Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial

Lancet. 2008 Mar 22;371(9617):998-1006. doi: 10.1016/S0140-6736(08)60454-7.


Background: Systemic-onset juvenile idiopathic arthritis does not always respond to available treatments, including antitumour necrosis factor agents. We investigated the efficacy and safety of tocilizumab, an anti-interleukin-6-receptor monoclonal antibody, in children with this disorder.

Methods: 56 children (aged 2-19 years) with disease refractory to conventional treatment were given three doses of tocilizumab 8 mg/kg every 2 weeks during a 6-week open-label lead-in phase. Patients achieving an American College of Rheumatology Pediatric (ACR Pedi) 30 response and a C-reactive protein concentration (CRP) of less than 5 mg/L were randomly assigned to receive placebo or to continue tocilizumab treatment for 12 weeks or until withdrawal for rescue medication in a double-blind phase. The primary endpoint of the double-blind phase was an ACR Pedi 30 response and CRP concentration of less than 15 mg/L. Patients responding to tocilizumab and needing further treatment were enrolled in an open-label extension phase for at least 48 weeks. The analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, numbers NCT00144599 (for the open-label lead-in and double-blind phases) and NCT00144612 (for the open-label extension phase).

Findings: At the end of the open-label lead-in phase, ACR Pedi 30, 50, and 70 responses were achieved by 51 (91%), 48 (86%), and 38 (68%) patients, respectively. 43 patients continued to the double-blind phase and were included in the efficacy analysis. Four (17%) of 23 patients in the placebo group maintained an ACR Pedi 30 response and a CRP concentration of less than 15 mg/L compared with 16 (80%) of 20 in the tocilizumab group (p<0.0001). By week 48 of the open-label extension phase, ACR Pedi 30, 50, and 70 responses were achieved by 47 (98%), 45 (94%), and 43 (90%) of 48 patients, respectively. Serious adverse events were anaphylactoid reaction, gastrointestinal haemorrhage, bronchitis, and gastroenteritis.

Interpretation: Tocilizumab is effective in children with systemic-onset juvenile idiopathic arthritis. It might therefore be a suitable treatment in the control of this disorder, which has so far been difficult to manage.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Arthritis, Juvenile / drug therapy*
  • Arthritis, Juvenile / physiopathology
  • C-Reactive Protein / drug effects
  • C-Reactive Protein / metabolism
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Japan
  • Male
  • Receptors, Interleukin-6 / antagonists & inhibitors
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Receptors, Interleukin-6
  • C-Reactive Protein
  • tocilizumab

Associated data

  • ClinicalTrials.gov/NCT00144599
  • ClinicalTrials.gov/NCT00144612