title: Tocilizumab combination therapy or monotherapy or methotrexate monotherapy in methotrexate-naive patients with early rheumatoid arthritis: 2-year clinical and radiographic results from the randomised, placebo-controlled FUNCTION trial.
abstract: OBJECTIVE
  Investigate whether the efficacy and safety of intravenous tocilizumab (TCZ) demonstrated at week 52 in patients with early rheumatoid arthritis (RA) are maintained to week 104.
  
  
  METHODS
  Methotrexate (MTX)-naive patients with early progressive RA were randomly assigned to double-blind 4 mg/kg TCZ+MTX, 8 mg/kg TCZ+MTX, 8 mg/kg TCZ+placebo or placebo+MTX for 104 weeks. Patients not receiving 8 mg/kg TCZ and not achieving Disease Activity Score-28 joints (DAS28-erythrocyte sedimentation rate (ESR)) ≤3.2 at week 52 switched to escape therapy (8 mg/kg TCZ+MTX). Analyses were exploratory.
  
  
  RESULTS
  Intent-to-treat and safety populations included 1157 and 1153 patients, respectively. DAS28-ESR remission (<2.6) rates were maintained from weeks 52 to 104 (eg, 8 mg/kg TCZ+MTX, 49.3% to 47.6%). Placebo+MTX and 4 mg/kg TCZ+MTX escape patients' week 104 response rates were 51.4% and 30.5%, respectively. Inhibition of radiographic progression was maintained with 8 mg/kg TCZ (eg, 8 mg/kg TCZ+MTX mean (SD) change from baseline in modified total Sharp score: 0.13 (1.28), week 52; 0.19 (2.08), week 104). The safety profile of TCZ was consistent with that of previous reports.
  
  
  CONCLUSIONS
  Patients with early RA treated with TCZ monotherapy or TCZ+MTX maintained clinical benefits during their second year of treatment with no new safety signals.
  
  
  BACKGROUND
  NCT01007435; Results.
authors.affiliation: Charité-Universitätsmedizin Berlin, Free University and Humboldt University of Berlin, Berlin, Germany.
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Burmester
authors.affiliation: Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
authors.forename: William F
authors.initials: WF
authors.lastname: Rigby
authors.affiliation: Karolinska Institute, Stockholm, Sweden.
authors.forename: Ronald F
authors.initials: RF
authors.lastname: van Vollenhoven
authors.affiliation: UMass Memorial Medical Center and University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Jonathan
authors.identifier: http://orcid.org/0000-0002-8970-4260
authors.initials: J
authors.lastname: Kay
authors.affiliation: University of Cologne, Cologne, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rubbert-Roth
authors.affiliation: Hospital Universitario Marqués de Valdecilla, Santander, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Blanco
authors.affiliation: Genentech, South San Francisco, California, USA.
authors.forename: Alysha
authors.initials: A
authors.lastname: Kadva
authors.affiliation: Roche Products Ltd., Welwyn Garden City, UK.
authors.forename: Sophie
authors.initials: S
authors.lastname: Dimonaco
mesh_terms: D000328:Adult; 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; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007596:Joints / Q000000981:diagnostic imaging; D008297:Male; D054539:Medication Therapy Management; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011859:Radiography; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab; D008727:Methotrexate
keywords: DMARDs (biologic); Early Rheumatoid Arthritis; Methotrexate