Department of Paediatric Gastroenterology, Erasmus MC-Sophia Children's Hospital, Rotterdam, Netherlands.
Department of Pediatrics, Ghent University Hospital, Ghent University, Ghent, Belgium.
J Pediatr Gastroenterol Nutr. 2024 Jul;79(1):62-75. doi: 10.1002/jpn3.12221. Epub 2024 May 2.
Paediatric and adult inflammatory bowel disease (pIBD, aIBD) patients may lose response to anti-tumour necrosis factor (TNF) treatment within the first year. Adult-extrapolated weight-based dosing is incorrect in children, due to age-related pharmacokinetic differences. We investigated biomarkers for initial and maintenance of response to infliximab (IFX) or adalimumab (ADA), comparing pIBD and aIBD patients.
In this prospective, observational study, pIBD (n = 24) and aIBD (n = 21) patients were included when initiating anti-TNF. Escalation from standard dosing and continued anti-TNF at 12 and 18 months were assessed. Biomarkers included clinical laboratory parameters, faecal calprotectin (FCP) and IFX trough levels (TLs). Plasma proteomics was performed in pIBD.
During our study, treatment escalation (in clinical loss of response) occurred more common in pIBD versus aIBD (p = 0.02). We established that IFX therapy escalation in pIBD patients was not due to low infliximab levels. We identified 9 pro-inflammatory proteins that were elevated in patients losing response.
Anti-TNF exposure-response relationship may be different in pIBD versus aIBD. No biomarkers for maintained response were identified, but 9 inflammatory proteins were of interest as potential predictors for loss of response in pIBD.
儿科和成人炎症性肠病（pIBD，aIBD）患者可能会在一年内对肿瘤坏死因子（TNF）治疗失去反应。由于年龄相关的药代动力学差异，儿童的成人外推体重剂量是不正确的。我们研究了英夫利昔单抗（IFX）或阿达木单抗（ADA）治疗起始和维持应答的生物标志物，比较了 pIBD 和 aIBD 患者。
在这项前瞻性、观察性研究中，当开始使用抗 TNF 时，纳入了 pIBD（n=24）和 aIBD（n=21）患者。评估了从标准剂量升级和在 12 个月和 18 个月时继续使用抗 TNF 的情况。生物标志物包括临床实验室参数、粪便钙卫蛋白（FCP）和 IFX 谷浓度（TL）。对 pIBD 患者进行了血浆蛋白质组学研究。
在我们的研究期间，pIBD 患者的治疗升级（临床治疗反应丧失）比 aIBD 更常见（p=0.02）。我们发现 pIBD 患者 IFX 治疗升级不是由于英夫利昔单抗水平低。我们确定了 9 种在失去反应的患者中升高的促炎蛋白。
pIBD 与 aIBD 相比，抗 TNF 暴露-反应关系可能不同。未确定维持反应的生物标志物，但 9 种炎症蛋白作为 pIBD 中反应丧失的潜在预测因子很有意义。
