Department of Medicine, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH, 5229, USA.
Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Curr Gastroenterol Rep. 2023 Nov;25(11):323-332. doi: 10.1007/s11894-023-00895-4. Epub 2023 Sep 11.
This review focuses on recent advancements in anti-TNF therapeutic drug monitoring (TDM), pharmacogenetics and personalized drug selection for children with inflammatory bowel disease (IBD).
Several real-world studies and one clinical trial in children have demonstrated that proactive TDM, targeting higher exposure concentrations (> 5 µg/mL), can improve disease remission rates and enhance durability of the anti-TNF biologics. Recent data from both adult and pediatric IBD patients have revealed an association between a genetic polymorphism (HLA-DQA1*05) and the development of auto-drug antibodies. The impact of this association on clinical outcomes, considering more routine use proactive TDM and dose optimization in children, is still under investigation. Additionally, recent studies have identified potential inflammatory signatures and biomarkers that may serve as companion diagnostics for anti-TNF biologics. The effective management of anti-TNF therapies in children with IBD requires evidence-based precision dosing strategies, including routine TDM and proactive pharmacodynamic assessments.
重点介绍炎症性肠病（IBD）儿童抗 TNF 治疗药物监测（TDM）、药物遗传学和个体化药物选择方面的最新进展。
几项针对儿童的真实世界研究和一项临床试验表明，主动 TDM 靶向更高的暴露浓度（>5μg/ml），可以提高疾病缓解率并增强抗 TNF 生物制剂的持久性。来自成人和儿科 IBD 患者的最新数据显示，遗传多态性（HLA-DQA1*05）与自身抗体的产生之间存在关联。考虑到儿童中更常规地使用主动 TDM 和剂量优化，这种关联对临床结果的影响仍在研究中。此外，最近的研究还确定了潜在的炎症特征和生物标志物，它们可能作为抗 TNF 生物制剂的伴随诊断。IBD 儿童抗 TNF 治疗的有效管理需要基于证据的精准剂量策略，包括常规 TDM 和主动药效学评估。
