乌达帕替尼治疗肛周瘘性克罗恩病的疗效和安全性:对 3 项 3 期试验的事后分析。

IF 11.6 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Clinical Gastroenterology and Hepatology Pub Date : 2024-09-24 DOI:10.1016/j.cgh.2024.08.032
Jean-Frédéric Colombel, Ana P Lacerda, Peter M Irving, Remo Panaccione, Walter Reinisch, Florian Rieder, Adam Steinlauf, David Schwartz, Tian Feng, Elena Dubcenco, Samuel I Anyanwu, F Stephen Laroux, Colla Cunneen, Nick Powell
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引用次数: 0

摘要

背景与目的:口服Janus激酶抑制剂upadacitinib治疗中重度克罗恩病的疗效已在3期诱导(U-EXCEL、U-EXCEED)和维持(U-ENDURE)试验中得到证实;这项事后分析评估了这些研究中瘘管化疾病患者的upadacitinib疗效:患者被随机(2:1)分配至每日一次的达达替尼 45 毫克(UPA45)或安慰剂,为期 12 周。UPA45临床应答者被重新随机分组(1:1:1)至达帕替尼15毫克(UPA15)、30毫克(UPA30)或安慰剂,为期52周。对瘘管(任何瘘管和肛周瘘管)患者的引流恢复情况、外部开口闭合情况、临床缓解情况、内窥镜反应和安全性进行了评估:U-EXCEL和U-EXCEED的1021名患者中,143人(14.0%)在基线时有瘘管(66人引流通畅);其中大多数(128人)有肛周瘘管(56人引流通畅)。在诱导治疗(安慰剂,5.6%,n/N = 1/18;UPA45,44.7%,n/N = 17/38;P = .003)和维持治疗(安慰剂,0%,n/N = 0/11;UPA15,28.6%,n/N = 4/14;P = .结论:结论:与安慰剂相比,接受高达替尼治疗的瘘管病(主要是肛周瘘管病)患者的引流通畅率、外部开口闭合率、临床缓解率和内镜反应率都更高:U-excel (NCT03345849)、U-exceed (NCT03345836)、U-endure (NCT03345823)。
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Efficacy and Safety of Upadacitinib for Perianal Fistulizing Crohn's Disease: A Post Hoc Analysis of 3 Phase 3 Trials.

Background & aims: Efficacy of upadacitinib, an oral Janus kinase inhibitor, for moderate-to-severe Crohn's disease was demonstrated in phase 3 induction (U-EXCEL, U-EXCEED) and maintenance (U-ENDURE) trials; this post hoc analysis evaluated upadacitinib outcomes in patients with fistulizing disease in these studies.

Methods: Patients were randomized (2:1) to once daily upadacitinib 45 mg or placebo for 12 weeks. Upadacitinib 45 mg clinical responders were rerandomized (1:1:1) to upadacitinib 15 mg, upadacitinib 30 mg, or placebo for 52 weeks. In patients with fistulas (any and perianal), resolution of drainage, closure of external openings, clinical remission, endoscopic response, and safety were assessed.

Results: Of 1021 patients in U-EXCEL and U-EXCEED, 143 (14.0%) had any fistulas at baseline (66 draining); of these, most (n = 128) had perianal fistulas (56 draining). Greater proportions of patients receiving upadacitinib vs placebo achieved resolution of drainage of perianal fistulas at the end of induction (placebo: 5.6%, n/n = 1/18; upadacitinib 45 mg: 44.7%, n/n = 17/38; P = .003) and maintenance (placebo: 0%, n/n = 0/11; upadacitinib 15 mg: 28.6%, n/n = 4/14; P = .105; upadacitinib 30 mg: 23.1% n/n = 3/13; P = .223) and closure of perianal fistula external openings (for induction, placebo: 4.8%, n/n = 2/42; upadacitinib 45 mg: 22.1%, n/n = 19/86; P = .013; for maintenance, placebo: 0%, n/n = 0/30; upadacitinib 15 mg: 18.8%, n/n = 6/32; P = .024; upadacitinib 30 mg: 16.0%, n/n = 4/25; P = .037).

Conclusion: Patients with fistulizing disease (primarily perianal) treated with upadacitinib achieved higher rates of resolution of drainage, closure of external openings, clinical remission, and endoscopic response vs placebo.

Clinicaltrials: gov, Numbers: NCT03345849 (U-EXCEL), NCT03345836 (U-EXCEED), NCT03345823 (U-ENDURE).

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来源期刊
CiteScore
16.90
自引率
4.80%
发文量
903
审稿时长
22 days
期刊介绍: Clinical Gastroenterology and Hepatology (CGH) is dedicated to offering readers a comprehensive exploration of themes in clinical gastroenterology and hepatology. Encompassing diagnostic, endoscopic, interventional, and therapeutic advances, the journal covers areas such as cancer, inflammatory diseases, functional gastrointestinal disorders, nutrition, absorption, and secretion. As a peer-reviewed publication, CGH features original articles and scholarly reviews, ensuring immediate relevance to the practice of gastroenterology and hepatology. Beyond peer-reviewed content, the journal includes invited key reviews and articles on endoscopy/practice-based technology, health-care policy, and practice management. Multimedia elements, including images, video abstracts, and podcasts, enhance the reader's experience. CGH remains actively engaged with its audience through updates and commentary shared via platforms such as Facebook and Twitter.
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