Physiologically Based Pharmacokinetic/Pharmacodynamic Model for Secukinumab: Dose Exploration in Pediatric Patients with Plaque Psoriasis.

Abstract

Secukinumab has been widely applied in adults for the treatment of plaque psoriasis and psoriatic arthritis. However, there remains a knowledge gap in the dosing of secukinumab for pediatric patients with plaque psoriasis. This study aims to investigate the dosing regimen for pediatric patients aged 2 years and older. A physiologically based pharmacokinetic model for secukinumab was developed and validated in adult patients. Based on this model, two additional observation compartments for total interleukin-17A (IL-17A) and skin free IL-17A were incorporated to evaluate the inhibition of secukinumab on its targets. Ultimately, this model was extrapolated to pediatric patients. The model precisely captured the pharmacokinetic profiles and serum total IL-17A levels observed in different studies, encompassing various dosing schedules and formulations. Pediatric patients were stratified by weight, and the model incorporated age-related developmental factors. Using the inhibition of skin free IL-17A during steady-state treatment as a benchmark for a 300 mg adult dose indicates that pediatric patients weighing less than 25 kg require 75 mg, those weighing between 25 and 50 kg require 150 mg, and patients weighing more than 50 kg require 225 mg to achieve similar levels of inhibition. This conclusion provides new ideas for flexible medication use in pediatric patients with psoriasis.