Department of Gastroenterology, Sheba Medical Center.
Pediatric Gastroenterology Unit, Edmond & Lily Safra Children's Hospital.
J Pediatr Gastroenterol Nutr. 2018 Oct;67(4):507-512. doi: 10.1097/MPG.0000000000002051.
While infliximab pharmacokinetics are associated with therapy outcome in adult inflammatory bowel disease (IBD) population, limited data are available in pediatric patients. We aimed to define the relationship between infliximab trough and antibodies' levels (IFX-TL, ATI) and clinical, biomarker remission.
IFX-TL and ATI were routinely obtained between 2011 and 2017. Associations with clinical and inflammatory (C-reactive protein, CRP) end-points were studied throughout the first year of infliximab therapy.
A total of 63 patients (50 Crohn disease, 13 ulcerative colitis, median follow-up 16 months, median 8 samples/patient) were included, and 773 sera-samples were analyzed. Sera of patients in clinical remission had higher median IFX-TLs than sera of those with active disease (4 vs 2.25 μg/mL, P < 0.0001). In addition, patients with normal CRP had a higher median IFX-TL than those with elevated CRP (P = 0.02). Moreover, IFX-TL > 9.2 μg/mL at week 2 predicted clinical remission by week 14 (sensitivity 71.4%, specificity 81.2%, area under curve (AUC) = 0.73, P = 0.02) and IFX-TL > 2.2 μg/mL at week 6 predicted infliximab retention beyond 1 year of treatment (sensitivity 88.9%, specificity 100.0%, AUC = 0.974, P < 0.0001).
A significant association between IFX-TL and ATI and clinical and biomarker remission status in pediatric IBD patients was demonstrated, including a temporal association between week 2, 6 levels and outcome of induction and between week 6 and 14 levels and remission at 1 year of therapy. These findings suggest that therapeutic drug monitoring may be considered for management guidance among pediatric IBD patients.
英夫利昔单抗药代动力学与成人炎症性肠病（IBD）患者的治疗效果相关，然而在儿科患者中相关数据有限。我们旨在确定英夫利昔单抗谷浓度（IFX-TL）和抗体水平（ATI）与临床、生物标志物缓解之间的关系。
2011 年至 2017 年期间常规检测 IFX-TL 和 ATI。在英夫利昔单抗治疗的第一年中，研究了这些指标与临床和炎症（C 反应蛋白，CRP）终点的关联。
共纳入 63 例患者（50 例克罗恩病，13 例溃疡性结肠炎，中位随访 16 个月，中位 8 个样本/患者），分析了 773 份血清样本。处于临床缓解的患者血清 IFX-TL 中位数高于处于活动期疾病的患者（4 与 2.25μg/ml，P＜0.0001）。此外，CRP 正常的患者 IFX-TL 中位数高于 CRP 升高的患者（P=0.02）。此外，第 2 周 IFX-TL＞9.2μg/ml 预测第 14 周达到临床缓解（敏感性 71.4%，特异性 81.2%，曲线下面积（AUC）为 0.73，P=0.02），第 6 周 IFX-TL＞2.2μg/ml 预测治疗 1 年后继续使用英夫利昔单抗（敏感性 88.9%，特异性 100.0%，AUC 为 0.974，P＜0.0001）。
在儿科 IBD 患者中，IFX-TL 和 ATI 与临床和生物标志物缓解状态之间存在显著关联，包括第 2、6 周水平与诱导治疗效果之间的时间关联，以及第 6、14 周水平与治疗 1 年时的缓解之间的关联。这些发现表明，治疗药物监测可能被认为是儿科 IBD 患者管理指导的一种方法。
