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