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
{"title":"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。","authors":"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","doi":"10.1016/j.cgh.2024.08.032","DOIUrl":null,"url":null,"abstract":"<p><strong>Background & aims: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p><p><strong>Clinicaltrials: </strong>gov, Numbers: NCT03345849 (U-EXCEL), NCT03345836 (U-EXCEED), NCT03345823 (U-ENDURE).</p>","PeriodicalId":10347,"journal":{"name":"Clinical Gastroenterology and Hepatology","volume":" ","pages":""},"PeriodicalIF":11.6000,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Efficacy and Safety of Upadacitinib for Perianal Fistulizing Crohn's Disease: A Post Hoc Analysis of 3 Phase 3 Trials.\",\"authors\":\"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\",\"doi\":\"10.1016/j.cgh.2024.08.032\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background & aims: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p><p><strong>Clinicaltrials: </strong>gov, Numbers: NCT03345849 (U-EXCEL), NCT03345836 (U-EXCEED), NCT03345823 (U-ENDURE).</p>\",\"PeriodicalId\":10347,\"journal\":{\"name\":\"Clinical Gastroenterology and Hepatology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":11.6000,\"publicationDate\":\"2024-09-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Gastroenterology and Hepatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.cgh.2024.08.032\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Gastroenterology and Hepatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.cgh.2024.08.032","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
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.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
