Wang Ka Yu, Heikal Omnia Salah, van Rheenen Patrick F, Touw Daan J, Bourgonje Arno R, Mian Paola
Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands.
Department of Paediatric Gastroenterology, Hepatology and Nutrition, Beatrix Children's Hospital, University of Groningen, University Medical Centre Groningen, 9713 GZ Groningen, The Netherlands.
J Clin Med. 2025 Jan 27;14(3):845. doi: 10.3390/jcm14030845.
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. : 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. : 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. : 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, = 0.010) and IFX concentrations with dose (β = 6.534, < 0.001), and an inversion association between IFX concentrations and treatment phase (β = -4.922, < 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.
监测英夫利昔单抗（IFX）浓度对于优化炎症性肠病（IBD）患儿的IFX治疗至关重要，这些患儿因药物暴露不足而反应率较低。儿科患者的IFX谷浓度存在很大差异。本研究旨在调查IBD患儿在诱导期和维持期的IFX药代动力学（PK），并确定与IFX PK相关的协变量。这项单中心回顾性队列研究在一家学术儿童医院进行。数据从2018年1月至2023年10月接受IFX治疗的儿科IBD患者中提取，包括从电子健康记录中收集的人口统计学、临床和实验室参数。进行线性混合模型分析以研究这些参数与IFX谷浓度之间的关联。评估了IFX给药方案的目标达成情况[诱导期≥15μg/mL或维持期5-10μg/mL]。共纳入115名儿童（417个独特的IFX浓度）。多变量分析显示IFX与白蛋白浓度之间存在显著正相关（β = 0.388，P = 0.010），IFX浓度与剂量之间存在正相关（β = 6.534，P < 0.001），IFX浓度与治疗阶段之间存在负相关（β = -4.922，P < 0.001）。在诱导期和维持期，分别有57.2%和30.6%的IFX浓度低于治疗水平。同时对研究影响IFX浓度因素的研究进行了系统检索。将我们的研究结果与现有文献进行了严格比较，以评估IBD患儿IFX PK的相关临床和生化决定因素。我们的研究结果强调了在儿科IBD患者中采用个性化给药策略的必要性，特别是在诱导期。通过实施治疗药物监测（TDM）并考虑临床和生化因素，临床医生可以实施更个性化的策略，有可能提高治疗效果并降低治疗失败或不良反应的风险。这种方法可能会导致更好地实现目标，有可能改善临床结果并尽量减少过早改用其他疗法。
