Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial
S Yokota, T Imagawa, M Mori, T Miyamae, Y Aihara… - The Lancet, 2008 - thelancet.com
S Yokota, T Imagawa, M Mori, T Miyamae, Y Aihara, S Takei, N Iwata, H Umebayashi…
The Lancet, 2008•thelancet.comBackground 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 …
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 …
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.
Funding
Chugai Pharmaceuticals.
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