首页 > 最新文献

Lancet Gastroenterology & Hepatology最新文献

英文 中文
Denifanstat for the treatment of metabolic dysfunction-associated steatohepatitis 地尼芬司他治疗代谢功能障碍相关脂肪性肝炎
IF 35.7 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-01-10 DOI: 10.1016/s2468-1253(24)00388-1
Xincheng Li, Ibrahim Ayada, Pengfei Li, Qiuwei Pan
No Abstract
没有抽象的
{"title":"Denifanstat for the treatment of metabolic dysfunction-associated steatohepatitis","authors":"Xincheng Li, Ibrahim Ayada, Pengfei Li, Qiuwei Pan","doi":"10.1016/s2468-1253(24)00388-1","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00388-1","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"118 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961898","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}
引用次数: 0
Bridging gaps in surgical care for neuroendocrine tumours: CUTNETs begins 弥合神经内分泌肿瘤外科护理的差距:CUTNETs开始
IF 35.7 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-01-10 DOI: 10.1016/s2468-1253(24)00406-0
Julie Hallet, Massimo Falconi, Stefano Partelli
No Abstract
没有抽象的
{"title":"Bridging gaps in surgical care for neuroendocrine tumours: CUTNETs begins","authors":"Julie Hallet, Massimo Falconi, Stefano Partelli","doi":"10.1016/s2468-1253(24)00406-0","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00406-0","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"7 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961837","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}
引用次数: 0
Denifanstat for the treatment of metabolic dysfunction-associated steatohepatitis 地尼芬司他治疗代谢功能障碍相关脂肪性肝炎
IF 35.7 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-01-10 DOI: 10.1016/s2468-1253(24)00404-7
Ziwei Gao, Wei Ye, Jingru Song
No Abstract
没有抽象的
{"title":"Denifanstat for the treatment of metabolic dysfunction-associated steatohepatitis","authors":"Ziwei Gao, Wei Ye, Jingru Song","doi":"10.1016/s2468-1253(24)00404-7","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00404-7","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"26 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961887","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}
引用次数: 0
Denifanstat for the treatment of metabolic dysfunction-associated steatohepatitis – Authors' reply 地尼芬司他治疗代谢功能障碍相关脂肪性肝炎——作者的答复
IF 35.7 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-01-10 DOI: 10.1016/s2468-1253(24)00433-3
George Kemble, Katharine Grimmer, Eduardo Bruno Martins, William McCulloch, Marie O’Farrell, Wen-Wei Tsai, Rohit Loomba
No Abstract
没有抽象的
{"title":"Denifanstat for the treatment of metabolic dysfunction-associated steatohepatitis – Authors' reply","authors":"George Kemble, Katharine Grimmer, Eduardo Bruno Martins, William McCulloch, Marie O’Farrell, Wen-Wei Tsai, Rohit Loomba","doi":"10.1016/s2468-1253(24)00433-3","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00433-3","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"39 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961899","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}
引用次数: 0
Research in Brief 研究简介
IF 35.7 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-01-10 DOI: 10.1016/s2468-1253(24)00440-0
Holly Baker
<h2>Section snippets</h2><section><section><h2>Guselkumab for moderately to severely active ulcerative colitis</h2>Guselkumab is a safe and efficacious treatment option for patients with moderately to severely active ulcerative colitis, according to the <span><span>phase 3 QUASAR induction and maintenance studies</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>. David T Rubin and colleagues randomly assigned patients with inadequate response or intolerance to conventional or advanced ulcerative colitis therapy to receive guselkumab 200 mg intravenously (n=421) or placebo (n=280) at weeks 0, 4, and 8 (induction study). At 12 weeks, 95 (23%) of 421 patients in the</section></section><section><section><h2>Nivolumab plus ipilimumab for MSI-H colorectal cancer</h2>Nivolumab plus ipilimumab increases survival in patients with microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) metastatic colorectal cancer, according to the phase 3 <span><span>CheckMate 8HW trial</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>. Thierry Andre and colleagues randomly assigned patients with unresectable or metastatic colorectal cancer and MSI-H or dMMR status according to local testing to receive either nivolumab plus ipilimumab, nivolumab alone, or chemotherapy with or without targeted therapies. In this</section></section><section><section><h2><span><span>Impact of coeliac disease on gut function and microbiome</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></h2>Coeliac disease has an impact on gut function and microbiome composition that is not reversed by a gluten-free diet, according to new research. Carolyn Costigan and colleagues used MRI and stool sample analysis to examine gut function and microbiome composition of 36 patients with newly diagnosed coeliac disease and an equal number of healthy volunteers. At baseline, patients with coeliac disease had significantly higher small bowel water content and delayed gut transit times compared with</section></section><section><section><h2>Combination therapy for acute severe ulcerative colitis</h2>Combination therapy with infliximab plus azathioprine shows promise in patients with acute severe ulcerative colitis responsive to intravenous steroids, according to the <span><span>phase 4 ACTIVE trial</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>. Aurelien Am
根据类星体的3期诱导和维持研究,guselkumab对于中度至重度活动性溃疡性结肠炎患者是一种安全有效的治疗选择。David T Rubin及其同事随机分配对常规或晚期溃疡性结肠炎治疗反应不足或不耐受的患者,在第0、4和8周(诱导研究)接受200 mg静脉注射guselkumab (n=421)或安慰剂(n=280)。在12周时,421例患者中有95例(23%)使用nivolumab + ipilimumab治疗MSI-H结直肠癌。根据CheckMate 8HW iii期试验,nivolumab + ipilimumab可提高微卫星不稳定性高(MSI-H)或错配修复缺陷(dMMR)转移性结直肠癌患者的生存率。Thierry Andre及其同事根据局部检测随机分配不可切除或转移性结直肠癌和MSI-H或dMMR状态的患者,接受纳沃单抗加易普利单抗、纳沃单抗单独或有或没有靶向治疗的化疗。根据一项新的研究,乳糜泻对肠道功能和微生物的影响乳糜泻对肠道功能和微生物组成的影响不会被无麸质饮食所逆转。Carolyn Costigan和同事使用核磁共振成像和粪便样本分析来检查36名新诊断为乳糜泻的患者和相同数量的健康志愿者的肠道功能和微生物组组成。在基线时,乳糜泻患者的小肠水含量明显高于急性严重溃疡性结肠炎患者,肠道运输时间也比联合治疗延迟。根据4期ACTIVE试验,英夫利昔单抗加硫唑嘌呤联合治疗对静脉注射类固醇有反应的急性严重溃疡性结肠炎患者有希望。Aurelien Amiot及其同事将之前未接受过生物制剂或硫嘌呤治疗的患者随机分配到英夫利昔单抗+硫唑嘌呤+ 7天类固醇减量方案(n=32)或硫唑嘌呤+常规标准化类固醇减量方案(n=32)。第52周,治疗
{"title":"Research in Brief","authors":"Holly Baker","doi":"10.1016/s2468-1253(24)00440-0","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00440-0","url":null,"abstract":"&lt;h2&gt;Section snippets&lt;/h2&gt;&lt;section&gt;&lt;section&gt;&lt;h2&gt;Guselkumab for moderately to severely active ulcerative colitis&lt;/h2&gt;Guselkumab is a safe and efficacious treatment option for patients with moderately to severely active ulcerative colitis, according to the &lt;span&gt;&lt;span&gt;phase 3 QUASAR induction and maintenance studies&lt;/span&gt;&lt;svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"&gt;&lt;path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;. David T Rubin and colleagues randomly assigned patients with inadequate response or intolerance to conventional or advanced ulcerative colitis therapy to receive guselkumab 200 mg intravenously (n=421) or placebo (n=280) at weeks 0, 4, and 8 (induction study). At 12 weeks, 95 (23%) of 421 patients in the&lt;/section&gt;&lt;/section&gt;&lt;section&gt;&lt;section&gt;&lt;h2&gt;Nivolumab plus ipilimumab for MSI-H colorectal cancer&lt;/h2&gt;Nivolumab plus ipilimumab increases survival in patients with microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) metastatic colorectal cancer, according to the phase 3 &lt;span&gt;&lt;span&gt;CheckMate 8HW trial&lt;/span&gt;&lt;svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"&gt;&lt;path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;. Thierry Andre and colleagues randomly assigned patients with unresectable or metastatic colorectal cancer and MSI-H or dMMR status according to local testing to receive either nivolumab plus ipilimumab, nivolumab alone, or chemotherapy with or without targeted therapies. In this&lt;/section&gt;&lt;/section&gt;&lt;section&gt;&lt;section&gt;&lt;h2&gt;&lt;span&gt;&lt;span&gt;Impact of coeliac disease on gut function and microbiome&lt;/span&gt;&lt;svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"&gt;&lt;path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;&lt;/h2&gt;Coeliac disease has an impact on gut function and microbiome composition that is not reversed by a gluten-free diet, according to new research. Carolyn Costigan and colleagues used MRI and stool sample analysis to examine gut function and microbiome composition of 36 patients with newly diagnosed coeliac disease and an equal number of healthy volunteers. At baseline, patients with coeliac disease had significantly higher small bowel water content and delayed gut transit times compared with&lt;/section&gt;&lt;/section&gt;&lt;section&gt;&lt;section&gt;&lt;h2&gt;Combination therapy for acute severe ulcerative colitis&lt;/h2&gt;Combination therapy with infliximab plus azathioprine shows promise in patients with acute severe ulcerative colitis responsive to intravenous steroids, according to the &lt;span&gt;&lt;span&gt;phase 4 ACTIVE trial&lt;/span&gt;&lt;svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"&gt;&lt;path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;. Aurelien Am","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"6 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961901","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}
引用次数: 0
Primary intestinal lymphangiectasia 原发性肠淋巴管扩张
IF 35.7 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-01-10 DOI: 10.1016/s2468-1253(24)00438-2
Rahael Ross
No Abstract
没有抽象的
{"title":"Primary intestinal lymphangiectasia","authors":"Rahael Ross","doi":"10.1016/s2468-1253(24)00438-2","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00438-2","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"54 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961903","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}
引用次数: 0
The rise in early-onset colorectal cancer: now a global issue 早发性结直肠癌的上升:现在是一个全球性问题
IF 35.7 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-01-10 DOI: 10.1016/s2468-1253(24)00441-2
No Abstract
没有抽象的
{"title":"The rise in early-onset colorectal cancer: now a global issue","authors":"","doi":"10.1016/s2468-1253(24)00441-2","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00441-2","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"21 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961897","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}
引用次数: 0
Ramadan intermittent fasting for patients with gastrointestinal and hepatobiliary diseases: practical guidance for health-care professionals 胃肠和肝胆疾病患者斋月间歇性禁食:卫生保健专业人员实用指南
IF 35.7 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-01-10 DOI: 10.1016/s2468-1253(24)00283-8
Muhammad Usman, Nasir Javed, Aida Jawhari, Nazim Ghouri, Salman Waqar, Fathima Shah, Saqib Ahmad, Ailsa Hart, Bilal Hameed, Mohammad Qasim Khan, Mohammad Farhad Peerally
Ramadan intermittent fasting can pose challenges and risks for some groups of patients. Based on a narrative literature review and our clinical expertise, we provide practical guidance for clinicians managing patients with gastrointestinal and hepatobiliary conditions who wish to fast during Ramadan. Following the established International Diabetes Federation and Diabetes and Ramadan International Alliance risk stratification framework, we categorised patients’ risk as low or moderate, high, or very high. We advise all patients at very high risk and most patients at high risk to not observe fasting due to potential harm. For others, we offer nuanced recommendations on medication rescheduling, lifestyle changes, and tailored fasting advice to minimise adverse effects. Shared decision making that respects patients’ religious motivations is essential, with risks and benefits carefully weighed on an individual basis.
斋月间歇性禁食会给一些患者群体带来挑战和风险。基于叙述性文献回顾和我们的临床专业知识,我们为临床医生管理希望在斋月期间禁食的胃肠道和肝胆疾病患者提供实用指导。根据已建立的国际糖尿病联合会和糖尿病与斋月国际联盟的风险分层框架,我们将患者的风险分为低或中等、高或非常高。由于潜在的危害,我们建议所有高危患者和大多数高危患者不要禁食。对于其他人,我们提供细致入微的建议,如重新安排药物,改变生活方式,以及量身定制的禁食建议,以尽量减少不良影响。尊重患者宗教动机的共同决策至关重要,并在个人基础上仔细权衡风险和收益。
{"title":"Ramadan intermittent fasting for patients with gastrointestinal and hepatobiliary diseases: practical guidance for health-care professionals","authors":"Muhammad Usman, Nasir Javed, Aida Jawhari, Nazim Ghouri, Salman Waqar, Fathima Shah, Saqib Ahmad, Ailsa Hart, Bilal Hameed, Mohammad Qasim Khan, Mohammad Farhad Peerally","doi":"10.1016/s2468-1253(24)00283-8","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00283-8","url":null,"abstract":"Ramadan intermittent fasting can pose challenges and risks for some groups of patients. Based on a narrative literature review and our clinical expertise, we provide practical guidance for clinicians managing patients with gastrointestinal and hepatobiliary conditions who wish to fast during Ramadan. Following the established International Diabetes Federation and Diabetes and Ramadan International Alliance risk stratification framework, we categorised patients’ risk as low or moderate, high, or very high. We advise all patients at very high risk and most patients at high risk to not observe fasting due to potential harm. For others, we offer nuanced recommendations on medication rescheduling, lifestyle changes, and tailored fasting advice to minimise adverse effects. Shared decision making that respects patients’ religious motivations is essential, with risks and benefits carefully weighed on an individual basis.","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"84 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142961902","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}
引用次数: 0
The case for reducing the use of diagnostic upper and lower gastrointestinal endoscopy 减少诊断性上、下消化道内窥镜使用的案例
IF 35.7 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-01-09 DOI: 10.1016/s2468-1253(24)00428-x
Christopher J Black, Alexander C Ford
No Abstract
没有抽象的
{"title":"The case for reducing the use of diagnostic upper and lower gastrointestinal endoscopy","authors":"Christopher J Black, Alexander C Ford","doi":"10.1016/s2468-1253(24)00428-x","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00428-x","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"35 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936879","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}
引用次数: 0
Tamuzimod in patients with moderately-to-severely active ulcerative colitis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 induction trial Tamuzimod在中度至重度活动性溃疡性结肠炎患者中的应用:一项多中心、双盲、随机、安慰剂对照的2期诱导试验
IF 35.7 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2025-01-07 DOI: 10.1016/s2468-1253(24)00386-8
Bruce E Sands, Remo Panaccione, Geert D'Haens, Stefan Schreiber, Vipul Jairath, Aaron DuVall, Jaroslaw Kierkus, Michael Walczak, Snehal Naik, Kye Gilder, Beatriz Lindstrom, Kathleen Ogilvie, William J Sandborn, Severine Vermeire, David T Rubin, Laurent Peyrin-Biroulet, Silvio Danese
<h3>Background</h3>Tamuzimod (VTX002) is a selective sphingosine 1-phosphate receptor 1 modulator in development for ulcerative colitis. We aimed to assess the safety and efficacy of tamuzimod in patients with moderately-to-severely active ulcerative colitis.<h3>Methods</h3>This double-blind, randomised, placebo-controlled, phase 2 induction trial was conducted at 122 centres across 15 countries in Asia, Europe, and North America. Patients aged 18–80 years with a modified Mayo score (MMS) of 4–9 and an inadequate response or a loss of response, or intolerance to one or more approved ulcerative colitis therapies were randomly assigned (1:1:1) to once-daily oral tamuzimod (60 mg or 30 mg) or placebo for 13 weeks. Randomisation was stratified by previous advanced therapy, baseline corticosteroid, and baseline MMS. The primary endpoint was clinical remission (defined as an MMS stool frequency subscore of ≤1, rectal bleeding subscore of 0, and endoscopic subscore ≤1, excluding friability) at week 13. Adverse events and laboratory abnormalities were assessed for safety. Efficacy and safety analyses included all randomly assigned patients who received at least one study dose, with the efficacy analysis restricted to patients with a baseline MMS of 5–9 based on regulatory feedback. The study 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>NCT05156125</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 EudraCT, 2021-003050-23.<h3>Findings</h3>Between Nov 4, 2021, and Aug 30, 2023, 367 patients were screened, and 213 (mean age 40·6 years [SD 14·2]; 116 [54%] males and 97 [46%] females) were randomly assigned to tamuzimod 60 mg (n=70), tamuzimod 30 mg (n=73), or placebo (n=70). Two in the tamuzimod 30 mg group and two in the tamuzimod 60 mg group with baseline modified Mayo score of 4 were excluded from the efficacy analysis. At week 13, clinical remission was reached by 19 (28%) of 68 patients receiving tamuzimod 60 mg, 17 (24%) of 71 patients receiving tamuzimod 30 mg, and eight (11%) of 70 patients receiving placebo (risk difference 16·5% [95% CI 3·2 to 29·4], p=0·018, for tamuzimod 60 mg <em>vs</em> placebo and 12·5% [–0·2 to 24·9], p=0·041, for tamuzimod 30 mg <em>vs</em> placebo). Treatment-emergent adverse events occurred in 33 (47%) of 70 patients receiving tamuzimod 60 mg, 34 (47%) of 73 patients receiving tamuzimod 30 mg, and 24 (34%) of 70 patients receiving placebo. Most adverse events were mild or moderate. The most frequently reported treatment-emergent adverse events (in ≥5% of in any treatment group) were upper respiratory tract infection (six [9%] of 70 p
tamuzimod (VTX002)是一种用于溃疡性结肠炎的选择性鞘氨醇1-磷酸受体1调节剂。我们的目的是评估tamuzimod在中度至重度活动性溃疡性结肠炎患者中的安全性和有效性。这项双盲、随机、安慰剂对照的2期诱导试验在亚洲、欧洲和北美15个国家的122个中心进行。年龄在18-80岁、改良梅奥评分(MMS)为4-9、对一种或多种已获批准的溃疡性结肠炎治疗反应不足或反应丧失或不耐受的患者被随机分配(1:1:1)至每日一次口服tamuzimod (60mg或30mg)或安慰剂组,持续13周。随机化按先前的高级治疗、基线皮质类固醇和基线MMS分层。主要终点是第13周的临床缓解(定义为MMS大便频率亚评分≤1,直肠出血亚评分为0,内窥镜亚评分≤1,不包括易损性)。对不良事件和实验室异常进行安全性评估。疗效和安全性分析包括所有随机分配的接受至少一个研究剂量的患者,疗效分析仅限于基于监管反馈的基线MMS为5-9的患者。该研究已在ClinicalTrials.gov注册,注册号为NCT05156125, eudraft号为2021-003050-23。在2021年11月4日至2023年8月30日期间,筛选了367例患者,其中213例(平均年龄40.6岁[SD 14.2];116名(54%)男性和97名(46%)女性被随机分配到tamuzimod 60mg (n=70)、tamuzimod 30mg (n=73)或安慰剂组(n=70)。tamuzimod 30 mg组2例,tamuzimod 60 mg组2例,基线改良Mayo评分为4分,被排除在疗效分析之外。在第13周,68名接受他莫兹莫60 mg的患者中有19名(28%)达到临床缓解,71名接受他莫兹莫30 mg的患者中有17名(24%)达到临床缓解,70名接受安慰剂的患者中有8名(11%)达到临床缓解(他莫兹莫60 mg与安慰剂的风险差异为16.5% [95% CI 3.2%至29.4],p= 0.018;他莫兹莫30 mg与安慰剂的风险差异为12.5%[- 0.2%至24.9],p= 0.041)。70例接受他莫齐莫60mg的患者中有33例(47%)发生了治疗后出现的不良事件,73例接受他莫齐莫30mg的患者中有34例(47%)发生了不良事件,70例接受安慰剂的患者中有24例(34%)发生了不良事件。大多数不良事件为轻度或中度。最常报告的治疗不良事件(在任何治疗组中发生率≥5%)是上呼吸道感染(70例患者中60mg tamuzimod组6例[9%],73例tamuzimod 30 mg组1例[1%],70例安慰剂组1例[1%]),贫血(3例[3%],4例[5%]和6例[9%]),头痛(4例[6%],5例[7%]和2例[3%])。未发生房室传导阻滞、心动过缓、黄斑水肿、严重或机会性感染、恶性肿瘤或死亡等不良事件。解释:在溃疡性结肠炎患者中,tamamzimod诱导治疗是有效且耐受性良好的。这些结果和tamuzimod有利的风险-收益特征共同支持tamuzimod用于治疗中度至重度活动性溃疡性结肠炎的持续临床开发。FundingVentyx生物科学。
{"title":"Tamuzimod in patients with moderately-to-severely active ulcerative colitis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 induction trial","authors":"Bruce E Sands, Remo Panaccione, Geert D'Haens, Stefan Schreiber, Vipul Jairath, Aaron DuVall, Jaroslaw Kierkus, Michael Walczak, Snehal Naik, Kye Gilder, Beatriz Lindstrom, Kathleen Ogilvie, William J Sandborn, Severine Vermeire, David T Rubin, Laurent Peyrin-Biroulet, Silvio Danese","doi":"10.1016/s2468-1253(24)00386-8","DOIUrl":"https://doi.org/10.1016/s2468-1253(24)00386-8","url":null,"abstract":"&lt;h3&gt;Background&lt;/h3&gt;Tamuzimod (VTX002) is a selective sphingosine 1-phosphate receptor 1 modulator in development for ulcerative colitis. We aimed to assess the safety and efficacy of tamuzimod in patients with moderately-to-severely active ulcerative colitis.&lt;h3&gt;Methods&lt;/h3&gt;This double-blind, randomised, placebo-controlled, phase 2 induction trial was conducted at 122 centres across 15 countries in Asia, Europe, and North America. Patients aged 18–80 years with a modified Mayo score (MMS) of 4–9 and an inadequate response or a loss of response, or intolerance to one or more approved ulcerative colitis therapies were randomly assigned (1:1:1) to once-daily oral tamuzimod (60 mg or 30 mg) or placebo for 13 weeks. Randomisation was stratified by previous advanced therapy, baseline corticosteroid, and baseline MMS. The primary endpoint was clinical remission (defined as an MMS stool frequency subscore of ≤1, rectal bleeding subscore of 0, and endoscopic subscore ≤1, excluding friability) at week 13. Adverse events and laboratory abnormalities were assessed for safety. Efficacy and safety analyses included all randomly assigned patients who received at least one study dose, with the efficacy analysis restricted to patients with a baseline MMS of 5–9 based on regulatory feedback. The study was registered with &lt;span&gt;&lt;span&gt;ClinicalTrials.gov&lt;/span&gt;&lt;svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"&gt;&lt;path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;NCT05156125&lt;/span&gt;&lt;svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"&gt;&lt;path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"&gt;&lt;/path&gt;&lt;/svg&gt;&lt;/span&gt;, and EudraCT, 2021-003050-23.&lt;h3&gt;Findings&lt;/h3&gt;Between Nov 4, 2021, and Aug 30, 2023, 367 patients were screened, and 213 (mean age 40·6 years [SD 14·2]; 116 [54%] males and 97 [46%] females) were randomly assigned to tamuzimod 60 mg (n=70), tamuzimod 30 mg (n=73), or placebo (n=70). Two in the tamuzimod 30 mg group and two in the tamuzimod 60 mg group with baseline modified Mayo score of 4 were excluded from the efficacy analysis. At week 13, clinical remission was reached by 19 (28%) of 68 patients receiving tamuzimod 60 mg, 17 (24%) of 71 patients receiving tamuzimod 30 mg, and eight (11%) of 70 patients receiving placebo (risk difference 16·5% [95% CI 3·2 to 29·4], p=0·018, for tamuzimod 60 mg &lt;em&gt;vs&lt;/em&gt; placebo and 12·5% [–0·2 to 24·9], p=0·041, for tamuzimod 30 mg &lt;em&gt;vs&lt;/em&gt; placebo). Treatment-emergent adverse events occurred in 33 (47%) of 70 patients receiving tamuzimod 60 mg, 34 (47%) of 73 patients receiving tamuzimod 30 mg, and 24 (34%) of 70 patients receiving placebo. Most adverse events were mild or moderate. The most frequently reported treatment-emergent adverse events (in ≥5% of in any treatment group) were upper respiratory tract infection (six [9%] of 70 p","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"99 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936331","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}
引用次数: 0
期刊
Lancet Gastroenterology & Hepatology
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1