Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Hospital for Sick Children, Toronto, ON, Canada.
Inflamm Bowel Dis. 2019 Jan 1;25(1):150-155. doi: 10.1093/ibd/izy217.
There is some evidence in adults that higher serum infliximab (IFX) levels are needed to adequately treat fistulizing perianal Crohn's disease (CD). However, data in children are lacking. We aimed to determine postinduction serum trough IFX levels that are associated with healing of fistulizing perianal CD (PCD) at week 24.
In a multicenter inception cohort study, consecutive children younger than age 17 years with fistulizing perianal CD treated with IFX between April 2014 and June 2017 who had serum trough IFX titers measured before the fourth infusion were included. Area under the receiver operating characteristic curve (AUROC) was calculated to determine the best cutoff to predict fistula healing.
A total of 667 children with Crohn's disease were recruited, with 85 (12.7%) patients diagnosed with fistulizing PCD. There were 27 of 52 (52%) children in whom pre-fourth infusion IFX levels were measured (mean age, 12.57 ± 5.12 years). At week 24, 14 of 27 (52%) patients responded with healing/healed PCD, whereas the rest had ongoing active fistulizing disease. The median IFX pre-fourth dose level in the responders was 12.7 ug/mL, compared with 5.4 ug/mL in the active disease group (P = 0.02). There was a strong correlation between IFX levels and healing of fistulizing PCD at week 24 (r = 0.65; P < 0.001). The AUROC was 0.80 (95% confidence interval, 0.64-0.97; P = 0.007) for pre-fourth IFX level to predict response of fistulizing PCD at week 24, and a level of 12.7 ug/mL best predicted fistula healing.
Higher trough IFX levels are associated with healing of fistulizing perianal CD.
有证据表明，成人患者需要更高的血清英夫利昔单抗（IFX）水平才能充分治疗瘘管性肛周克罗恩病（CD）。然而，儿童的数据却很缺乏。我们旨在确定诱导后血清 IFX 谷值水平与第 24 周瘘管性肛周 CD（PCD）愈合的关系。
在一项多中心的入组队列研究中，纳入了 2014 年 4 月至 2017 年 6 月期间接受 IFX 治疗的瘘管性肛周 CD 且在第四次输注前测量了血清 IFX 滴度的年龄小于 17 岁的连续儿童患者。计算了受试者工作特征曲线（ROC）下面积（AUROC），以确定预测瘘管愈合的最佳截断值。
共纳入 667 例克罗恩病患儿，其中 85 例（12.7%）患儿被诊断为瘘管性 PCD。在 52 例患儿（52%）中测量了第四次输注前 IFX 水平，这些患儿的平均年龄为 12.57 ± 5.12 岁。在第 24 周时，27 例患儿中有 14 例（52%）对治疗有反应，瘘管性 PCD 愈合/治愈，而其余患儿的瘘管性疾病仍处于活动期。有反应者的中位 IFX 第四次剂量前水平为 12.7ug/mL，而活动期疾病组为 5.4ug/mL（P=0.02）。IFX 水平与第 24 周瘘管性 PCD 的愈合之间存在很强的相关性（r=0.65；P<0.001）。第 24 周 IFX 第四次前水平预测瘘管性 PCD 反应的 AUROC 为 0.80（95%置信区间，0.64-0.97；P=0.007），12.7ug/mL 水平可最好地预测瘘管愈合。
更高的 IFX 谷值水平与瘘管性肛周 CD 的愈合有关。
