Van, Linh, Floch, David, Jiang, Xuemin, Klein, Ulf, Abrams, Ken and Sunkara, Gangadhar (2016) Pharmacokinetic and Pharmacodynamics of Canakinumab in Patients with Systemic Juvenile Idiopathic Arthritis. The Journal of Clinical Pharmacology, Online (0(0)). pp. 1-12. ISSN 10.1002/jcph:754

Abstract

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- <20 years with SJIA. In younger children, a modest increase in the turnover rate of IL-1β was observed. Compared to other indications, IL-1β production rate was higher and clearance was slower in patients with SJIA. Low immunogenicity incidence of 3.1% was observed and none of the patients had neutralizing antibodies. In conclusion, the PK/PD findings further support dose selection of canakinumab in patients with SJIA.

Item Type:	Article
Keywords:	canakinumab, systemic juvenile idiopathic arthritis, pharmacokinetics, pharmacodynamics, Pediatrics
Date Deposited:	12 Oct 2016 00:45
Last Modified:	12 Oct 2016 00:45
URI:	https://oak.novartis.com/id/eprint/28132