title: Tocilizumab in early progressive rheumatoid arthritis: FUNCTION, a randomised controlled trial.
abstract: OBJECTIVE
  The efficacy of tocilizumab (TCZ), an anti-interleukin-6 receptor antibody, has not previously been evaluated in a population consisting exclusively of patients with early rheumatoid arthritis (RA).
  
  
  METHODS
  In a double-blind randomised controlled trial (FUNCTION), 1162 methotrexate (MTX)-naive patients with early progressive RA were randomly assigned (1:1:1:1) to one of four treatment groups: 4 mg/kg TCZ+MTX, 8 mg/kg TCZ+MTX, 8 mg/kg TCZ+placebo and placebo+MTX (comparator group). The primary outcome was remission according to Disease Activity Score using 28 joints (DAS28-erythrocyte sedimentation rate (ESR) <2.6) at week 24. Radiographic and physical function outcomes were also evaluated. We report results through week 52.
  
  
  RESULTS
  The intent-to-treat population included 1157 patients. Significantly more patients receiving 8 mg/kg TCZ+MTX and 8 mg/kg TCZ+placebo than receiving placebo+MTX achieved DAS28-ESR remission at week 24 (45% and 39% vs 15%; p<0.0001). The 8 mg/kg TCZ+MTX group also achieved significantly greater improvement in radiographic disease progression and physical function at week 52 than did patients treated with placebo+MTX (mean change from baseline in van der Heijde-modified total Sharp score, 0.08 vs 1.14 (p=0.0001); mean reduction in Health Assessment Disability Index, -0.81 vs -0.64 (p=0.0024)). In addition, the 8 mg/kg TCZ+placebo and 4 mg/kg TCZ+MTX groups demonstrated clinical efficacy that was at least as effective as MTX for these key secondary endpoints. Serious adverse events were similar among treatment groups. Adverse events resulting in premature withdrawal occurred in 20% of patients in the 8 mg/kg TCZ+MTX group.
  
  
  CONCLUSIONS
  TCZ is effective in combination with MTX and as monotherapy for the treatment of patients with early RA.
  
  
  BACKGROUND
  ClinicalTrials.gov, number NCT01007435.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, Free University and Humboldt University of Berlin, Berlin, Germany.
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Burmester
authors.affiliation: Department of Medicine-Rheumatology, Dartmouth-Hitchcock Medical Center and Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USA.
authors.forename: William F
authors.initials: WF
authors.lastname: Rigby
authors.affiliation: Department of Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Ronald F
authors.initials: RF
authors.lastname: van Vollenhoven
authors.affiliation: Rheumatology Center, University of Massachusetts Medical School and UMass Memorial Medical Center, Worcester, Massachusetts, USA.
authors.forename: Jonathan
authors.identifier: http://orcid.org/0000-0002-8970-4260
authors.initials: J
authors.lastname: Kay
authors.affiliation: Department of Internal Medicine I, University of Cologne, Cologne, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rubbert-Roth
authors.affiliation: Genentech, South San Francisco, California, USA.
authors.forename: Ariella
authors.initials: A
authors.lastname: Kelman
authors.affiliation: Roche Products Ltd., Welwyn Garden City, UK.
authors.forename: Sophie
authors.initials: S
authors.lastname: Dimonaco
authors.affiliation: Roche Products Ltd., Welwyn Garden City, UK.
authors.forename: Nina
authors.initials: N
authors.lastname: Mitchell
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D012074:Remission Induction; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab; D008727:Methotrexate
keywords: DMARDs (biologic); Early Rheumatoid Arthritis; Methotrexate