Clinical pharmacology of tocilizumab for the treatment of polyarticular-course juvenile idiopathic arthritis

ABSTRACT

Introduction: The efficacy and safety of tocilizumab (TCZ), a humanized anti–interleukin-6 receptor (IL-6R) monoclonal antibody, in patients with polyarticular-course juvenile idiopathic arthritis (pJIA) were demonstrated in clinical trials.

Area covered: A literature search was undertaken in the public domain from 1995 to 2016. Data included in the regulatory submission leading to approval of TCZ for the treatment of pJIA in the European Union, United States, and Japan were also presented. TCZ 10 mg/kg in patients weighing <30 kg provided pharmacokinetic exposure comparable to that of TCZ 8 mg/kg for patients ≥30 kg. Pharmacodynamic (C-reactive protein, erythrocyte sedimentation rate, IL-6, and soluble IL-6R) and efficacy outcomes were comparable between TCZ 10 mg/kg in patients <30 kg and TCZ 8 mg/kg in patients ≥30 kg. Proportions of patients achieving JIA ACR 30/50/70/90 responses at week 16 increased with higher exposure (mean±SD C_min from quartile 1 to quartile 4: 0.02 ± 0.047, 0.98 ± 0.707, 5.00 ± 1.73, and 16.54 ± 7.74 µg/mL; n = 42). The adverse event rate did not increase with increased exposure. Data support weight–based dosing regimens.

Expert commentary: Biologics have improved outcomes for patients with pJIA with inadequate response to conventional therapy. TCZ will likely become an increasingly important treatment option for the management of pJIA.

KEYWORDS:

• Clinical pharmacology
• C-reactive protein
• exposure–response relationship
• interleukin-6
• interleukin-6 receptor
• pharmacokinetics
• polyarticular-course juvenile idiopathic arthritis
• tocilizumab

Declaration of interest

X Zhang was an employee of Hoffmann-La Roche Inc. at the time the work was performed. YC Chen is an employee of Hoffmann-La Roche Inc. K Terao is an employee of Chugai Pharmaceutical Co. 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. Editorial support was provided by ApotheCom, a Huntsworth Health company and funded by Hoffmann-La Roche Inc.

Authors’ note

With regard to the unpublished data (cited as data on file), all results are final and were submitted to regulatory agencies as part of licensing approval.

Additional information

Funding

This manuscript was funded by the sponsor Hoffmann-La Roche Inc.