Pub Date : 2024-11-21DOI: 10.1016/s0140-6736(24)02231-1
Maximilian P Schmid, Primoz Petric, Umesh Mahantshetty, Christian Kirisits, Kari Tanderup, Ina Jürgenliemk-Schulz, Jacob Lindegaard, Richard Pötter
No Abstract
无摘要
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<h3>Background</h3>Mirikizumab, a humanised monoclonal antibody that inhibits IL-23p19, is effective in moderate-to-severe ulcerative colitis. We aimed to evaluate the efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn's disease.<h3>Methods</h3>VIVID-1 was a global phase 3, randomised, double-blind, double-dummy, placebo-controlled and active-controlled, treat-through study. The study enrolled adult patients at 324 sites (hospitals or medical centres, clinical practices, and clinical research sites) in 33 countries across Europe, Asia, North America, Central America, South America, and Australia. Adult patients with moderately-to-severely active Crohn's disease and previous inadequate response, loss of response, or intolerance to one or more approved biological therapies or conventional therapies were randomly assigned 6:3:2 to receive mirikizumab 900 mg intravenously at weeks 0, 4, and 8, then 300 mg subcutaneously every 4 weeks from weeks 12 to 52; ustekinumab about 6 mg/kg intravenously at week 0, then 90 mg subcutaneously every 8 weeks from weeks 8 to 52; or placebo. The coprimary endpoints assessing superiority of mirikizumab over placebo were composite endpoints: patient-reported outcome (PRO) clinical response at week 12 and endoscopic response at week 52 (endoscopic response-composite), and PRO clinical response at week 12 and Crohn's Disease Activity Index (CDAI) clinical remission at week 52 (CDAI clinical remission-composite). The adjusted risk differences were calculated, and the comparison was performed by the Cochran–Mantel–Haenszel test. Non-responder imputation was used. VIVID-1 was registered on <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>NCT03926130</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 now complete.<h3>Findings</h3>Between July 23, 2019, and Aug 23, 2023, 1150 patients were randomly assigned and received study treatment (safety population); 1065 patients were included in the efficacy population and received mirikizumab (n=579), ustekinumab (n=287), or placebo (n=199). Both coprimary endpoints were met: endoscopic response-composite was reached in 220 (38·0%) of 579 patients on mirikizumab versus 18 (9·0%) of 199 on placebo (99·5% CI 20·6–36·8; p<0·0001); CDAI clinical remission-composite was reached in 263 (45·4%) of 579 patients on mirikizumab versus 39 (19·6%) of 199 patients on placebo (99·5% CI 15·9–35·6; p<0·0001). The incidence rates of overall adverse events and discontinuations in patients treated with mirikizumab were lower compared with placebo. The most common adverse event across the thr
背景米利珠单抗是一种抑制IL-23p19的人源化单克隆抗体，对中重度溃疡性结肠炎有效。我们的目的是评估米利珠单抗在中重度活动性克罗恩病患者中的疗效和安全性。方法VIVID-1是一项全球性的3期随机、双盲、双假、安慰剂对照和主动对照治疗研究。该研究在欧洲、亚洲、北美洲、中美洲、南美洲和澳大利亚 33 个国家的 324 个研究机构（医院或医疗中心、临床实践机构和临床研究机构）招募成年患者。患有中度至重度活动性克罗恩病且既往对一种或多种获批生物疗法或传统疗法反应不充分、失去反应或不耐受的成年患者被按6:3:2的比例随机分配，在第0、4和8周静脉注射米利珠单抗900毫克，然后从第12周至第52周每4周皮下注射300毫克；在第0周静脉注射乌斯特库单抗约6毫克/千克，然后从第8周至第52周每8周皮下注射90毫克；或安慰剂。评估米利珠单抗优于安慰剂的主要共同终点是复合终点：第12周患者报告结果（PRO）临床反应和第52周内镜反应（内镜反应-复合终点），以及第12周患者报告结果（PRO）临床反应和第52周克罗恩病活动指数（CDAI）临床缓解（CDAI临床缓解-复合终点）。计算调整后的风险差异，并通过 Cochran-Mantel-Haenszel 检验进行比较。采用了非应答者估算方法。VIVID-1在ClinicalTrials.gov上注册，编号为NCT03926130，现已完成。研究结果在2019年7月23日至2023年8月23日期间，1150名患者被随机分配并接受了研究治疗（安全人群）；1065名患者被纳入疗效人群，接受了mirikizumab（n=579）、ustekinumab（n=287）或安慰剂（n=199）治疗。两项主要终点均已达到：579名患者中，220名（38-0%）接受米利珠单抗治疗，199名患者中18名（9-0%）接受安慰剂治疗（99-5% CI 20-6-36-8；p<0-0001）；579名患者中，263名（45-4%）接受米利珠单抗治疗，199名患者中39名（19-6%）接受安慰剂治疗（99-5% CI 15-9-35-6；p<0-0001）。与安慰剂相比，米利珠单抗治疗患者的总体不良事件发生率和停药率较低。三组患者中最常见的不良事件是COVID-19。在接受米利珠单抗治疗的630名患者中，有65人（10-3%）报告了严重不良事件；在接受乌司替尼治疗的309名患者中，有33人（10-7%）报告了严重不良事件；在接受安慰剂治疗的211名患者中，有36人（17-1%）报告了严重不良事件。VIVID-1期间共有3例死亡病例，其中1例死于乌司替尼组，2例死于安慰剂组，包括1例安慰剂无效患者在第12周后转用米利珠单抗。所有死亡病例均与研究药物无关。米利珠单抗在克罗恩病中的安全性符合其已知的良好特性。释义米利珠单抗作为中度至重度活动性克罗恩病患者的诱导和维持治疗是安全有效的，这些患者对标准疗法不耐受、反应不足或失去反应。
{"title":"Efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn's disease: a phase 3, multicentre, randomised, double-blind, placebo-controlled and active-controlled, treat-through study","authors":"Marc Ferrante, Geert D'Haens, Vipul Jairath, Silvio Danese, Minhu Chen, Subrata Ghosh, Tadakazu Hisamatsu, Jaroslaw Kierkus, Britta Siegmund, Sonja Michelle Bragg, Wallace Crandall, Frederick Durand, Emily Hon, Zhantao Lin, Michelle Ugolini Lopes, Nathan Morris, Marijana Protic, Hilde Carlier, Bruce E Sands, Julien Fahed","doi":"10.1016/s0140-6736(24)01762-8","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)01762-8","url":null,"abstract":"<h3>Background</h3>Mirikizumab, a humanised monoclonal antibody that inhibits IL-23p19, is effective in moderate-to-severe ulcerative colitis. We aimed to evaluate the efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn's disease.<h3>Methods</h3>VIVID-1 was a global phase 3, randomised, double-blind, double-dummy, placebo-controlled and active-controlled, treat-through study. The study enrolled adult patients at 324 sites (hospitals or medical centres, clinical practices, and clinical research sites) in 33 countries across Europe, Asia, North America, Central America, South America, and Australia. Adult patients with moderately-to-severely active Crohn's disease and previous inadequate response, loss of response, or intolerance to one or more approved biological therapies or conventional therapies were randomly assigned 6:3:2 to receive mirikizumab 900 mg intravenously at weeks 0, 4, and 8, then 300 mg subcutaneously every 4 weeks from weeks 12 to 52; ustekinumab about 6 mg/kg intravenously at week 0, then 90 mg subcutaneously every 8 weeks from weeks 8 to 52; or placebo. The coprimary endpoints assessing superiority of mirikizumab over placebo were composite endpoints: patient-reported outcome (PRO) clinical response at week 12 and endoscopic response at week 52 (endoscopic response-composite), and PRO clinical response at week 12 and Crohn's Disease Activity Index (CDAI) clinical remission at week 52 (CDAI clinical remission-composite). The adjusted risk differences were calculated, and the comparison was performed by the Cochran–Mantel–Haenszel test. Non-responder imputation was used. VIVID-1 was registered on <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>NCT03926130</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 now complete.<h3>Findings</h3>Between July 23, 2019, and Aug 23, 2023, 1150 patients were randomly assigned and received study treatment (safety population); 1065 patients were included in the efficacy population and received mirikizumab (n=579), ustekinumab (n=287), or placebo (n=199). Both coprimary endpoints were met: endoscopic response-composite was reached in 220 (38·0%) of 579 patients on mirikizumab versus 18 (9·0%) of 199 on placebo (99·5% CI 20·6–36·8; p<0·0001); CDAI clinical remission-composite was reached in 263 (45·4%) of 579 patients on mirikizumab versus 39 (19·6%) of 199 patients on placebo (99·5% CI 15·9–35·6; p<0·0001). The incidence rates of overall adverse events and discontinuations in patients treated with mirikizumab were lower compared with placebo. The most common adverse event across the thr","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1016/s0140-6736(24)02429-2
Marco Zenone, Nora Kenworthy
No Abstract
无摘要
{"title":"Should WHO partner with TikTok to combat misinformation?","authors":"Marco Zenone, Nora Kenworthy","doi":"10.1016/s0140-6736(24)02429-2","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02429-2","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1016/s0140-6736(24)02522-4
Kerri Davidson, Robert Rock, Cyra Levenson, Anna Reisman
No Abstract
无摘要
{"title":"Making the invisible visible: using art to explore the facade of objectivity in medicine","authors":"Kerri Davidson, Robert Rock, Cyra Levenson, Anna Reisman","doi":"10.1016/s0140-6736(24)02522-4","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02522-4","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1016/s0140-6736(24)02554-6
Richard Horton
No Abstract
无摘要
{"title":"Offline: Can public health overcome its colonial history?","authors":"Richard Horton","doi":"10.1016/s0140-6736(24)02554-6","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02554-6","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1016/s0140-6736(24)02520-0
Harriet A Washington
No Abstract
无摘要
{"title":"Meditations on law, race, ownership, and bodies | Patricia J Williams, The Miracle of the Black Leg: Notes on Race, Human Bodies, and the Spirit of the Law, The New Press (2024), p. 256, US$29·99, ISBN: 9781620978160","authors":"Harriet A Washington","doi":"10.1016/s0140-6736(24)02520-0","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02520-0","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1016/s0140-6736(24)02552-2
Udani Samarasekera
No Abstract
无摘要
{"title":"The changing story of access to medicines","authors":"Udani Samarasekera","doi":"10.1016/s0140-6736(24)02552-2","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02552-2","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-21DOI: 10.1016/s0140-6736(24)02374-2
Yousif Ali, Emmanuel Edwar Siddig, Ayman Ahmed
No Abstract
无摘要
{"title":"North Abyei: the humanitarian and health crisis in Sudan","authors":"Yousif Ali, Emmanuel Edwar Siddig, Ayman Ahmed","doi":"10.1016/s0140-6736(24)02374-2","DOIUrl":"https://doi.org/10.1016/s0140-6736(24)02374-2","url":null,"abstract":"No Abstract","PeriodicalId":22898,"journal":{"name":"The Lancet","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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