Pharmacokinetic and Pharmacodynamics of Canakinumab in Patients with Systemic Juvenile Idiopathic Arthritis

The pharmacokinetics and pharmacodynamic (PD) properties of a monoclonal antibody, canakinumab, in pediatric patients with systemic juvenile idiopathic arthritis are presented. Blood samples were obtained from 4 phase II/III clinical studies in patients with SJIA. Canakinumab pharmacokinetics and total IL-1β kinetics were characterized by a population-based pharmacokinetic-binding model. Upon administration, canakinumab increased total-IL-1β complex in SJIA patients. Canakinumab clearance and volume of distribution were not impacted by age in pediatric patients after correction for the patient’s body weight. The estimated serum clearance of canakinumab (CLD) was 0.106 ± 0.00689 L/day, with a corresponding volume of distribution at steady state (Vss) of 3.2 L and an estimated half-life (T1/2) of 22 days, based on a model typical body weight of 33 kg. Body-weight-based dosing provided comparable canakinumab exposure across the age groups in patients from 2-