Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics Mount Sinai, Icahn School of Medicine, 17 E. 102nd Street, Fifth Floor, New York, NY, 10029, USA.
Inflamm Bowel Dis. 2024 Nov 4;30(11):2057-2063. doi: 10.1093/ibd/izad300.
Upadacitinib (UPA) is a novel selective JAK inhibitor approved for adults with ulcerative colitis (UC) and with positive phase 3 data for Crohn's disease (CD). Pediatric off-label use is common due to delays in pediatric approvals; real-world data on UPA are needed to understand the safety and effectiveness in pediatric IBD.
This is a single-center retrospective case series study of adolescents (12-17 years) with inflammatory bowel disease IBD on UPA. The primary outcome was postinduction steroid-free clinical remission (SF-CR) defined as Pediatric UC Activity Index (PUCAI) or Pediatric CD Activity Index (PCDAI) ≤10. Secondary outcomes include postinduction clinical response (decrease ≥12.5 in PUCAI/PCDAI), postinduction C-reactive protein (CRP) normalization, 6-month SF-CR, and intestinal ultrasound response and remission. Adverse events were recorded through last follow-up.
Twenty patients (9 CD, 10 UC, 1 IBD-U; 55% female; median age 15 years, 90% ≥2 biologics) were treated with UPA for ≥12 weeks (median 51 [43-63] weeks). Upadacitinib was used as monotherapy in 55% and as combination with ustekinumab and vedolizumab in 35% and 10%, respectively. Week 12 SF-CR was achieved in 75% (15/20) and 80% (16/20) with CRP normalization. About 3/4 (14/19) achieved SF-CR at 6 months. Adverse event occurred in 2 patients (10%): Cytomegalovirus colitis requiring hospitalization and hyperlipidemia requiring no treatment. In the 75% with ultrasound monitoring, response and remission were achieved in 77% and 60%, respectively.
While awaiting pediatric registration trials, our data suggest that UPA is effective in inducing and maintaining SF-CR in adolescents with highly-refractory IBD with an acceptable safety profile.
Upadacitinib（UPA）是一种新型选择性 JAK 抑制剂，已获批准用于溃疡性结肠炎（UC）成人患者，并且在克罗恩病（CD）的 3 期临床试验中取得了阳性结果。由于儿科批准的延迟，儿科超适应证使用很常见；需要了解 UPA 在儿科 IBD 中的安全性和有效性的真实世界数据。
这是一项针对接受 UPA 治疗的青少年（12-17 岁）炎症性肠病（IBD）的单中心回顾性病例系列研究。主要结局是诱导后无类固醇的临床缓解（SF-CR），定义为儿童 UC 活动指数（PUCAI）或儿童 CD 活动指数（PCDAI）≤10。次要结局包括诱导后临床应答（PUCAI/PCDAI 下降≥12.5）、诱导后 C 反应蛋白（CRP）正常化、6 个月 SF-CR 以及肠超声应答和缓解。通过最后一次随访记录不良事件。
20 例患者（9 例 CD、10 例 UC、1 例 IBD-U；55%为女性；中位年龄 15 岁，90%≥2 种生物制剂）接受 UPA 治疗≥12 周（中位 51[43-63]周）。UPA 单药治疗占 55%，联合 ustekinumab 和 vedolizumab 治疗分别占 35%和 10%。12 周时达到 SF-CR 的患者占 75%（15/20），CRP 正常化的患者占 80%（16/20）。约 3/4（14/19）的患者在 6 个月时达到 SF-CR。2 例患者（10%）发生不良事件：需要住院治疗的巨细胞病毒结肠炎和无需治疗的血脂异常。在接受超声监测的 75%患者中，分别有 77%和 60%达到了应答和缓解。
在等待儿科注册试验期间，我们的数据表明 UPA 在治疗难治性青少年 IBD 方面有效，诱导和维持 SF-CR 的效果较好，安全性可接受。
