clinical response have less-favorable outcomes than other groups, while outcomes in ADA + MTX Month 3 and Month 6 responders tended to be comparable.
authors.affiliation: From the University of Toronto, Toronto, Ontario; the University of Montreal, Montreal, Quebec, Canada; AbbVie Inc., North Chicago, Illinois; and the University of California San Diego, La Jolla, California, USA.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Keystone
authors.forename: Boulos
authors.initials: B
authors.lastname: Haraoui
authors.forename: Benoît
authors.initials: B
authors.lastname: Guérette
authors.forename: Neelufar
authors.initials: N
authors.lastname: Mozaffarian
authors.forename: Shufang
authors.initials: S
authors.lastname: Liu
authors.forename: Arthur
authors.initials: A
authors.lastname: Kavanaugh
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005528:Foot / Q000000981:diagnostic imaging; D006225:Hand / Q000000981:diagnostic imaging; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011859:Radiography; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014953:Wrist / Q000000981:diagnostic imaging
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D000068879:Adalimumab; D008727:Methotrexate
keywords: DISEASE ACTIVITY; METHOTREXATE; RHEUMATOID ARTHRITIS; TUMOR NECROSIS FACTOR INHIBITORS