Pub Date : 2024-12-11DOI: 10.1016/s2468-1253(24)00392-3
Rob Brierley
Section snippets
Semaglutide for MASH
Semaglutide 2·4 mg once a week demonstrated significantly greater improvements in histology and fibrosis than did placebo in participants with metabolic dysfunction-associated steatohepatitis (MASH) with F2–F3 fibrosis, according to data from the phase 3 ESSENCE trial. Although the trial is ongoing, Phil Newsome (London, UK) presented data from the prespecified interim analysis at week 72 of the first 800 participants, of whom 534 had been randomly assigned to receive semaglutide and 266 had
Optimising steroid use in severe alcohol-associated hepatitis
Tapering the dose of corticosteroids is safer and just as efficacious as conventional fixed-dose corticosteroids for severe alcohol-associated hepatitis, according to results from the STASH trial, presented by Anand Kulkarni (Hyderabad, India). Patients with severe alcohol-associated hepatitis were randomly assigned to receive either a fixed-dose or tapering regimen. Patients in each group initially received 40 mg prednisolone a day for 7 days. Patients in the fixed dose group with a Lille
CM-101 in primary sclerosing cholangitis
CM-101, an anti-CCL24 monoclonal antibody, exhibited promising activity in patients with primary sclerosing cholangitis and had a safety profile similar to placebo, according to data from the phase 2 SPRING study. In this placebo-controlled trial, presented by Christopher Bowlus (Davis, CA, USA), patients with primary sclerosing cholangitis were randomly assigned to receive either CM-101 at 10 mg/kg (n=25), CM-101 at 20 mg/kg (n=31), or placebo (n=21) every 3 weeks for 15 weeks.
VK2809 for steatotic liver disease
The phase 2b VOYAGE trial examined the use of VK2809, a small molecule thyroid hormone receptor beta agonist prodrug that is selectively cleaved in hepatic tissue by cytochrome P450 3A4 to release a pharmacologically active metabolite, in individuals with biopsy-confirmed non-alcoholic fatty liver disease and fibrosis. Participants were randomly assigned to receive placebo or VK2809 at 1 mg/day, 2·5 mg/day, 5 mg/day, or 10 mg/day. Percentage change in MRI-PDFF at 3 months was –56·7% in the
{"title":"The Liver Meeting 2024","authors":"Rob Brierley","doi":"10.1016/s2468-1253(24)00392-3","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00392-3","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Semaglutide for MASH</h2>Semaglutide 2·4 mg once a week demonstrated significantly greater improvements in histology and fibrosis than did placebo in participants with metabolic dysfunction-associated steatohepatitis (MASH) with F2–F3 fibrosis, according to data from the phase 3 ESSENCE trial. Although the trial is ongoing, Phil Newsome (London, UK) presented data from the prespecified interim analysis at week 72 of the first 800 participants, of whom 534 had been randomly assigned to receive semaglutide and 266 had</section></section><section><section><h2>Optimising steroid use in severe alcohol-associated hepatitis</h2>Tapering the dose of corticosteroids is safer and just as efficacious as conventional fixed-dose corticosteroids for severe alcohol-associated hepatitis, according to results from the STASH trial, presented by Anand Kulkarni (Hyderabad, India). Patients with severe alcohol-associated hepatitis were randomly assigned to receive either a fixed-dose or tapering regimen. Patients in each group initially received 40 mg prednisolone a day for 7 days. Patients in the fixed dose group with a Lille</section></section><section><section><h2>CM-101 in primary sclerosing cholangitis</h2>CM-101, an anti-CCL24 monoclonal antibody, exhibited promising activity in patients with primary sclerosing cholangitis and had a safety profile similar to placebo, according to data from the phase 2 SPRING study. In this placebo-controlled trial, presented by Christopher Bowlus (Davis, CA, USA), patients with primary sclerosing cholangitis were randomly assigned to receive either CM-101 at 10 mg/kg (n=25), CM-101 at 20 mg/kg (n=31), or placebo (n=21) every 3 weeks for 15 weeks.</section></section><section><section><h2>VK2809 for steatotic liver disease</h2>The phase 2b VOYAGE trial examined the use of VK2809, a small molecule thyroid hormone receptor beta agonist prodrug that is selectively cleaved in hepatic tissue by cytochrome P450 3A4 to release a pharmacologically active metabolite, in individuals with biopsy-confirmed non-alcoholic fatty liver disease and fibrosis. Participants were randomly assigned to receive placebo or VK2809 at 1 mg/day, 2·5 mg/day, 5 mg/day, or 10 mg/day. Percentage change in MRI-PDFF at 3 months was –56·7% in the</section></section>","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"29 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-11DOI: 10.1016/s2468-1253(24)00401-1
Janssen HLA, Lim Y-S, Lampertico P, et al. Switching to tenofovir alafenamide in patients with virologically suppressed chronic hepatitis B and renal or hepatic impairment: final week 96 results from an open-label, multicentre, phase 2 study. Lancet Gastroenterol Hepatol 2024; 9: 718–33—In this Article, the label for previous other oral antiviral in figure 3B should have read 0·04; the label for previous tenofovir disproxil fumarate in figure 4C should have read 1·09%; and the label for tenofovir alafenamide in figure 4C should have read 0·28%. These corrections have been made to the online version as of Dec 11, 2024.
{"title":"Correction to Lancet Gastroenterol Hepatol 2024; 9: 718–33","authors":"","doi":"10.1016/s2468-1253(24)00401-1","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00401-1","url":null,"abstract":"<em>Janssen HLA, Lim Y-S, Lampertico P, et al. Switching to tenofovir alafenamide in patients with virologically suppressed chronic hepatitis B and renal or hepatic impairment: final week 96 results from an open-label, multicentre, phase 2 study.</em> Lancet Gastroenterol Hepatol <em>2024;</em> 9: <em>718–33</em>—In this Article, the label for previous other oral antiviral in figure 3B should have read 0·04; the label for previous tenofovir disproxil fumarate in figure 4C should have read 1·09%; and the label for tenofovir alafenamide in figure 4C should have read 0·28%. These corrections have been made to the online version as of Dec 11, 2024.","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"538 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-09DOI: 10.1016/s2468-1253(24)00351-0
Andreas A Schnitzbauer
No Abstract
没有抽象的
{"title":"Hypovolaemic phlebotomy to reduce the need for perioperative transfusion: a price worth paying?","authors":"Andreas A Schnitzbauer","doi":"10.1016/s2468-1253(24)00351-0","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00351-0","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"148 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-09DOI: 10.1016/s2468-1253(24)00307-8
Guillaume Martel, François Martin Carrier, Christopher Wherrett, Tori Lenet, Katlin Mallette, Karine Brousseau, Leah Monette, Aklile Workneh, Monique Ruel, Elham Sabri, Heather Maddison, Melanie Tokessy, Patrick B Y Wong, Franck Vandenbroucke-Menu, Luc Massicotte, Michaël Chassé, Yves Collin, Michel-Antoine Perrault, Élodie Hamel-Perreault, Jeieung Park, Dean A Fergusson
<h3>Background</h3>Blood loss and subsequent red blood cell transfusions are common in liver surgery. Hypovolaemic phlebotomy is associated with decreased red blood cell transfusion in observational studies. This trial aimed to investigate whether hypovolaemic phlebotomy is superior to usual care in reducing red blood cell transfusions in patients undergoing liver resection.<h3>Methods</h3>PRICE-2 was a multicentre, single-blind, superiority randomised controlled trial. Patients at a higher risk of blood loss undergoing liver resection for any indication at four Canadian academic tertiary-care hospitals were randomised to receive hypovolaemic phlebotomy or usual care. Hypovolaemic phlebotomy consisted of the removal of 7–10 mL/kg of whole blood, without volume replacement, before liver transection. Patients were randomised centrally using permuted blocks of randomly variable length, stratified by centre. The randomisation sequence was computer-generated by an independent statistician. Surgeons, patients, and outcome assessors were masked to treatment allocation. The primary outcome was perioperative red blood cell transfusion to 30 days post-randomisation, analysed in all randomly assigned patients who underwent liver resection. PRICE-2 trial was registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span> (<span><span>NCT03651154</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>) and is completed.<h3>Findings</h3>Between Oct 1, 2018, and Jan 13, 2023, 486 individuals were randomly assigned to receive hypovolaemic phlebotomy (n=245) or usual care (n=241). 22 individuals in the hypovolaemic phlebotomy group and 18 in the usual care group did not undergo liver resection and were thus excluded from the primary analysis population. 223 patients were included in the hypovolaemic phlebotomy group (mean age 61·4 years [SD 13·0]; 137 [61%] men) and 223 in the control group (62·1 years [12·1]; 114 [51%]). 17 (8%) of 223 patients allocated to hypovolaemic phlebotomy and 36 (16%) of 223 patients allocated to usual care had a perioperative red blood cell transfusion by 30 days (difference –8·8 percentage points [95% CI –14·8 to –2·8]; adjusted risk ratio [aRR] 0·47 [95% CI 0·27 to 0·82]). Severe complications to 30 days occurred in 37 (17%) patients allocated to hypovolaemic phlebotomy and 36 (16%) allocated to usual care (aRR 1·06 [95% CI 0·70–1·61]). Overall complications to 30 days occurred in 135 (61%) of 223 patients allocated to hypovolaemic phlebotomy and 116 (52%) of 223 patients allocated to usual care (1·08 [0·92–1·25]). There was no postoperative mortality to 90 days.<h3>Interpretation</h3>In p
背景：在肝脏手术中，失血和随后的红细胞输注是很常见的。在观察性研究中，低血容量放血术与红细胞输注减少有关。本试验旨在探讨低容性静脉切开术在减少肝切除术患者红细胞输注方面是否优于常规护理。方法price -2是一项多中心、单盲、优势随机对照试验。在加拿大四家学术三级医院中，因任何适应症而行肝切除术的失血风险较高的患者被随机分组，接受低血容量放血或常规治疗。低血容量静脉切开术包括在肝横断前不进行容量置换，抽取7-10 mL/kg全血。采用随机可变长度的排列块对患者进行中心随机分组，按中心分层。随机序列是由一位独立的统计学家用电脑生成的。外科医生、患者和结果评估者对治疗分配不知情。主要结局是随机分组后30天的围手术期红细胞输血，分析所有随机分配的接受肝切除术的患者。PRICE-2试验已在ClinicalTrials.gov注册（NCT03651154），并已完成。在2018年10月1日至2023年1月13日期间，486名患者被随机分配接受低血容量放血（n=245）或常规治疗（n=241）。低血容量放血组的22例患者和常规护理组的18例患者未行肝切除术，因此被排除在初步分析人群之外。低血容量放血组223例，平均年龄64.1岁[SD 13.0]；男性137例（61%），对照组223例（62.1岁，12.1岁）；114[51%])。223名低容性放血患者中有17名（8%）和223名常规护理患者中有36名（16%）在30天内进行了围手术期红细胞输注(差异为- 8.8个百分点[95% CI - 14.8至-2·8]；校正风险比[aRR] 0.47 [95% CI 0.27 ~ 0.82])。低血容量放血组37例（17%）患者出现严重并发症，常规护理组36例（16%）患者出现严重并发症（aRR 1.06 [95% CI 0.70 - 1.61]）。223例低血容量放血患者中有135例（61%）出现30天总并发症，223例常规护理患者中有116例（52%）出现并发症（1.08[0.92 - 0.25]）。术后90天无死亡。解释：在肝切除术患者中，低血容量静脉切开术减少了围手术期红细胞输注，改善了手术条件，与常规治疗相比，并发症发生率无统计学意义的增加。低血容量静脉切开术应被认为是肝切除术中出血风险较高的患者的常规应用。加拿大卫生研究所资助（PJT-156108）。
{"title":"Hypovolaemic phlebotomy in patients undergoing hepatic resection at higher risk of blood loss (PRICE-2): a randomised controlled trial","authors":"Guillaume Martel, François Martin Carrier, Christopher Wherrett, Tori Lenet, Katlin Mallette, Karine Brousseau, Leah Monette, Aklile Workneh, Monique Ruel, Elham Sabri, Heather Maddison, Melanie Tokessy, Patrick B Y Wong, Franck Vandenbroucke-Menu, Luc Massicotte, Michaël Chassé, Yves Collin, Michel-Antoine Perrault, Élodie Hamel-Perreault, Jeieung Park, Dean A Fergusson","doi":"10.1016/s2468-1253(24)00307-8","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00307-8","url":null,"abstract":"<h3>Background</h3>Blood loss and subsequent red blood cell transfusions are common in liver surgery. Hypovolaemic phlebotomy is associated with decreased red blood cell transfusion in observational studies. This trial aimed to investigate whether hypovolaemic phlebotomy is superior to usual care in reducing red blood cell transfusions in patients undergoing liver resection.<h3>Methods</h3>PRICE-2 was a multicentre, single-blind, superiority randomised controlled trial. Patients at a higher risk of blood loss undergoing liver resection for any indication at four Canadian academic tertiary-care hospitals were randomised to receive hypovolaemic phlebotomy or usual care. Hypovolaemic phlebotomy consisted of the removal of 7–10 mL/kg of whole blood, without volume replacement, before liver transection. Patients were randomised centrally using permuted blocks of randomly variable length, stratified by centre. The randomisation sequence was computer-generated by an independent statistician. Surgeons, patients, and outcome assessors were masked to treatment allocation. The primary outcome was perioperative red blood cell transfusion to 30 days post-randomisation, analysed in all randomly assigned patients who underwent liver resection. PRICE-2 trial was registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> (<span><span>NCT03651154</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>) and is completed.<h3>Findings</h3>Between Oct 1, 2018, and Jan 13, 2023, 486 individuals were randomly assigned to receive hypovolaemic phlebotomy (n=245) or usual care (n=241). 22 individuals in the hypovolaemic phlebotomy group and 18 in the usual care group did not undergo liver resection and were thus excluded from the primary analysis population. 223 patients were included in the hypovolaemic phlebotomy group (mean age 61·4 years [SD 13·0]; 137 [61%] men) and 223 in the control group (62·1 years [12·1]; 114 [51%]). 17 (8%) of 223 patients allocated to hypovolaemic phlebotomy and 36 (16%) of 223 patients allocated to usual care had a perioperative red blood cell transfusion by 30 days (difference –8·8 percentage points [95% CI –14·8 to –2·8]; adjusted risk ratio [aRR] 0·47 [95% CI 0·27 to 0·82]). Severe complications to 30 days occurred in 37 (17%) patients allocated to hypovolaemic phlebotomy and 36 (16%) allocated to usual care (aRR 1·06 [95% CI 0·70–1·61]). Overall complications to 30 days occurred in 135 (61%) of 223 patients allocated to hypovolaemic phlebotomy and 116 (52%) of 223 patients allocated to usual care (1·08 [0·92–1·25]). There was no postoperative mortality to 90 days.<h3>Interpretation</h3>In p","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"234 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-05DOI: 10.1016/s2468-1253(24)00311-x
Serena Porcari, Benjamin H Mullish, Francesco Asnicar, Siew C Ng, Liping Zhao, Richard Hansen, Paul W O'Toole, Jeroen Raes, Georgina Hold, Lorenza Putignani, Christian Lodberg Hvas, Georg Zeller, Omry Koren, Hein Tun, Mireia Valles-Colomer, Maria Carmen Collado, Monika Fischer, Jessica Allegretti, Tariq Iqbal, Benoit Chassaing, Gianluca Ianiro
There is growing interest in the potential exploitation of the gut microbiome as a diagnostic tool in medicine, but evidence supporting its clinical usefulness is scarce. An increasing number of commercial providers offer direct-to-consumer microbiome diagnostic tests without any consensus on their regulation or any proven value in clinical practice, which could result in considerable waste of individual and health-care resources and potential drawbacks in the clinical management of patients. We convened an international multidisciplinary expert panel to standardise best practices of microbiome testing for clinical implementation, including recommendations on general principles and minimum requirements for their provision, indications, pre-testing protocols, method of analyses, reporting of results, and potential clinical value. We also evaluated current knowledge gaps and future directions in this field. We aimed to establish a framework to regulate the provision of microbiome testing and minimise the use of inappropriate tests and pave the way for the evidence-based development and use of human microbiome diagnostics in clinical medicine.
{"title":"International consensus statement on microbiome testing in clinical practice","authors":"Serena Porcari, Benjamin H Mullish, Francesco Asnicar, Siew C Ng, Liping Zhao, Richard Hansen, Paul W O'Toole, Jeroen Raes, Georgina Hold, Lorenza Putignani, Christian Lodberg Hvas, Georg Zeller, Omry Koren, Hein Tun, Mireia Valles-Colomer, Maria Carmen Collado, Monika Fischer, Jessica Allegretti, Tariq Iqbal, Benoit Chassaing, Gianluca Ianiro","doi":"10.1016/s2468-1253(24)00311-x","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00311-x","url":null,"abstract":"There is growing interest in the potential exploitation of the gut microbiome as a diagnostic tool in medicine, but evidence supporting its clinical usefulness is scarce. An increasing number of commercial providers offer direct-to-consumer microbiome diagnostic tests without any consensus on their regulation or any proven value in clinical practice, which could result in considerable waste of individual and health-care resources and potential drawbacks in the clinical management of patients. We convened an international multidisciplinary expert panel to standardise best practices of microbiome testing for clinical implementation, including recommendations on general principles and minimum requirements for their provision, indications, pre-testing protocols, method of analyses, reporting of results, and potential clinical value. We also evaluated current knowledge gaps and future directions in this field. We aimed to establish a framework to regulate the provision of microbiome testing and minimise the use of inappropriate tests and pave the way for the evidence-based development and use of human microbiome diagnostics in clinical medicine.","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"3 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-02DOI: 10.1016/s2468-1253(24)00304-2
Mark Andrew Ainsworth
No Abstract
没有抽象的
{"title":"Does filgotinib work for Crohn's disease?","authors":"Mark Andrew Ainsworth","doi":"10.1016/s2468-1253(24)00304-2","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00304-2","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"4 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142760073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-02DOI: 10.1016/s2468-1253(24)00272-3
Séverine Vermeire, Stefan Schreiber, David T Rubin, Geert D'Haens, Walter Reinisch, Mamoru Watanabe, Rajiv Mehta, Xavier Roblin, Ian Beales, Piotr Gietka, Toshifumi Hibi, Ihor Hospodarskyy, Timothy Ritter, Mark C Genovese, Paul Kwon, Eva Santermans, Franck-Olivier Le Brun, Rahul Barron, Tomasz Masior, Silvio Danese
<h3>Background</h3>There is a need for efficacious therapies for patients with Crohn's disease that are better tolerated and more durable than available treatments. We aimed to evaluate the efficacy and safety of filgotinib, an oral Janus kinase 1 preferential inhibitor, for treating Crohn's disease.<h3>Methods</h3>This phase 3, double-blind, randomised, placebo-controlled trial was conducted in 371 centres in 39 countries. Eligible patients were aged 18–75 years with moderately to severely active Crohn's disease for at least 3 months before enrolment. Patients were enrolled into one of two induction studies on the basis of their experience with biological agents (induction study A included biologic-naive and later biologic-experienced patients and induction study B included biologic-experienced patients). In both induction studies, patients were randomly assigned (1:1:1), using an interactive web response system, to receive oral filgotinib 200 mg, filgotinib 100 mg, or placebo once daily for 11 weeks. Patients who received filgotinib and had two-item patient-reported outcome (PRO2) clinical remission or an endoscopic response at week 10 were re-randomised (2:1) to receive their induction dose or placebo orally, once daily to the end of week 58 in the maintenance study. Co-primary endpoints were PRO2 clinical remission and an endoscopic response at week 10 (induction studies) and week 58 (maintenance study). PRO2 clinical remission was defined as an abdominal pain subscore of not more than 1 and a liquid or very soft stool frequency subscore of not more than 3 (from eDiary data) and endoscopic response was defined as a reduction of at least 50% in Simple Endoscopic Score for Crohn's disease from induction baseline (from central reading of endoscopy). For the induction studies, efficacy was assessed in all randomly assigned patients who received at least one dose of study drug. For the maintenance study, efficacy was assessed in all patients from either filgotinib treatment group in the induction studies who reached PRO2 clinical remission or an endoscopic response at week 10, and who were re-randomised and received at least one dose of study drug in the maintenance study. Patients who received placebo throughout the induction and maintenance studies were not included in the full analysis set for the maintenance study. Safety was assessed in all patients who received at least one dose of study drug. This trial is complete and is registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>, <span><span>NCT02914561</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>.<h3>Findings</h3>Between Oct 31,
研究背景：对于克罗恩病患者，需要比现有治疗方法更耐受性和更持久的有效治疗方法。我们的目的是评估非戈替尼（一种口服Janus激酶1优先抑制剂）治疗克罗恩病的有效性和安全性。该三期、双盲、随机、安慰剂对照试验在39个国家的371个中心进行。符合条件的患者年龄为18-75岁，入组前患有中度至重度活动期克罗恩病至少3个月。根据患者使用生物制剂的经验，将患者纳入两项诱导研究中的一项（诱导研究A包括未使用生物制剂和后来有生物制剂经验的患者，诱导研究B包括有生物制剂经验的患者）。在这两项诱导研究中，患者被随机分配（1:1:1），使用交互式网络反应系统，接受口服filgotinib 200mg， filgotinib 100mg或安慰剂，每天一次，持续11周。在维持研究中，接受非戈替尼治疗并在第10周有两项患者报告结果（PRO2）临床缓解或内窥镜反应的患者被重新随机分配（2:1），接受诱导剂量或口服安慰剂，每天一次，直到第58周结束。共同主要终点是第10周（诱导研究）和第58周（维持研究）的PRO2临床缓解和内窥镜反应。PRO2临床缓解被定义为腹痛亚分不超过1分，液体或非常软的大便频率亚分不超过3分（来自每日数据），内镜下反应被定义为克罗恩病简单内镜评分从诱导基线（来自内镜中心读数）减少至少50%。在诱导研究中，对所有随机分配的接受至少一剂研究药物的患者进行疗效评估。在维持研究中，对诱导研究中非戈替尼治疗组中所有在第10周达到PRO2临床缓解或内窥镜反应的患者进行疗效评估，这些患者在维持研究中被重新随机分配并接受至少一剂研究药物。在整个诱导和维持研究中接受安慰剂的患者未被纳入维持研究的完整分析集。对所有接受至少一剂研究药物的患者进行安全性评估。该试验已经完成并在ClinicalTrials.gov注册，编号NCT02914561。在2016年10月31日至2022年11月11日期间，筛选了2634例患者，其中1372例入组（诱导研究A: n=707，诱导研究B: n=665，维持研究：n=481）。诱导研究A中有346名（49%）女性和358名（51%）男性，诱导研究B中有356名（54%）女性和303名（46%）男性，维持研究中有242名（51%）女性和236名（49%）男性。在诱导研究B中，非戈替尼200mg组在第10周获得PRO2临床缓解的患者明显多于安慰剂组(29.7% vs 17.9%，差异11.9%；95% CI 3.7 ~ 20.2, p= 0.0039)，但诱导研究A没有(32.9% vs 25.7%, 6.9%；-1·4 ~ 15.2,p=0·0963)；内镜下反应无显著差异(诱导研究A: 23.9% vs 18.1%，差异5.5%；95% CI -2·0 ~ 12.9,p= 0.1365；诱导研究B: 11.9% vs 11.4%, 0.1%；- 6.5 ~ 6.6, p= 0.9797)。在第58周，接受非戈替尼200mg的患者比接受安慰剂的患者有更大的比例报告这两个共同主要终点(PRO2临床缓解：43.8% vs 26.4%，差16.8%；95% CI 2·0 ~ 31.6,p=0·0382；内镜下反应：30.4% vs 9.4%，差20.6%；95% CI为8.2 ~ 33.1,p= 0.0038)。非戈替尼100 mg在任何研究中均未达到共同主要终点。在诱导研究中，最常见的治疗不良事件(teae；≥5%的患者在任何组)腹痛；关节痛;克罗恩病的恶化、突然发作或恶化；头痛;鼻咽炎;恶心;和发热。在维持研究中，最常报告的teae（非戈替尼或相关安慰剂组中≥5%的患者）是诱导研究（头痛除外）和腹胀、上腹痛、贫血和胀气中报告的teae。 严重流泪是在49个病人在归纳研究报告(18[8%])的222名患者filgotinib 200毫克组,16 (7%)filgotinib 100毫克组的245名患者,15(6%),安慰剂组)237例,81例患者在归纳研究B (19 [9%] filgotinib 200毫克组的202名患者,36 [16%]filgotinib 100毫克组的228名患者和26(11%)的229例安慰剂组),49例患者在维持研究中（118例非戈替尼200 mg -非戈替尼200 mg组中有13例[11%]，56例非戈替尼200 mg -安慰剂组中有5例[9%]，104例非戈替尼100 mg -非戈替尼100 mg组中有14例[13%]，55例非戈替尼100 mg -安慰剂组中有3例[5%]，145例安慰剂-安慰剂组中有14例[10%]）。在诱导和维持研究期间无死亡报告。解释：非哥替尼200mg在第10周没有达到临床缓解和内窥镜反应的共同主要终点，但在第58周确实达到了共同主要终点。非哥替尼治疗耐受性良好，没有新的安全性信号报道。
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