Clinical and Biochemical Factors Associated with Infliximab Pharmacokinetics in Paediatric Patients with Inflammatory Bowel Disease

Abstract

Monitoring infliximab (IFX) concentrations is crucial for optimizing IFX therapy in children with inflammatory bowel diseases (IBDs) who show low response rates due to inadequate drug exposure. Substantial variation occurs in IFX trough concentrations in paediatric patients. Objectives: This study aimed to investigate IFX pharmacokinetics (PK) in children with IBD during both the induction phase and maintenance phases and to identify covariates associated with IFX PK. Methods: This single-centre retrospective cohort study was conducted at an academic children's hospital. Data was extracted from paediatric IBD patients receiving IFX between January 2018 and October 2023 and included demographic-, clinical- and laboratory parameters collected from electronic health records. Linear mixed model analysis was performed to investigate associations between these parameters and IFX trough concentrations. Target attainment [≥15 μg/mL in induction or 5-10 μg/mL in maintenance phase] of the IFX dosing regimens was evaluated. Results and Conclusions: A total of 115 children (417 unique IFX concentrations) were included. Multivariate analysis revealed significant positive associations between IFX and albumin concentrations (β = 0.388, p = 0.010) and IFX concentrations with dose (β = 6.534, p < 0.001), and an inversion association between IFX concentrations and treatment phase (β = -4.922, p < 0.001). During the induction and maintenance phases, 57.2% and 30.6% of IFX concentrations were subtherapeutic, respectively. A systematic search of studies investigating factors influencing IFX concentrations was concurrently performed. Our findings were critically compared against existing literature to assess relevant clinical and biochemical determinants of IFX PK in children with IBD. Our findings highlight the need for personalized dosing strategies in pediatric IBD patients, particularly during the induction phase. By implementing therapeutic drug monitoring (TDM) and considering clinical and biochemical factors, clinicians can implement more personalized strategies, potentially improving treatment efficacy and reducing the risk of treatment failure or adverse effects. This approach could lead to better target attainment, potentially enhancing clinical outcomes and minimizing premature switching to other therapies.

Keywords: covariates; inflammatory bowel disease; infliximab; paediatric; pharmacokinetics.

Figure 1

Flow diagram for patient selection in the retrospective study from January 2018 until October 2023. IFX: infliximab; IBD: inflammatory bowel disease.

Figure 2

Relationships between albumin levels, treatment phase, dosage, and IFX concentrations (µg/mL). (A) shows albumin concentrations (g/L) compared between sub-, therapeutic-, and supratherapeutic ranges of IFX concentrations. (B) shows IFX concentrations compared between induction and maintenance phases, showing significantly lower levels during maintenance compared to induction. (C) shows IFX concentrations compared across different IFX doses (5 mg/kg, 10 mg/kg, 15 mg/kg), with an expected dose-dependent increase in average IFX concentrations. The boxes represent the interquartile range (IQR), and the whiskers extend to 1.5 times the IQR from the first (lower end) and third (higher end) quartiles. The bars and 95% confidence intervals are based on the estimated marginal means and its confidence intervals, derived from linear mixed models (LMMs). * indicates p < 0.05, *** indicates p < 0.001.