Factors that influence infliximab biosimilar trough levels in the pediatric inflammatory bowel disease population

The pharmacokinetics and pharmacodynamics of biosimilar infliximab (IFX-BioS) in pediatric inflammatory bowel disease (IBD) are poorly investigated. The aim of this study was to investigate factors predicting IFX-BioS trough levels (TLs). IBD children with an indication to start IFX-BioS were included in this prospective observational study (January 2021-June 2022). TLs were measured at the 4^th and 6^th infusions and correlated with several covariates. A total of 110 TLs in 55 children were included. The multivariate linear regression model at the 4^th infusion found a positive correlation between TLs and age at diagnosis (B:1.950, 95% CI: [0.019, 3.882], <i>p</i> = 0.048) and IFX-BioS dose/kg (B:1.962, 95% CI: [0.238, 3.687], <i>p</i> = 0.029), and a negative correlation with clinical scores (B:-0.401, 95% CI: [−0.738, −0.064], <i>p</i> = 0.023). At the 6^th infusion, female gender (B:6.887, 95% CI: [0.861, 12.913], <i>p</i> = 0.029), hemoglobin (B:1.853, 95% CI: [0.501, 3.204], <i>p</i> = 0.011), and IFX-BioS dose/kg (B:1.792, 95% CI: [0.979, 2.605], <i>p</i> &lt; 0.001) were found to be positively correlated to TLs. No association between combined clinical and biochemical remission and TLs was found. This study discovered some predictors for IFX-BioS TLs in IBD children. Knowledge of predictive factors could help physicians choose the best dosing regimen.

目前关于生物类似药英夫利昔单抗（infliximab, IFX-BioS）在儿童炎症性肠病（pediatric inflammatory bowel disease, IBD）中的药代动力学与药效学特征，相关研究尚较为匮乏。本研究旨在探究可预测英夫利昔单抗生物类似药谷浓度（trough levels, TLs）的影响因素。本前瞻性观察性研究（2021年1月至2022年6月）纳入存在英夫利昔单抗生物类似药用药指征的炎症性肠病患儿，于第4次及第6次输注时检测其谷浓度，并将检测结果与多项协变量进行相关性分析。最终共纳入55名患儿的110份谷浓度检测数据。第4次输注时的多元线性回归模型结果显示，谷浓度与诊断时年龄（回归系数B=1.950，95%置信区间（confidence interval, CI）：[0.019, 3.882]，p=0.048）、英夫利昔单抗生物类似药每公斤体重给药剂量（B=1.962，95%CI：[0.238, 3.687]，p=0.029）呈正相关，与临床评分呈负相关（B=-0.401，95%CI：[-0.738, -0.064]，p=0.023）。第6次输注时的分析结果显示，女性性别（B=6.887，95%CI：[0.861, 12.913]，p=0.029）、血红蛋白水平（B=1.853，95%CI：[0.501, 3.204]，p=0.011）以及英夫利昔单抗生物类似药每公斤体重给药剂量（B=1.792，95%CI：[0.979, 2.605]，p<0.001）与谷浓度呈正相关。本研究未发现临床与生化联合缓解状态与谷浓度存在显著关联。本研究明确了儿童炎症性肠病患儿体内英夫利昔单抗生物类似药谷浓度的多项预测因子，掌握这些预测因素可协助临床医师优化给药方案。