TY - JOUR
T1 - Population Pharmacokinetics of Infliximab in Children with Juvenile Idiopathic Arthritis
AU - Nassar-Sheikh Rashid, Amara
AU - Schonenberg-Meinema, Dieneke
AU - Berends, Sophie E.
AU - van den Berg, J. Merlijn
AU - Mathôt, Ron A. A.
N1 - Publisher Copyright: © 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - BACKGROUND: The recommended infliximab (IFX) dose in (pediatric) rheumatology practice is 3-6 mg/kg every 4-8 weeks. Higher dosage regimens (>10 mg/kg) of IFX are effective and safe. To optimize IFX treatment in patients with juvenile idiopathic arthritis (JIA), therapeutic drug monitoring might be beneficial. To support routine therapeutic drug monitoring of IFX and regimen optimization for patients with JIA, in-depth knowledge of the pharmacokinetic (PK) variability of IFX is needed. As soon as the optimal therapeutic drug ranges are known, PK model-based simulation can be used to individualize drug dosing recommendations. In this study, a population PK model for IFX is described for patients with JIA. METHODS: Data including IFX trough concentrations and anti-IFX antibodies of 27 pediatric patients with JIA on IFX maintenance treatment were retrieved from electronic charts. Three population PK models from the literature were validated for the authors' data set using the nonlinear mixed-effects modeling program NONMEM. A novel population PK model was developed based on the study data. RESULTS: A total of 65 blood samples obtained after a median of 32 days after the last IFX infusion (interquartile range 28-42) were analyzed. The 3 published models underpredicted the observed trough concentrations. A newly developed one-compartment model best described the data corresponding to IFX serum concentration over time in patients with JIA. CONCLUSIONS: This study shows a novel PK model for IFX in patients with JIA. The data show that different PK models are needed for different age categories (children or adults) and different diseases.
AB - BACKGROUND: The recommended infliximab (IFX) dose in (pediatric) rheumatology practice is 3-6 mg/kg every 4-8 weeks. Higher dosage regimens (>10 mg/kg) of IFX are effective and safe. To optimize IFX treatment in patients with juvenile idiopathic arthritis (JIA), therapeutic drug monitoring might be beneficial. To support routine therapeutic drug monitoring of IFX and regimen optimization for patients with JIA, in-depth knowledge of the pharmacokinetic (PK) variability of IFX is needed. As soon as the optimal therapeutic drug ranges are known, PK model-based simulation can be used to individualize drug dosing recommendations. In this study, a population PK model for IFX is described for patients with JIA. METHODS: Data including IFX trough concentrations and anti-IFX antibodies of 27 pediatric patients with JIA on IFX maintenance treatment were retrieved from electronic charts. Three population PK models from the literature were validated for the authors' data set using the nonlinear mixed-effects modeling program NONMEM. A novel population PK model was developed based on the study data. RESULTS: A total of 65 blood samples obtained after a median of 32 days after the last IFX infusion (interquartile range 28-42) were analyzed. The 3 published models underpredicted the observed trough concentrations. A newly developed one-compartment model best described the data corresponding to IFX serum concentration over time in patients with JIA. CONCLUSIONS: This study shows a novel PK model for IFX in patients with JIA. The data show that different PK models are needed for different age categories (children or adults) and different diseases.
KW - JIA
KW - TDM
KW - infliximab
KW - population pharmacokinetic model
UR - http://www.scopus.com/inward/record.url?scp=85126830772&partnerID=8YFLogxK
U2 - https://doi.org/10.1097/FTD.0000000000000914
DO - https://doi.org/10.1097/FTD.0000000000000914
M3 - Article
C2 - 34292215
SN - 0163-4356
VL - 44
SP - 301
EP - 307
JO - Therapeutic drug monitoring
JF - Therapeutic drug monitoring
IS - 2
ER -