Population Pharmacokinetics Analysis of Infliximab in up to 10-Year-Old Patients with Paediatric Inflammatory Bowel Disease: Label-Recommended Dose Fails to Achieve Therapeutic Target Concentration

BACKGROUND AND OBJECTIVES: Younger patients with paediatric inflammatory bowel disease (IBD) may require higher infliximab (IFX) doses to attain similar target trough levels compared with older paediatric and adult patients with IBD. This study aimed to investigate the population pharmacokinetics (popPK) of infliximab (IFX) in young paediatric patients with inflammatory bowel disease (IBD) (≤ 10 years old), optimize the IFX dosage in this special population and explore whether different IFX assays were comparable. METHODS: IFX therapeutic drug monitoring (TDM) data from young paediatric patients with IBD (≤ 10 years old) were retrospectively collected from 14 European and Canadian centres (2015-2019). External validation of published popPK models was performed by calculating relative mean predictive errors (rMPE) and relative root mean square errors (rRMSE) to assess bias and imprecision. A refined popPK model was then developed using nonlinear mixed-effects modelling in NONMEM version 7.4. PopPK parameters in young paediatric patients with IBD (≤ 10 years old) were compared with those in published paediatric patients (> 10 to < 17 years) and adults. RESULTS: ) remained similar (P > 0.05). With label-recommended dosing, IFX concentrations dropped below 5 mg/L for approximately 4 weeks during maintenance. CONCLUSIONS: Paediatric patients ≤ 10 years, demonstrated a higher IFX CL than paediatric patients > 10 to < 17 years and adults, with albumin and CRP explaining the variability of CL. The differences obtained across the IFX assays did not affect overall drug exposure. To maintain trough concentrations above 5 mg/L in paediatric patients ≤ 10 years, a dosing interval of 4 weeks is required.