POS0070 POPULATION PHARMACOKINETICS OF INFLIXIMAB IN CHILDREN WITH JUVENILE IDIOPATHIC ARTHRITIS
Authors: A. Nassar-Sheikh Rashid, D. Schonenberg-Meinema, S. Berends, J. M. Van den Berg, R. Mathot
Journal: Annals of the Rheumatic Diseases (2021)

Background: Higher dosage regimes for Infliximab (IFX) have been described to be effective in partial- or non-responding adults and children with rheumatic disease and appear to be safe (1,2). To optimize IFX treatment in juvenile idiopathic arthritis (JIA) patients, therapeutic drug monitoring (TDM) might be beneficial. To support routine TDM of IFX and dose regimen optimization in JIA patients, more in-depth knowledge of the pharmacokinetic (PK) variability of IFX is needed. Ultimately, as soon as the optimal therapeutic drug ranges will be known, PK model-based simulation can be used to individualize drug dosing recommendations. Individual dosages may be adjusted by taking specific patient characteristics into account that explain inter-patient variability in pharmacokinetics (PK). Inter-patient variability can be quantified and investigated by the population approach. Objectives: Our hypothesis is that optimizing dosage and frequency of IFX administration for individual patients will improve treatment outcome. In this current study, the population PK for IFX are described for JIA patients. Methods: Data including IFX trough concentrations and anti-IFX antibodies of 27 JIA patients on IFX maintenance treatment were retrieved from electronic charts. Three population pharmacokinetic models from literature were validated for our dataset using nonlinear-mixed effects modeling program NONMEM (3,4,5). A novel population pharmacokinetic model was developed based on our study data. Results: A total of 65 obtained blood samples after a median of 32 days after the last IFX infusion (IQR 28-42) were analyzed. The three published models underpredicted the observed trough concentrations. A newly developed one compartment model best described the IFX serum concentration over time data in JIA patients (see Figure 1). Conclusion: Our study shows a novel and the first PK model for IFX in JIA patients. Our main finding was that a one- compartment model best described the IFX serum concentration over time data. Predictive performance of the known models from literature was insufficient for our patient data. Our data also show that different PK models are needed for different age categories (children or adults) and in different diseases. References: [1]Nozaki Y et al. Infliximab dose adjustment can improve the clinical and radiographic outcomes of rheumatoid arthritis patients: REVIVE study results. Biologics. 2018. [2]Tambralli A et al. High doses of infliximab in the management of juvenile idiopathic arthritis. J Rheumatol. 2013. [3]Fasanmade AA et al. Pharmacokinetic properties of infliximab in children and adults with Crohn’s disease: a retrospective analysis of data from 2 phase III clinical trials. Clin Ther. 2011. [4]Xu Z et al. Population pharmacokinetics of infliximab in patients with ankylosing spondylitis. J Clin Pharmacol. 2008. [5]Ternant D et al. Relationship between inflammation and infliximab pharmacokinetics in rheumatoid arthritis. Br J Clin Pharmacol. 2014. Table 1. Patient characteristics N=27 patients Weight (kg) 52 [40 – 62] BSA 1.6 [1.3 – 1.8] Age (years) 14 [11 – 17] Male, N (%) 6 (22%) CRP (mg/L) 0.5 [0.2 – 0.7] WBC count 6.5 [5.6 –7.5] Antibodies-to-IFX 1 (4%) Dose (mg) 300 [200-400] Dose (mg/kg) 5.4 [4.9 -7.0] Hemoglobine (mmol/L) 7.9 [7.5 -8.2] ESR (mm/h) 5 [5-8] Uveitis 3 (11%) Disclosure of Interests: None declared.