Clinical pharmacology of tocilizumab for the treatment of systemic juvenile idiopathic arthritis

Abstract

Tocilizumab is a humanized anti-IL-6 receptor monoclonal antibody approved for the treatment of rheumatoid arthritis and systemic juvenile idiopathic arthritis. Biweekly doses of 8 mg/kg for patients who weigh ≥30 kg and 12 mg/kg for patients who weigh <30 kg produce adequate blockade of IL-6 receptors and normalization of C-reactive protein levels. The mean area under the curve during a 2-week dosing interval, maximum and minimum serum concentrations for both doses were 1341 ± 415 µg·day/ml, 245 ± 57.2 and 57.5 ± 23.3 µg/ml, respectively. Tocilizumab pharmacokinetic exposure parameters and clinical end points were comparable between these two dose groups. Proportions of patients achieving clinical end points were comparable across exposure quartiles, suggesting that pharmacokinetic exposures are within the plateau of the exposure–response curve.

Keywords::

• Actemra^®
• clinical pharmacology
• C-reactive protein
• exposure–response relationship
• IL-6
• IL-6 receptor
• pharmacokinetics
• systemic juvenile idiopathic arthritis
• tocilizumab

Authors’ note

With regard to currently unpublished pharmacology data throughout this article, all results are final and have been submitted to regulatory agencies as part of licensing approval.

Financial & competing interests disclosure

X Zhang and PN Morcos are, or were at the time of the study, employees of Hoffmann-La Roche Inc. T Saito and K Terao are employees of Chugai Pharmaceutical Co., Ltd. This manuscript was funded by Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

The authors thank Mark English and Susan Quiñones (both Roche employees) for their editorial assistance with the manuscript, which was funded by Roche.