Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, Korea.
Department of Pediatrics, Eulji University School of Medicine, Daejeon, Korea.
Gut Liver. 2021 Jul 15;15(4):588-598. doi: 10.5009/gnl20134.
BACKGROUND/AIMS: Anti-drug antibodies (ADAs) can develop during treatment with anti-tumor necrosis factor (TNF) agents. We aimed to investigate the factors associated with immunogenicity of anti-TNF agents in pediatric patients with inflammatory bowel disease (IBD) and observe the clinical course of ADA-positive patients.
Pediatric IBD patients receiving maintenance treatment with anti-TNF agents who had been tested for ADAs against infliximab (IFX) or adalimumab (ADL) were included in this crosssectional study. Factors associated with ADA positivity were investigated by analyzing clinicodemographic, laboratory, and treatment-related factors.
A total of 76 patients (Crohn's disease, 65; ulcerative colitis, 11) were included. Among these, 59 and 17 patients were receiving IFX and ADL, respectively. ADAs were found in 10 patients (13.2%), all of whom were receiving IFX. According to multivariable logistic regression analysis, the IFX trough level (TL) was associated with ADA positivity (odds ratio, 0.25; 95% confidence interval [CI], 0.08 to 0.51; p=0.002). According to the receiver operating characteristic analysis, the optimal cutoff of the IFX TLs for stratifying patients based on the presence of ADAs against IFX was 1.88 μg/mL (area under curve, 0.941; 95% CI, 0.873 to 1.000; sensitivity, 80.0%; specificity, 95.9%; p<0.001). Among the 10 patients with ADAs against IFX, five patients (50%) switched to ADL within 1 year, while five patients (50%) kept receiving IFX. Transient ADAs were observed in three patients (30%).
IFX TL was the only factor associated with ADA formation in pediatric IBD patients receiving IFX. Future studies based on serial and proactive therapeutic drug monitoring are required in the future.
背景/目的：抗肿瘤坏死因子（TNF）药物治疗过程中会产生抗药物抗体（ADAs）。本研究旨在探讨儿科炎症性肠病（IBD）患者接受 TNF 拮抗剂治疗时发生免疫原性的相关因素，并观察 ADA 阳性患者的临床病程。
本横断面研究纳入了接受 TNF 拮抗剂维持治疗且检测过英夫利昔单抗（IFX）或阿达木单抗（ADL）ADA 的儿科 IBD 患者。通过分析临床、实验室和治疗相关因素，探讨 ADA 阳性的相关因素。
共纳入 76 例患者（克罗恩病 65 例，溃疡性结肠炎 11 例），其中 59 例和 17 例患者分别接受 IFX 和 ADL 治疗。10 例（13.2%）患者 ADA 阳性，均接受 IFX 治疗。多变量逻辑回归分析显示，IFX 谷浓度（TL）与 ADA 阳性相关（比值比，0.25；95%置信区间 [CI]，0.08 至 0.51；p=0.002）。根据受试者工作特征（ROC）分析，基于 ADA 对 IFX 的存在对 IFX TL 分层的最佳截断值为 1.88 μg/mL（曲线下面积，0.941；95%CI，0.873 至 1.000；敏感性，80.0%；特异性，95.9%；p<0.001）。10 例 ADA 阳性的 IFX 患者中，5 例（50%）在 1 年内转为 ADL，5 例（50%）继续接受 IFX 治疗。3 例（30%）患者 ADA 一过性出现。
IFX TL 是儿科 IBD 患者接受 IFX 治疗时发生 ADA 形成的唯一相关因素。未来需要基于连续和主动的治疗药物监测进行进一步研究。
