From the Pediatric Gastroenterology Institute, "Dana-Dwek" Children's Hospital, Tel Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
the Department of Pediatric Gastroenterology, Hepatology and Nutrition, Hospital Sant Joan de Déu, Barcelona, Spain.
J Pediatr Gastroenterol Nutr. 2022 Dec 1;75(6):717-723. doi: 10.1097/MPG.0000000000003608. Epub 2022 Sep 8.
Escalation of the ustekinumab (UST) maintenance dosage was effective in adults with Crohn disease (CD), but no data are available for children. We evaluated the effectiveness and safety of dose escalation of UST in pediatric CD.
This was a retrospective multicenter study from 25 centers affiliated with the IBD Interest and Porto groups of ESPGHAN. We included children with CD who initiated UST at a standard dosing and underwent either dose escalation to intervals shorter than 8 weeks or re-induction of UST due to active disease. Demographic, clinical, laboratory, endoscopic, imaging, and safety data were collected up to 12 months of follow-up.
Sixty-nine children were included (median age 15.8 years, interquartile range 13.8-16.9) with median disease duration of 4.3 years (2.9-6.3). Most children were biologic (98.6%)- and immunomodulator (86.8%)- experienced. Clinical response and remission were observed at 3 months after UST escalation in 46 (67%) and 29 (42%) children, respectively. The strongest predictor for clinical remission was lower weighted Pediatric Crohn Disease Activity Index (wPCDAI) at escalation ( P = 0.001). The median C-reactive protein level decreased from 14 (3-28.03) to 5 (1.1-20.5) mg/L ( P = 0.012), and the fecal calprotectin level from 1100 (500-2300) to 515 (250-1469) µg/g ( P = 0.012) 3 months post-escalation. Endoscopic and transmural healing were achieved in 3 of 19 (16%) and 2 of 15 (13%) patients, respectively. Thirteen patients (18.8%) discontinued therapy due to active disease. No serious adverse events were reported.
Two-thirds of children with active CD responded to dose escalation of UST. Milder disease activity may predict a favorable outcome following UST dose escalation.
乌司奴单抗（UST）维持剂量的升级在克罗恩病（CD）成人患者中是有效的，但儿童患者的数据尚不清楚。我们评估了 UST 在儿科 CD 患者中的剂量升级的有效性和安全性。
这是一项来自 25 家隶属于 ESPGHAN 的 IBD 兴趣和波尔图组织的多中心回顾性研究。我们纳入了起始 UST 标准剂量且接受 UST 剂量升级（间隔短于 8 周）或因疾病活动而重新开始 UST 治疗的 CD 患儿。收集了患者在随访 12 个月内的人口统计学、临床、实验室、内镜、影像学和安全性数据。
共纳入 69 例患儿（中位年龄 15.8 岁，四分位间距 13.8-16.9），中位疾病病程为 4.3 年（2.9-6.3）。大多数患儿曾接受生物制剂（98.6%）和免疫调节剂（86.8%）治疗。UST 升级后 3 个月时，46 例（67%）和 29 例（42%）患儿分别出现临床缓解和临床缓解。升级时较低的加权儿科克罗恩病活动指数（wPCDAI）是临床缓解的最强预测因素（P=0.001）。C 反应蛋白水平从 14（3-28.03）降至 5（1.1-20.5）mg/L（P=0.012），粪便钙卫蛋白水平从 1100（500-2300）降至 515（250-1469）µg/g（P=0.012）。19 例患儿中有 3 例（16%）内镜下和透壁愈合，15 例患儿中有 2 例（13%）内镜下和透壁愈合。13 例患儿（18.8%）因疾病活动而停药。未报告严重不良事件。
在活动性 CD 患儿中，有三分之二对 UST 剂量升级有反应。较轻的疾病活动度可能预示着 UST 剂量升级后有较好的结局。
