Single-center Experience With Upadacitinib for Adolescents With Refractory Inflammatory Bowel Disease.
Single-center Experience With Upadacitinib for Adolescents With Refractory Inflammatory Bowel Disease.
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Upadacitinib 用于治疗难治性炎症性肠病青少年的单中心经验。
DOI：
10.1093/ibd/izad300
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发表时间：
2023
影响因子：
4.9
通讯作者：
Dubinsky,MarlaC
中科院分区：
文献类型：
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作者：
Spencer,ElizabethA;Bergstein,Suzannah;Dolinger,Michael;Pittman,Nanci;Kellar,Amelia;Dunkin,David;Dubinsky,MarlaC
Upadacitinib(UPA)是一种新型的选择性JAK抑制剂，被批准用于成人溃疡性结肠炎(UC)和克罗恩病(CD)阳性的3期试验。由于儿科审批的延迟，儿科非标签使用是常见的；需要关于uPA的真实数据来了解儿童IBD的安全性和有效性。方法这是一项关于患有炎症性肠病的青少年(12-17岁)服用uPA的单中心回顾性病例系列研究。主要结果是诱导后无激素临床缓解(SF-CR)，定义为儿童UC活动指数或儿童CD活动指数≤10。次要结果包括诱导后临床反应(PUCAI/PCDAI下降12.5%)，诱导后C反应蛋白正常化，6个月SF-CR，以及肠道超声反应和缓解。结果20例患者(CD 9例，UC 10例，IBD-U 1例；女性55%；中位年龄15岁，90%的≥2生物制剂)接受≥治疗12周(中位数51[43~63]周)。55%的患者单用厄帕西替尼，35%的患者与乌司他单抗、维多利单抗联合应用。12周时CRP复常率分别为75%(15/20)和80%(16/20)。约3/4(14/19)患者在6个月时达到SF-CR。不良事件2例(10%)：巨细胞病毒性结肠炎需住院治疗，高脂血症不需治疗。在超声监测的75%中，有效率和缓解率分别为77%和60%。结论在等待儿科注册试验期间，我们的数据表明，uPA在高度难治性IBD的青少年患者中诱导和维持SF-CR是有效的，且安全性可接受。
BackgroundUpadacitinib (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.MethodsThis 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.ResultsTwenty 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.ConclusionWhile 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.