title: Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study.
abstract: BACKGROUND
  The anti-interleukin (IL) 6 receptor antibody tocilizumab inhibits signalling of IL6, a key cytokine in rheumatoid arthritis (RA) pathogenesis.
  
  
  OBJECTIVE
  To evaluate through the AMBITION study the efficacy and safety of tocilizumab monotherapy versus methotrexate in patients with active RA for whom previous treatment with methotrexate/biological agents had not failed.
  
  
  METHODS
  This 24-week, double-blind, double-dummy, parallel-group study, randomised 673 patients to either tocilizumab 8 mg/kg every 4 weeks, or methotrexate, starting at 7.5 mg/week and titrated to 20 mg/week within 8 weeks, or placebo for 8 weeks followed by tocilizumab 8 mg/kg. The primary end point was the proportion of patients achieving American College of Rheumatology (ACR) 20 response at week 24.
  
  
  RESULTS
  The intention-to-treat analysis demonstrated that tocilizumab was better than methotrexate treatment with a higher ACR20 response (69.9 vs 52.5%; p<0.001), and 28-joint Disease Activity Score (DAS28) <2.6 rate (33.6 vs 12.1%) at week 24. Mean high-sensitivity C-reactive protein was within the normal range from week 12 with tocilizumab, whereas levels remained elevated with methotrexate. The incidence of serious adverse events with tocilizumab was 3.8% versus 2.8% with methotrexate (p = 0.50), and of serious infections, 1.4% versus 0.7%, respectively. There was a higher incidence of reversible grade 3 neutropenia (3.1% vs 0.4%) and increased total cholesterol > or =240 mg/dl (13.2% vs 0.4%), and a lower incidence of alanine aminotransferase elevations >3x-<5x upper limit of normal (1.0% vs 2.5%), respectively.
  
  
  CONCLUSIONS
  Tocilizumab monotherapy is better than methotrexate monotherapy, with rapid improvement in RA signs and symptoms, and a favourable benefit-risk, in patients for whom treatment with methotrexate or biological agents has not previously failed.
authors.affiliation: Menzies Research Institute, University of Tasmania, Hobart, TAS 7001, Australia. g.jones@utas.edu.au
authors.forename: G
authors.initials: G
authors.lastname: Jones
authors.forename: A
authors.initials: A
authors.lastname: Sebba
authors.forename: J
authors.initials: J
authors.lastname: Gu
authors.forename: M B
authors.initials: MB
authors.lastname: Lowenstein
authors.forename: A
authors.initials: A
authors.lastname: Calvo
authors.forename: J J
authors.initials: JJ
authors.lastname: Gomez-Reino
authors.forename: D A
authors.initials: DA
authors.lastname: Siri
authors.forename: M
authors.initials: M
authors.lastname: Tomsic
authors.forename: E
authors.initials: E
authors.lastname: Alecock
authors.forename: T
authors.initials: T
authors.lastname: Woodworth
authors.forename: M C
authors.initials: MC
authors.lastname: Genovese
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015415:Biomarkers; D007166:Immunosuppressive Agents; D019947:Receptors, Interleukin-6; D002097:C-Reactive Protein; C502936:tocilizumab; D008727:Methotrexate