Anti-tumor necrosis factor alpha (anti-TNFα) inhibitors are used extensively for the management of moderate to severe inflammatory bowel disease (IBD) in both adult and pediatric patients. Unfortunately, not all patients show an optimal response to induction therapy, while others lose their response over time for reasons yet poorly understood. We report on a pharmacokinetic/pharmacogenetic approach to monitor the therapy with anti-TNFα in a real-world cohort of seventy-nine pediatric patients affected by IBD that was analyzed retrospectively. We evaluated plasma concentrations of infliximab, adalimumab, and related anti-drug antibodies (ADAs), and single nucleotide polymorphisms (SNPs) in genes involved in immune processes and inflammation on the anti-TNFα response. We found a significant association between the SNP in TNFα promoter (−308G>A) and clinical remission without steroids in patients on infliximab therapy. Additionally, a potential connection between HLA-DQA1*05 genetic variant carriers and a higher risk of anti-TNFα immunogenicity emerged.

抗肿瘤坏死因子α（抗TNFα）抑制剂广泛用于治疗成人和儿童患者的中度至重度炎症性肠病（IBD）。不幸的是，并非所有患者都对诱导治疗表现出最佳反应，而另一些患者则随着时间的推移而失去反应，原因尚不清楚。我们报告了一种药代动力学/药物遗传学方法，用于监测现实世界中 79 名 IBD 儿科患者的抗 TNFα 治疗情况，并进行了回顾性分析。我们评估了英夫利昔单抗、阿达木单抗和相关抗药物抗体 (ADA) 的血浆浓度，以及参与免疫过程和炎症的基因中的单核苷酸多态性 (SNP) 对抗 TNFα 反应的影响。我们发现 TNFα 启动子中的 SNP (−308G>A) 与接受英夫利昔单抗治疗的患者无需类固醇的临床缓解之间存在显着相关性。此外，HLA-DQA1*05 遗传变异携带者与抗 TNFα 免疫原性较高风险之间存在潜在联系。