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

Abstract

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.

• Authors: Shumpei Yokota, Tomoyuki Imagawa, Masaaki Mori, Takako Miyamae, Yukoh Aihara, Shuji Takei, Naomi Iwata, Hiroaki Umebayashi, Takuji Murata, Mari Miyoshi, Minako Tomiita, Norihiro Nishimoto, Tadamitsu Kishimoto
• Journal: Lancet (London, England) (Lancet) Vol. 371 Issue 9617 Pg. 998-1006 (Mar 22 2008) ISSN: 1474-547X [Electronic] England
• PMID: 18358927 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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