A Multicenter, Multinational, Randomized, Double-blind, Placebo-controlled Phase 3, Maintenance Study to Evaluate the Efficacy and Safety of Duvakitug in Participants With Moderately to Severely Active Crohn's Disease

This is a multicenter, randomized, double-blind, placebo-controlled, maintenance, Phase 3 study to evaluate the efficacy and safety of duvakitug in participants with moderately to severely active Crohn's Disease (CD). Study details include:
The study duration may be up to 286 weeks including:
* 40-week Pivotal Maintenance Sub-Study
* 240-week Open-Label Extension (OLE) Sub-Study
* 45-day Follow-Up visit
Note: For the participants who do not enroll into OLE Sub-Study, the duration will be up to 46 weeks, including the 40-week maintenance period and a 45-day follow-up visit.
The treatment duration may be up to 280 weeks including:
* 40 weeks in the Pivotal Maintenance Sub-Study
* 240 weeks in OLE Sub-Study
The total number of on-site visits will be up to 43: - 21 visits in the Pivotal Maintenance Sub-Study - 22 visits in the OLE Sub-Study

开始日期2026-01-22

申办/合作机构

Sanofi

[+1]

NCT07185009

/ Recruiting临床3期

A Multicenter, Multinational, Randomized, Double-blind, Placebo-Controlled, Phase 3 Maintenance Study to Evaluate the Efficacy and Safety of Duvakitug in Participants With Moderately to Severely Active Ulcerative Colitis

This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 maintenance study to evaluate the efficacy and safety of duvakitug in participants with moderately to severely active Ulcerative Colitis (UC).
Study details include:
The study duration may be up to 286 weeks including:
* 40-week Pivotal Maintenance Sub-Study
* 240-week Open-Label Extension (OLE) Sub-Study
* 45-day Follow-up Visit Note: For the participants who do not enroll into OLE Sub-Study, the duration will be up to 46 weeks, including the 40-week maintenance period and a 45-day follow-up visit.
The treatment duration may be up to 280 weeks including:
* 40 weeks in Pivotal Maintenance Sub-Study
* 240 weeks in OLE Sub-Study
The total number of on-site visit will be up to 32:
* 21 visits in the Pivotal Maintenance Sub-Study.
* 11 visits in the OLE Sub-Study.

开始日期2026-01-16

申办/合作机构

Sanofi

[+1]

100 项与 Duvakitug 相关的临床结果

登录后查看更多信息

100 项与 Duvakitug 相关的转化医学

登录后查看更多信息

100 项与 Duvakitug 相关的专利（医药）

登录后查看更多信息

项与 Duvakitug 相关的文献（医药）

2026-09-01·The Lancet Gastroenterology & Hepatology

Efficacy and safety of duvakitug in patients with Crohn's disease (RELIEVE UCCD): a phase 2b, randomised, placebo-controlled trial

Article

作者: Duvall, George Aaron ; Barkay, Hadas ; Abrams, Ken ; Singh, Rajendra ; Jairath, Vipul ; Sands, Bruce E ; Danese, Silvio ; Reinisch, Walter ; Levine, Phillip ; Kierkuś, Jaroslaw ; Gross, Nicholas ; Ratiu-Duma, Bogdan

BACKGROUND:

Crohn's disease is a chronic, relapsing inflammatory disease of the gastrointestinal tract. We aimed to assess the efficacy and safety of duvakitug, an anti-TNF-like cytokine 1A monoclonal antibody, in adults with moderately to severely active Crohn's disease.

METHODS:

In this multicentre, placebo-controlled, phase 2b study, we enrolled adults (aged 18-75 years) with moderately to severely active Crohn's disease (including inadequate response, loss of response, or intolerance to previous therapies). We randomly assigned (1:1:1) participants to receive 2250 mg duvakitug loading dose subcutaneously, followed by duvakitug 450 mg or 900 mg every 2 weeks, or placebo loading dose, then placebo every 2 weeks. The primary endpoint, endoscopic response (≥50% reduction from baseline in Simple Endoscopic Score for Crohn's Disease) at week 14, was analysed using Bayesian methodology. A duvakitug dose was declared successful if the posterior probability that the response rate exceeded placebo was at least 0·90. Analyses were done in the modified intention-to-treat population, which included all patients who received at least one dose of their assigned treatment. This trial was registered with ClinicalTrials.gov, NCT05499130, and has been completed.

FINDINGS:

Patients were enrolled from Sept 30, 2022, to Nov 12, 2024. We screened 275 patients with Crohn's disease, of whom 139 (51%) patients were randomly assigned to receive either duvakitug 450 mg (n=46), duvakitug 900 mg (n=47), or placebo (n=46). One patient in the duvakitug 900 mg did not receive study drug; the modified intention-to-treat population therefore included 46 patients in the 450 mg group, 46 in the 900 mg group, and 46 in the placebo group. 78 (57%) patients were previously exposed to at least one advanced therapy. The mean age of enrolled patients was 39·5 years (SD 14·7); 58 (42%) were female, 80 (58%) were male, and 131 (95%) were White. 12 (26%) of 46 patients in the duvakitug 450 mg group, 22 (48%) of 46 in the duvakitug 900 mg group, and six (13%) of 46 in the placebo group had an endoscopic response at week 14. The difference in posterior mean response rates versus placebo was 13% (95% credible interval -3 to 29) for duvakitug 450 mg and 33% (16 to 50) for duvakitug 900 mg, with posterior probabilities of superiority of 0·94 for duvakitug 450 mg and greater than 0·99 for duvakitug 900 mg. Adverse events occurred in 31 (67%) of 46 patients in the duvakitug 450 mg group, 20 (43%) of 46 in the duvakitug 900 mg group, and 22 (48%) of 46 in the placebo group. The most frequent adverse events were nasopharyngitis (two in the 450 mg group, three in the 900 mg group, and three in the placebo group) and headache (four in the 450 mg group, one in the 900 mg group, and one in the placebo group). Serious adverse events occurred in six (13%) patients in the duvakitug 450 mg group, one (2%) in the duvakitug 900 mg group, and five (11%) in the placebo group.

INTERPRETATION:

Duvakitug showed significant evidence for endoscopic response versus placebo in patients with moderately to severely active Crohn's disease, with no safety concerns identified.

FUNDING:

Teva and Sanofi.

2026-09-01·The Lancet Gastroenterology & Hepatology

Efficacy and safety of duvakitug in patients with ulcerative colitis (RELIEVE UCCD): a phase 2b, randomised, placebo-controlled trial

Article

作者: Reinisch, Walter ; Barkay, Hadas ; Abrams, Ken ; Singh, Rajendra ; Stepek, David ; Sands, Bruce E ; Danese, Silvio ; Levine, Phillip ; Kempinski, Radoslaw ; Gross, Nicholas ; Jairath, Vipul ; Ratiu-Duma, Bogdan

BACKGROUND:

Ulcerative colitis is a chronic inflammatory disease affecting the colon and rectum. We aimed to investigate the efficacy and safety of duvakitug, an anti-TNF-like cytokine 1A (TL1A) monoclonal antibody, in adults with moderately to severely active ulcerative colitis.

METHODS:

In this multicentre, placebo-controlled, phase 2b study, we randomly assigned (1:1:1) adults aged 18-75 years with moderately to severely active ulcerative colitis (including patients with inadequate response, loss of response, or intolerance to previous conventional or advanced therapies) to receive a 2250 mg loading dose of duvakitug (subcutaneously), followed by either 450 mg or 900 mg doses every 2 weeks, or placebo loading dose followed by placebo every 2 weeks. The primary endpoint was clinical remission (modified Mayo score) at week 14, analysed using Bayesian methodology. A duvakitug dose was declared successful if the posterior probability that the response rate exceeded placebo was 0·90 or greater. Analyses were done in the modified intention-to-treat population, which included all patients who received at least one dose of their assigned treatment. This trial was registered with ClinicalTrials.gov, NCT05499130, and has been completed.

FINDINGS:

Patients were enrolled between Sept 30, 2022 and Nov 12, 2024. We screened 260 patients with ulcerative colitis. Of these, we randomly assigned 137 (53%) patients to receive duvakitug (n=47 450 mg and n=46 900 mg) or placebo (n=44; modified intention-to-treat analysis set). Patients had a mean age of 41·0 years (SD 13·1); 86 (63%) were men, 51 (37%) were women, and 132 (96%) were White. 43 (31%) patients had previous exposure to an approved advanced therapy. 17 (36%) of 47 patients in the duvakitug 450 mg group and 22 (48%) of 46 patients in the duvakitug 900 mg group were in clinical remission at week 14, compared with nine (20%) of 44 patients in the placebo group. Differences in posterior mean response rates versus placebo were 15% (95% credible interval [CrI] -3 to 33) for duvakitug 450 mg and 26% (95% CrI 8 to 44) for duvakitug 900 mg, with posterior probabilities of superiority to placebo exceeding the prespecified threshold for declaring efficacy (0·95 in the 450 mg group and >0·99 in the 900 mg group). Adverse event incidence was similar with duvakitug (23 [49%] of 47 patients in the 450 mg group and 20 [43%] of 46 in the 900 mg group) and placebo (23 [52%] of 44). The most frequently occurring adverse events were anaemia (one in the 450 mg group, one in the 900 mg group, and three in the placebo group) and upper respiratory tract infection (three in the 450 mg group, one in the 900 mg group, and one in the placebo group). One serious adverse event occurred in the 900 mg group (non-infective oophoritis) and one in the placebo group (intracranial haemorrhage).

INTERPRETATION:

Duvakitug showed significant evidence for clinical remission versus placebo, with no safety concerns identified, in patients with moderately to severely active ulcerative colitis.

FUNDING:

Teva and Sanofi.

2026-06-01·ALIMENTARY PHARMACOLOGY & THERAPEUTICS

Review Article: TL1A Inhibitors in IBD ‐ Mechanistic Rationale and Clinical Evidence

Review

作者: Sharma, Vishal ; Goyal, Manjeet Kumar ; Sehgal, Tanisha ; Sebastian, Shaji ; Srivastava, Harsh ; Bishu, Shrinivas

ABSTRACT:

Background:

Tumour necrosis factor‐like ligand 1A (TL1A) and its receptor DR3 form a pivotal signalling dyad linking immune activation, epithelial barrier dysfunction and fibrogenesis in inflammatory bowel diseases. (IBD).

Aims:

This narrative review summarizes the molecular biology of the TL1A–DR3 axis, its roles in intestinal inflammation, fibrosis, and extraintestinal manifestations, and the emerging therapeutic landscape of TL1A inhibition in IBD.

Methods:

Narrative synthesis of preclinical, translational, and clinical literature on TL1A/DR3 in Crohn's disease and ulcerative colitis.

Results:

TL1A overexpression drives Crohn's‐like ileitis, barrier disruption, and fibrosis in models; blockade attenuates both inflammation and remodelling. TL1A inhibitors show clinical/endoscopic remission in early‐phase moderate–severe IBD trials (e.g., tulisokibart, duvakitug), with phase 3 programs ongoing.

Conclusion:

TL1A–DR3 integrates mucosal immunity with stromal injury, positioning inhibitors as a novel class to overcome IBD therapeutic ceilings by targeting the inflammation‐fibrosis continuum.

231

项与 Duvakitug 相关的新闻（医药）

2026-09-01

·微信

仿制药之王Teva ，新药放量驱动三年股价涅槃上行

作为全球仿制药领域的龙头企业，Teva（梯瓦制药）正依托Pivot to Growth战略加速转型，由传统仿制药巨头向创新驱动的生物制药企业迈进。股价走势如下：公司的转型战略包含四大核心支柱：释放现有增长引擎势能、加码内部创新研发、筑牢仿制药业务基本盘和优化业务组合聚焦高价值赛道。从收入结构可以清晰看到转型成效，2022年创新药仅占总营收9%，预计2026年占比提升至22%；非创新业务营收呈小幅负增长，整体公司营收实现中个位数复合增长，毛利率持续抬升，目标到2030年整体毛利率突破60%。公司还在同步推进业务优化，计划剥离AP原料药业务，精简低效资产，把资源更多的向创新与高附加值生物类似药倾斜。 2026全年指引总收入165~168.5亿美元，自由现金流维持20~24亿美元，资金将持续反哺创新管线的推进。 01 成熟创新产品：三大核心产品成为增长主引擎 AUSTEDO（Deutetrabenazine，氘丁苯那嗪）、UZEDY（Risperidone，利培酮）、AJOVY（Fremanezumab‑vfrm，夫瑞奈珠单抗）三款商业化创新药构成Teva当下的业绩支柱，2026年第二季度三款产品合计同比增长43%，全部上调全年收入指引，神经、偏头痛两大赛道优势持续放大。 AUSTEDO用于迟发性运动障碍、亨廷顿舞蹈症，同时拥有普通片与长效缓释剂型AUSTEDO XR。2026年第二季度全球收入6.96亿美元，同比增长40%；美国市场收入6.76亿美元，同比大涨37%，AUSTEDO XR在新患者中渗透率超过60%，长效版本被越来越多VMAT2靶点处方医生采纳。Teva将2026全年收入指引上调至24.5~26亿美元，预计峰值销售超过30亿美元。 UZEDY缓释注射混悬液是针对精神分裂症的长效注射剂（LAI），也是目前唯一无需监测的每月一次皮下注射奥氮平长效制剂。2026年第二季度实现7700万美元收入，同比增长43%，是非典型长效针剂中增速最快品种，每月新增处方医生超800位。全年收入指引上调至2.7~2.9亿美元，未来和在研Olanzapine LAI（奥氮平长效注射剂）共同构筑精神分裂症长效针剂产品矩阵。 AJOVY是CGRP靶点偏头痛预防药物，2026年第二季度全球净销售额2.44亿美元，同比增长56%，在全球超半数市场成为注射型α‑CGRP抑制剂第一名。欧洲市场实现22%滚动年度增长，国际市场依靠合作伙伴贡献了可观增量，全年收入指引上调至8.5~8.7亿美元，产品峰值销售有望接近10亿美元。 02 后期管线：神经科学与免疫学双线并进 Teva搭建了覆盖从临床前到申报阶段的丰富管线，重点布局神经科学与免疫学两大板块。 01 神经科学管线 ecopipam（EBS‑101）是一款全球first‑in‑class选择性D1受体拮抗剂，用于治疗儿童抽动秽语综合征。2026年6月，Teva以7亿美元首付款收购Emalex Biosciences获得该分子。最新临床数据显示，相比安慰剂，该药物12周内复发风险降低53%，66%患者在临床试验3期后续研究中完成一年治疗，抽动症状持续改善。目前已向FDA递交了NDA，预计2027年获批。 Olanzapine LAI（奥氮平长效注射剂）是一款针对精神分裂症的皮下每月给药制剂，欧盟MAA申请已获受理，FDA预计2026第四季度给出审评结果，与已经上市的UZEDY形成长效针剂产品梯队，强化精神疾病领域布局。 emrusolmin目前针对多系统萎缩（MSA）进行研发，已获得FDA快速通道与孤儿药资格，计划2028年争取加速路径递交上市申请。 02 免疫学管线 duvakitug（抗TL1A）是Teva的核心自身免疫资产，与赛诺菲合作开发，TL1A靶点具备抗炎、潜在抗纤维化双重潜力，有望覆盖炎症以及纤维化驱动的消化道、皮肤疾病。目前正在开展针对溃疡性结肠炎、克罗恩病的临床试验3期研究，同时还在拓展化脓性汗腺炎（HS）、纤维狭窄型克罗恩病（FSCD）新适应症，计划2026年第四季度完成临床试验2期研究首例患者入组。双重作用哮喘救援吸入剂（DARI，ICS-SABA）针对中重度哮喘，兼顾抗炎与支气管扩张双重作用。临床试验3期研究入组已完成，预计2026年底完成主要终点。抗IL‑15同时布局白癜风与乳糜泻两大适应症。其中，针对白癜风的临床试验1b期研究数据显示，每12周皮下注射，24周面部皮损改善率数据与在研JAK抑制剂相当，已经推进临床试验2b期研究；针对乳糜泻适应症的临床试验2a期活检终点数据预计2026下半年读出，IL‑15抑制有望修复乳糜泻受损肠道绒毛结构。另外，Teva还有抗PD‑1/IL‑2等早期免疫分子，计划2026下半年对外披露输出首次人体临床数据，持续丰富早期创新储备。 03 生物类似药：构筑仿制药业务第二增长曲线仿制药业务依然是Teva重要的现金来源，为创新研发提供资金支持，但受来那度胺仿制药销售下滑影响，2026年第二季度全球仿制药收入同比下滑15%，美国市场承压明显，欧洲市场保持稳健，国际市场小幅增长。生物类似药势头强劲，2026年6月，Teva在欧洲推出了Eylea的生物类似药AHZANTIVE（aflibercept）；2026年7月，还与Polpharma Biologics达成了全球许可协议，拟开发Ocrevus（ocrelizumab）生物类似药。 Teva将生物类似药作为仿制药板块重要增长点，依托外部合作持续扩充产品线。目前已有15款生物类似药实现商业化，2027~2031年还将有多款重磅品种陆续递交申报与上市，覆盖维得利珠单抗、帕博利珠单抗、纳武利尤单抗、奥瑞珠单抗等多款原研重磅产品，合作方包括Alvotech、mAbxience、Polpharma等企业。在美国，已有2款上市生物类似药取得细分市场第一名；欧盟在2026上半年已经推出3款生物类似药，进一步放大了低成本生物药可及性，后续为公司贡献稳定现金流。 04 结语 Teva正在完成一场深刻的企业重塑，仿制药业务提供稳定现金流，生物类似药拓展仿制药价值边界；已经商业化的AUSTEDO、UZEDY、AJOVY构筑了短期业绩底座；ecopipam、duvakitug、抗IL‑15等后期管线打开中长期增长天花板。当然转型依旧面临多重挑战，仿制药板块受原研专利到期节奏、价格竞争压力；众多后期管线仍需要通过监管机构审批，临床结果存在不确定性；并购资产ecopipam商业化成效仍有待观察。如果管线资产能够按预期推进，Teva有望彻底摆脱传统仿制药企业标签，成长为神经、自身免疫领域具备全球竞争力的创新生物制药企业。

2026-08-31

·微信

柳叶刀·胃肠病学与肝病学 11卷 7-9期

THE LANCET Gastroenterology & Hepatology. Volume 11Number7 柳叶刀·胃肠病学与肝病学 11卷 7期 https://www.thelancet.com/journals/langas/issue/current Editorial（社论） 1 Rome V: refining the language of gut–brain disorders 罗马Ⅴ：完善肠–脑疾病的术语体系 The Lancet Gastroenterology & Hepatology The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p541 Comment（述评） 2 A changing HIV treatment landscape: what does lenacapavir mean for people living with HBV? HIV治疗格局之变：来那卡帕韦对HBV感染者意味着什么？ Philippa C Matthews,Marion Delphin,Motswedi Anderson,Joanna Redmond,Stuart Flanagan,Maryam Shahmanesh The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p542 3 Alaska Native peoples and colorectal cancer: opportunities for research and prevention 阿拉斯加原住民与结直肠癌：研究与预防的机遇 Diana Redwood,LaRita Laktonen-Ward,Elena Roik The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p544 4 Breaking the cycle: from documenting data scarcity to enabling global IBD research 打破循环：从记录数据匮乏到推动全球IBD研究 Mohammed Nabil Quraishi,Badr Al-Bawardy,Rupa Banerjee,Maiara Brusco De Freitas,David Epstein,Tine Jess The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p546 Correspondence（读者来信） 5 Cyclic exclusive enteral nutrition in paediatric Crohn's disease 儿童克罗恩病的周期性全肠内营养 Aaron S Bancil,Edward M Giles,Jessica Fitzpatrick The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p550 6 Cyclic exclusive enteral nutrition in paediatric Crohn's disease – Authors’ reply 儿童克罗恩病的周期性全肠内营养——作者回复 Bénédicte Pigneur,Frank M Ruemmele The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p550 7 Upfront medical or surgical treatment in Crohn's disease 克罗恩病的初始药物治疗还是手术治疗 Nurulamin M Noor,Phillip R Fleshner,Gil Y Melmed,Corey A Siegel The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p551 8 Upfront medical or surgical treatment in Crohn's disease – Authors’ reply 克罗恩病的初始药物治疗还是手术治疗——作者回复 Lotte Oldenburg,Anouck E G Haanappel,Geert R D’Haens,Willem A Bemelman The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p552 9 Cirrhotic cardiomyopathy and portal hypertension: addressing the full disease spectrum in heart–liver co-management 肝硬化心肌病与门静脉高压：在心–肝协同治疗中关注完整疾病谱 Madeleine Gill,Geoffrey W McCaughan,Anoop N Koshy,John F O’Sullivan,Avik Majumdar The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p553 Corrections（勘误） 10 Correction to Lancet Gastroenterol Hepatol 2026; 11: 355–66 勘误：柳叶刀·胃肠病学与肝病学 2026; 11: 355–66 The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：e9 11 Correction to Lancet Gastroenterol Hepatol 2026; 11: 557–69 勘误：柳叶刀·胃肠病学与肝病学 2026; 11: 557–69 The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：e9 News（新闻） 12 Digestive Disease Week 2026 2026年消化疾病周 Bethany Gomersall The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p555 In Focus（焦点） Theatre（剧场） 13 Wee, Poo, Snot: harnessing bodily functions to inspire budding scientists 尿液、粪便、鼻涕：利用身体功能激发未来科学家的兴趣 Peter Ranscombe The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p556 Articles（论著） 14 Adjuvant chemoradiotherapy versus completion total mesorectal excision after local excision for early rectal cancer (TESAR): a multicentre, randomised, controlled, phase 3, non-inferiority trial 辅助放化疗与局部切除后完全全直肠系膜切除术治疗早期直肠癌（TESAR）：一项多中心、随机、对照、3期、非劣效性试验 Laura R Moolenaar,Mahsoem Ali,Theo J Aufenacker,Geerard L Beets,Robbert J I Bosker,Tineke E Buffart,Jacobus WA Burger,Evelien Dekker,Quentin Denost,Pascal G Doornebosch,Peter van Duijvendijk,Hans F J Fabry,Elisabeth D Geijsen,Michael F Gerhards,Wilhelmina M U van Grevenstein,Brechtje A Grotenhuis,Christiaan Hoff,Jeroen W A Leijtens,Koen C M J Peeters,Apollo Pronk,George P van der Schelling,Colin Sietses,Anke B Smits,Boudewijn R Toorenvliet,Anthony W H van de Ven,Emiel G G Verdaasdonk,Ronald J C L M Vuylsteke,Henderik L van Westreenen,Johannes H W de Wilt,David D E Zimmerman,Marilyne M Lange,Nicole C T van Grieken,Barbara A J Bastiaansen,Roel Hompes,Corrie A Marijnen,Marcel G W Dijkgraaf,Leon M G Moons,Pieter J Tanis,Chris Cunningham,J B Tuynmanon behalf of the TESAR Study Group The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p557 15 Effect of one or two cycles of dual immunotherapy with nivolumab and ipilimumab in patients with mismatch repair-deficient rectal cancer (RESET-R): interim results from a multicentre, single-arm, phase 2 trial 纳武利尤单抗联合伊匹木单抗双免疫治疗一或两个周期对错配修复缺陷型直肠癌患者的疗效（RESET-R）：一项多中心、单臂、2期试验的中期结果 Line Schmidt Tarpgaard,Laurids Østergaard Poulsen,Ismail Gögenur,Tobias Freyberg Justesen,Søren Rafael Rafaelsen,Nadia Øgaard,Christina Demuth,Claus Lindbjerg Andersen,Lise Ventzel,Pernille Øhlenschläger Larsen,Anne Ramlov,Ken Ljungmann,Michael Bødker Lauritzen,Laura Vittrup Diness,Jakob Lykke,Vinicius Araújo Barbosa de Lima,Søren Kjær,Søren Salomon,Per Vadgaard Andersen,Per Pfeiffer The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p570 16 The small interfering RNA imdusiran as single and multiple doses in healthy, randomised individuals and non-randomised individuals with chronic hepatitis B (AB-729–001): a phase 1a/b trial 小干扰RNA imdusiran（药物名称）在健康随机个体及慢性乙型肝炎非随机个体中单次及多次给药的研究（AB-729–001）：一项1a/b期试验 Man-Fung Yuen,Edward Gane,Jacinta A Holmes,Simone I Strasser,Apinya Leerapun,Wattana Sukeepaisarnjaroen,Pisit Tangkijvanich,Elina Berliba,Alina Jucov,Yoon Jun Kim,Young-Suk Lim,Emily P Thi,Timothy Eley,Kevin R Gray,Elina Medvedeva,Varun Sharma,Christine Espiritu,Sharie C Ganchua,Bhavna S Paratala,Christina Iott,Heather Sevinsky,Tiffany Fortney,Mark Anderson,Gavin A Cloherty,Michael J Sofia,Ganapati Reddy Pamulapati,Amy C H Lee,Gastón Picchio,Karen D Sims The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p579 17 Intestinal ultrasound to detect postoperative recurrence in patients with Crohn's disease: an international, multidisciplinary, RAND/UCLA appropriateness method study 肠道超声检测克罗恩病术后复发：一项国际多学科RAND/UCLA适宜性方法研究 Christopher Ma,Siwar Albashir,Mariangela Allocca,Anthony de Buck van Overstraeten,Paulo G Kotze,Cathy Lu,Christian Maaser,Giovanni Maconi,Remo Panaccione,Miguel Regueiro,Jordi Rimola,Antonino Spinelli,Stuart A Taylor,Rune Wilkens,Willem Bemelman,Noa Krugliak Cleveland,Krisztina B Gecse,Susan Archer,Soushyant Kiarasi,Linda J Cornfield,Kerri L Novak The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p602 Review（综述） 18 The use of pharmacotherapies in non-cirrhotic metabolic dysfunction-associated steatohepatitis: a UK expert consensus 非肝硬化代谢功能障碍相关脂肪性肝炎的药物治疗：英国专家共识 Jeremy F Cobbold,Hamish Miller,Kate Hallsworth,Pinelopi Manousou,Thomas Marjot,Michael E D Allison,Quentin M Anstee,Matthew J Armstrong,Leah Avery,Vian Azzu,Paul N Brennan,Christopher D Byrne,Tessa M Cacciottolo,Lynsey Corless,Daniel Forton,Timothy Hardy,Vanessa Hebditch,Helen Jarvis,Wenhao Li,Dina Mansour,Stuart McPherson,Yensiew Miao,Joanne Morling,Ashis Mukhopadhya,Benjamin Mullish,Richard Parker,Imran Patanwala,Jay Patel,Michael Pavlides,Tina Reinson,Ian A Rowe,Francesca Saffioti,Faisal Shaikh,Ankur Srivastava,Nwe Ni Than,Emmanuel Tsochatzis,Edvard Volcek,Jeremy W Tomlinson,William Alazawi The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p616 19 Management of colorectal cancer in older adults: an expert panel recommendation to guide daily clinical practice 老年结直肠癌的治疗：指导日常临床实践的专家组建议 Gabor Liposits,Thierry André,Thomas Aparicio,Isacco Montroni,Julien Taieb,Claire Gallois,Eric Van Cutsem,Michel Ducreux,Per Pfeiffer,Sara Lonardi,Geerard L Beets,Karin Haustermans,Naureen Starling,Gerald W Prager,Gunnar Folprecht,Demetris Papamichael The Lancet Gastroenterology & Hepatology. Jul 2026, Vol 11(7)：p627 THE LANCET Gastroenterology & Hepatology. Volume 11Number 8 柳叶刀·胃肠病学与肝病学 11卷 8期 https://www.thelancet.com/journals/langas/issue/current Editorial（社论） 1 Drugging the undruggable in pancreatic cancer 攻克胰腺癌中“不可成药”靶点的药物研发 The Lancet Gastroenterology & Hepatology The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p645 Comment（述评） 2 Effect of repeated elastography measurements in LiverScreen 肝脏筛查项目中重复弹性检测的临床价值 Hannes Hagström,Ying Shang The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p646 3 Metabolic syndrome myopathy: defining an emerging clinical entity in patients with MASLD 代谢综合征肌病：代谢相关脂肪性肝病患者一类新兴临床疾病的确立 Melinda Wang,Jennifer C Lai The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p647 4 All in her head: dismantling medical misogyny in disorders of gut–brain interaction 一切皆源于主观臆症：破除肠脑互动疾病诊疗中的医学厌女偏见 Tiffany H Taft,Tina Aswani-Omprakash,Johannah Ruddy The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p650 Correspondence（读者来信） 5 COLOR III: widespread TaTME dissemination demands a LAPCO-equivalent framework COLOR III研究：经肛全直肠系膜切除术广泛推广亟需建立等同腹腔镜结直肠手术协作组的规范体系 Shazad Q Ashraf,Andrew D Beggs The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p653 6 The spectrum of steatotic liver disease in the USA 美国脂肪性肝病疾病谱 Kartik Jaidka,Naveen Bhagat,Arka De,Ajay Duseja The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p653 7 The spectrum of steatotic liver disease in the USA 美国脂肪性肝病疾病谱 Hans Scherübl The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p654 8 The spectrum of steatotic liver disease in the USA – Authors’ reply 《美国脂肪性肝病疾病谱》——作者答复 James M Paik,Zobair M Younossi The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p655 9 Lessons from a ransomware crisis and its effect on adult liver transplant services 勒索软件网络危机及其对成人肝移植诊疗服务的影响与启示 Abdul Rahman Hakeem,Karen Mercer,Bu Hayee,Oliver Long,Abid Suddle,Wayel Jassem,Parthi Srinivasan,Krishna Menon,Anneliese Rigby,Miriam Cortes-Cerisuelo,Varuna Aluvihare The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p655 Corrections（勘误） 10 Correction to Lancet Gastroenterol Hepatol 2025; 10: 998–1012 《柳叶刀-胃肠病学与肝病学》2025年第10卷998–1012页文章勘误 The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：e10 11 Correction to Lancet Gastroenterol Hepatol 2026; 11: 546–49 《柳叶刀-胃肠病学与肝病学》2026年第11卷546–549页文章勘误 The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：e10 News（新闻资讯） 12 EASL Congress 2026 2026年欧洲肝脏研究协会年会 Rob Brierley The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p658 13 Research in Brief 研究简讯 Holly Baker The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p659 Articles（论著） 14 HLA-DRB1*01:03 in patients with inflammatory bowel disease: a genotype–phenotype association study 炎症性肠病患者HLA-DRB1*01:03基因型：基因型-表型关联研究 Qian Zhang,Eathar Shakweh,Mohmmed Tauseef Sharip,Benjamin Zare,Christopher Roberts,Nicola J Wyatt,Jennifer Clough,Claire Bewshea,Omar El Garwany,Robert Lees,Saima Mukhtar,Hameed Rehman,Hollie Thistle,Robert Mulligan,Melanie Taylor,Parizade Raymode,Benjamin Hamilton,Nurulamin M Noor,Francesco Morda,Madeleine Taylor,Mina Gyanwali,Ogwa Tobi,Stefanos Kateroglou,Sean Von Hagt,UK IBD Genetics Consortium,NIHR IBD BioResource,Shaji Sebastian,Ailsa Hart,Laura Keylock,Laetitia Pele,Charlie W Lees,Tim Raine,Christopher A Lamb,Carl A Anderson,Tariq Ahmad,Holm Uhlig,Miles Parkes,Laura Fachal,Nicholas A Kennedy,James C Lee The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p660 15 Dupilumab versus placebo in adults and adolescents with eosinophilic gastritis (DEGAS): a double-blind, placebo-controlled, phase 2, multicentre, randomised controlled trial 度普利尤单抗对比安慰剂治疗成人及青少年嗜酸性粒细胞性胃炎（DEGAS研究）：一项Ⅱ期、双盲、安慰剂对照、多中心随机对照临床试验 Nirmala P Gonsalves,Evan S Dellon,Kara L Kliewer,Tetsuo Shoda,Regina Yearout,Seema S Aceves,Nicoleta C Arva,John A Besse,Julie M Caldwell,Mirna Chehade,Amaziah Coleman,Margaret H Collins,Sara Anvari,Gary W Falk,Sandeep K Gupta,Girish Hiremath,David A Katzka,Paneez Khoury,John Leung,Calies Menard-Katcher,Paul Menard-Katcher,Kathryn A Peterson,Maria A Pletneva,Amanda K Rudman Spergel,Jonathan M Spergel,Tatyana Vaysman,Joshua B Wechsler,Benjamin L Wright,Guang-Yu Yang,Xue Zhang,Meijian Zhou,Ashish Bansal,Bram P Raphael,Amr Radwan,Jennifer Maloney,Antonio Martin,Yamo Deniz,Glenn T Furuta,Lisa J Martin,Marc E Rothenbergfor The Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) Investigators The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p672 16 Liver stiffness dynamics in European populations (LiverScreen): a longitudinal, multicentre, prospective, population-based cohort study 欧洲人群肝脏硬度动态变化研究（肝脏筛查项目）：一项基于人群、多中心、前瞻性纵向队列研究 Jesse Pustjens,Katrine Tholstrup Bech,Guillem Pera,Laurens A van Kleef,Helle Lindholm Schnefeld,Robert J de Knegt,Sarwa Darwish Murad,Harry L A Janssen,Peter Andersen,Johanne Kragh Hansen,Llorenç Caballeria,Carla Chacon,Ingrid Arteaga,Pere Toran,Anita Arslanow,Anna Soria,Marta Cervera,Aleksander Krag,Isabel Graupera,Pere Ginès,Willem Pieter Brouwer,Maja Thieleon behalf of the LiverScreen Consortium Investigators The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p689 17 Addition of ipilimumab to atezolizumab plus bevacizumab in advanced hepatocellular carcinoma (PRODIGE 81-FFCD 2101-TRIPLET HCC): phase 2 results from a randomised, multicentre, open-label, phase 2–3 trial 阿替利珠单抗联合贝伐珠单抗基础上加用伊匹木单抗治疗晚期肝细胞癌（PRODIGE 81-FFCD 2101-TRIPLET HCC研究）：一项多中心、开放标签Ⅱ/Ⅲ期随机临床试验Ⅱ期研究结果 Philippe Merle,Jean-Frederic Blanc,Karine Le Malicot,Jean-Marie Peron,Vincent Bourgeois,Mohamed Bouattour,Yann Touchefeu,Carole Vitellius,Faiza Khemissa Akouz,Alexandra Heurgué,Paul Girot,Eric Assenat,Eric Nguyen-Khac,Jean-Pierre Bronowicki,Juliette Viaud,Meher Ben Abdelghani,Sylvain Manfredi,Julien Edeline,Jean-Marc Phelipfor the TRIPLET-HCC study investigators The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p700 Viewpoint（观点） 18 Breaking the therapeutic ceiling in inflammatory bowel disease: myth or reality? 突破炎症性肠病治疗瓶颈：空想还是现实？ Virginia Solitano,Vipul Jairath,Fernando Magro,Alessandro Armuzzi,Laurent Peyrin-Biroulet,Silvio Danese The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p713 19 Balancing benefit and burden: rethinking post-polypectomy colonoscopy surveillance strategies 权衡获益与医疗负担：重新思考息肉切除术后结肠镜随访监测策略 Joep E G IJspeert,Michael Bretthauer,Rodrigo Jover,Evelien Dekkeron behalf of the Dutch colonoscopy surveillance working group The Lancet Gastroenterology & Hepatology. Aug 2026, Vol 11(8)：p720 THE LANCET Gastroenterology & Hepatology. Volume 11Number 9 柳叶刀·胃肠病学与肝病学 11卷 9期 https://www.thelancet.com/journals/langas/issue/current Editorial（社论） 1 A decade in gastroenterology and hepatology 胃肠病学与肝病学十年回顾 The Lancet Gastroenterology & Hepatology The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p727 Comment（评述） 2 Low‑dose aspirin: effective cancer chemoprevention in Lynch syndrome 低剂量阿司匹林：林奇综合征有效的癌症化学预防方案 Kevin J Monahan The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p728 3 RELIEVE UCCD: one pathway, two diseases, and a glimpse into the future of IBD trial design RELIEVE‑UCCD研究：同一条通路、两类疾病，窥探炎症性肠病临床试验设计的未来方向 Bram Verstockt The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p729 4 Combination therapy in metabolic dysfunction‑associated steatohepatitis 代谢功能障碍相关脂肪性肝炎的联合治疗 Oren Shibolet,Helena Katchman The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p732 5 The central role of primary care in liver health 基层医疗在肝脏健康管理中的核心作用 Rob Brierley,Hugh Thomas The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p733 6 A decade in inflammatory bowel disease: progress, plateaus, and perspectives 炎症性肠病十年发展：进展、瓶颈与展望 Britta Siegmund The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p735 7 A decade of transformation in MASLD: from nomenclature to novel therapies 代谢功能障碍相关脂肪性肝病十年变革：从命名更新到新型疗法 Jörn M Schattenberg,Mazen Noureddin The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p737 8 Dietary management of gastrointestinal disease: progress over the last decade and opportunities for the next 胃肠道疾病的膳食干预：近十年进展与未来机遇 Kevin Whelan,Heidi M Staudacher The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p738 9 The decade that changed hepatocellular carcinoma: shaping a new treatment paradigm 改写肝细胞癌诊疗格局的十年：构建全新治疗模式 Antonio D’Alessio,Antonella Cammarota,Stephen L Chan,Lorenza Rimassa The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p741 10 Ten years of advances in disorders of gut–brain interaction 肠‑脑互动相关疾病十年研究进展 Alexander C Ford,Nicholas J Talley The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p743 11 Progress and prospects in viral hepatitis elimination 病毒性肝炎消除工作的进展与前景 C Wendy Spearman,Mark W Sonderup The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p745 12 A decade of progress in cholestatic liver diseases: navigating a new era 胆汁淤积性肝病十年进展：迈入全新发展阶段 Vincenzo Ronca,Maria Buzias,Ana Lleo The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p748 13 Translating the gut microbiome: where are we? 肠道微生物组的临床转化：当下发展现状 Jeroen Raes The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p750 14 A decade of artificial intelligence in endoscopy: from proof of concept to clinical reality 人工智能内镜应用十年：从概念验证走向临床落地 Masashi Misawa,Yuichi Mori The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p752 15 A decade of diversity, equity, and inclusion in gastroenterology and hepatology: a US perspective 胃肠肝病领域多元、公平与包容建设十年——美国视角 Pascale M White,Nikki Duong,Laura E Targownik,Sophie Balzora The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p754 Correspondence（通信） 16 Therapeutic drift or formulation drift: avoiding misconceptions about rifaximin and antimicrobial resistance in cirrhosis 药效偏移还是制剂差异：厘清肝硬化患者利福昔明与抗菌耐药性的认知误区 Carmelo Scarpignato,Manuel Romero‑Gómez The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p757 17 Therapeutic drift or formulation drift: avoiding misconceptions about rifaximin and antimicrobial resistance in cirrhosis –Authors' reply 药效偏移还是制剂差异：厘清肝硬化患者利福昔明与抗菌耐药性的认知误区——作者回复 Rajiv Jalan,Vishal C Patel,Saeed Shoaie The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p758 18 Ethnicity, diversity, and inclusion in gastroenterology: from representation to system performance 胃肠病学领域种族、多元与包容建设：从人员覆盖到体系效能 Ajay M Verma,Debbie L Shawcross,Neeraj Bhala The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p758 Articles（论著） 19 Aspirin for cancer prevention in individuals with Lynch syndrome: first results from the CaPP3 multicentre, randomised, double‑blind, non‑inferiority trial 阿司匹林用于林奇综合征人群癌症预防：CaPP3多中心随机双盲非劣效性试验初步结果 John Burn,Gillian M Borthwick,Faye Elliott,Finlay Macrae,Kai Ren Ong,Alison C Kraus,Nadir Arber,Jukka‑Pekka Mecklin,Angel Alonso,Emma R Woodward,D Gareth Evans,Alex Murray,Katie Snape,Ruth E Cleaver,Adam Shaw,Huw J W Thomas,Ajith V Kumar,Dorothy Halliday,Lucy E Side,Rachel E Harrison,Rosemarie Davidson,Ruth Armstrong,Jackie Cook,Rachel Hart,Patrick J Morrison,Julian G Barwell,Alan Donaldson,Zoe Kemp,Jennie Murray,Zosia Miedzybrodzka,Caroline Pottinger,Jonathan Berg,Richard Gallon,D Timothy Bishopon behalf of the CaPP3 co‑investigators The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p760 20 Efficacy and safety of duvakitug in patients with ulcerative colitis (RELIEVE UCCD): a phase 2b, randomised, placebo‑controlled trial Duvakitug治疗溃疡性结肠炎的疗效与安全性（RELIEVE‑UCCD）：2b期随机安慰剂对照试验 Walter Reinisch,David Stepek,Radoslaw Kempinski,Silvio Danese,Bruce E Sands,Bogdan Ratiu‑Duma,Rajendra Singh,Phillip Levine,Hadas Barkay,Nicholas Gross,Ken Abrams,Vipul Jairath The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p775 21 Efficacy and safety of duvakitug in patients with Crohn's disease (RELIEVE UCCD): a phase 2b, randomised, placebo‑controlled trial Duvakitug治疗克罗恩病的疗效与安全性（RELIEVE‑UCCD）：2b期随机安慰剂对照试验 Vipul Jairath,Jaroslaw Kierkuś,George Aaron Duvall,Silvio Danese,Bruce E Sands,Bogdan Ratiu‑Duma,Rajendra Singh,Phillip Levine,Hadas Barkay,Nicholas Gross,Ken Abrams,Walter Reinisch The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p786 22 Efficacy and safety of zalfermin co‑administered with semaglutide in participants with fibrosis and cirrhosis due to metabolic dysfunction‑associated steatohepatitis: a phase 2, dose‑ranging, double‑blind, randomised controlled trial 扎弗明联合司美格鲁肽治疗代谢相关脂肪性肝炎所致肝纤维化与肝硬化受试者的疗效及安全性：2期剂量探索双盲随机对照试验 Rohit Loomba,Jacob George,Laurent Castera,Sven Francque,Eric Lawitz,Ahsan Shoeb,Jesper Ole Clausen,Birgitte Andersen,Anna Bille Larsen,Lise Lotte Gluud The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p797 23 The Rome V criteria for the diagnosis of irritable bowel syndrome in secondary care: a diagnostic accuracy study 二级医疗机构中罗马V标准诊断肠易激综合征的诊断准确度研究 Kyle Staller,Vivek C Goodory,Mais Khasawneh,Christopher J Black,Alexander C Ford The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p812 The Lancet Gastroenterology & Hepatology Commission（《柳叶刀‑胃肠病学和肝病学》专题委员会报告） 24 The role of primary care in response to the global liver disease syndemic: a Lancet Gastroenterology & Hepatology Commission 基层医疗应对全球肝病共病流行的作用——《柳叶刀‑胃肠病学和肝病学》专题委员会报告 Helen Jarvis,Paul N Brennan,Teresa Casanovas,Kelly Casler,Monica Desai,Philip H Evans,John F Dillon,Ignazio Grattagliano,Kate Hallsworth,Vanessa Hebditch,Sema Mandal,Alisa E Pedrana,Jen‑Kuei Peng,Andrew D Schreiner,Abdel‑Aziz Shaheen,Maja Thiele,Patricia C Valery,Julia Verne,Shlomo Vinker,David Whiteley,Martin C S Wong,Shira Zelber‑Sagi The Lancet Gastroenterology & Hepatology. Num 2026, Vol 11(9)：p821

2026-08-26

·靶点AI说

Spyre Therapeutics公布了长效抗TL1A单抗在类风湿关节炎中的Ⅱ期结果，完全占靶，为什么疗效仍不够？SPY072给TL1A赛道划出适应症边界

截至2026年8月26日 2026年8月25日，Spyre Therapeutics公布了长效抗TL1A单抗SPY072在类风湿关节炎中的Ⅱ期结果。两个剂量均达到预期药物浓度，并在整个12周内完整、持续地抑制游离TL1A，安全性也与安慰剂相当。然而，疗效幅度没有达到公司继续优先推进RA单药开发的内部标准。这是一个比简单的“成功”或“失败”更有价值的结果。它没有否定TL1A靶点，却否定了一种过度乐观的行业叙事：只要把TL1A充分阻断，就能在多种自身免疫病中复制IBD的疗效。 SPY072告诉行业，TL1A更像一个高度依赖疾病组织和免疫环境的炎症放大器，而不是适用于所有自身免疫病的主开关。对于已经大量进入TL1A赛道的中国企业而言，下一阶段的竞争重点不再是“有没有一支抗体”，而是能否找到TL1A真正具有疾病决定性的患者、组织和组合机制。一、SPY072究竟取得了什么结果 SKYWAY-RA是一项随机、安慰剂对照的Ⅱ期研究，共纳入143名中重度活动性RA患者。患者既包括未接受过先进疗法的人群，也包括既往治疗经验较多的人群。第12周终点 SPY072高剂量组 SPY072低剂量组安慰剂组结果解读 DAS28-CRP较基线变化 -1.5 -1.9 -1.3 只有低剂量组在主要终点上达到统计学显著。 ACR20 63% 58% 43% 只有高剂量组达到名义统计学显著。 ACR50 31% 38% 19% 只有低剂量组达到名义统计学显著。 ACR70 13% 4% 2% 深度应答人数较少，两个剂量均未形成稳定优势。两个剂量组均达到目标暴露，并完整抑制游离TL1A，但疗效没有呈现一致的剂量依赖关系。治疗组不良事件发生率为27%，安慰剂组为36%；感染相关事件发生率分别为14%和15%。因此，疗效不足很难归因于暴露、耐受性或明显的安全问题。Spyre原始公告这项研究至少给出了三层信息。第一，TL1A在RA中并非完全无效。部分DAS28-CRP、ACR20和ACR50指标相对于安慰剂有所改善，说明TL1A通路确实参与了RA病理过程。第二，TL1A在未经生物标志物筛选的RA患者中可能不是充分的疾病驱动因素。即使游离TL1A被持续压低，TNF、IL-6、JAK信号、B细胞自身抗体、滑膜成纤维细胞和其他致病T细胞网络仍可继续维持疾病。第三，“完全占靶”不能等同于“完全关闭疾病通路”。游离TL1A检测主要回答药物是否实现了药理覆盖，但不能单独证明滑膜组织中的膜型TL1A、DR3阳性细胞和下游网络均已被充分抑制，更不能证明该通路在全部患者中具有同等的重要性。所以，SPY072取得的是RA中的药理学和有限临床概念验证，而不是足以支持商业化单药开发的疗效验证。二、这不是TL1A失败，而是适应症边界被画清了如果只看SPY072的RA结果，很容易得出“TL1A热度过高”的结论。但把IBD数据放在一起，图景就完全不同。默沙东在2026年6月宣布，tulisokibart在Ⅲ期ATLAS-UC诱导研究中达到第12周临床缓解主要终点和关键次要终点。虽然完整数值尚未公开，这是目前首个在UCⅢ期研究中取得阳性结果的抗TL1A单抗。默沙东tulisokibartⅢ期公告 Teva与Sanofi开发的duvakitug也在UC和Crohn病中显示持久疗效。在完成14周诱导并进入长期延伸研究的应答患者中，继续治疗44周后，UC临床缓解率为47%至58%，CD内镜应答率为41%至55%。需要注意，这是经过诱导应答筛选后的维持期人群，不能直接与未经筛选的诱导研究比较，但它仍然支持TL1A阻断在IBD中的持续药效。Duvakitug维持期数据罗氏的afimkibart也已进入UC和CDⅢ期，并继续在RA、特应性皮炎和MASH等疾病中探索。与此同时，Spyre的另一支TL1A单抗SPY002在开放标签UC研究中取得了组织学和临床缓解信号。罗氏2026年研发管线；Spyre SPY002 UC结果这些结果共同说明，TL1A的核心临床价值目前仍集中在黏膜炎症和免疫纤维化。TL1A在RA中的有限疗效不能外推为IBD中的类别失败，同样，IBD中的成功也不能自动外推到所有风湿、皮肤和呼吸疾病。三、为什么TL1A在IBD中可能比RA更重要 TL1A由活化的单核细胞、巨噬细胞、树突细胞和内皮细胞等产生，通过DR3调节效应T细胞、先天淋巴样细胞、Treg及成纤维细胞。它能够放大Th1、Th17等炎症反应，并参与组织重塑和胶原沉积。在IBD中，黏膜屏障破坏、髓系细胞激活、DR3阳性免疫细胞和成纤维细胞程序可以在同一组织空间持续共存。因此，TL1A同时连接了炎症放大和纤维化进展，容易形成相对集中、可被单药打断的病理网络。 RA则更加异质。不同患者可分别由TNF、IL-6、B细胞和自身抗体、T细胞共刺激、JAK信号或滑膜成纤维细胞主导。TL1A虽然可在RA血液、滑液和滑膜中升高，也能促进IL-6和Th17反应，但它可能只是众多并行通路之一。SPY072低、高剂量没有形成稳定的剂量—疗效关系，正符合“通路参与疾病，但不是多数患者的核心瓶颈”这一解释。这也是中国开发者需要接受的现实：一个靶点在疾病组织中升高、与疾病严重度相关，并不等于阻断后一定能获得足够大的治疗效应。相关性只能帮助立项，不能替代干预性临床证据。四、中国TL1A赛道已经从追赶进入拥挤竞争过去三年，TL1A已成为中国自免项目出海最活跃的靶点之一。中国项目分子类型与阶段已公开进展三生国健SSGJ-627 抗TL1A单抗，UCⅡ期 2026年已启动Ⅱ期入组，是国产TL1A单抗的临床领先项目之一。明济生物FG-M701 长效抗TL1A单抗 2024年授权给AbbVie，获得1.5亿美元首付款及近期付款，并有最高15.6亿美元后续里程碑。先声药业SIM0709 TL1A与IL-23p19双抗，交易时处于临床前勃林格殷格翰获得大中华区外权益，潜在里程碑最高约10.58亿欧元。 TrueLab TL-001 长效抗TL1A单抗，Ⅰ期澳大利亚Ⅰ期已完成入组，并与TL-003一起完成大中华区外授权。 TrueLab TL-003 TL1A与IL-23p19双抗，Ⅰ期 2026年在澳大利亚启动Ⅰ期；两项目交易潜在总额为9.85亿美元，并附带Bionyra股权。三生制药718 TL1A与IL-23双抗已进入IND或临床前推进阶段，面向UC和CD。相关信息来自三生制药2026年中期管线更新、AbbVie与明济生物公告、先声药业SIM0709交易公告以及TrueLab与Bionyra交易公告。这些交易证明国际药企仍然高度重视TL1A，但也意味着后来者的门槛迅速升高。2024年前后，一支具有优秀亲和力、长半衰期和良好皮下注射潜力的抗体仍有机会成为高价值资产；到2026年，类似特征已经接近入场券，而不是决定性优势。五、给中国TL1A单抗玩家的五条建议第一，不要因为RA出现有限信号就盲目扩适应症已经进入临床的国产单抗应优先争取UC和CD的人体概念验证。RA可以保留小规模、带生物标志物的探索，但不适合未经筛选地复制大型Ⅱ期研究。PsA和axSpA是否具有更好的TL1A单药机会，还需要等待Spyre在2026年第四季度公布SKYWAY其他亚组结果。第二，亲和力和完全占靶不再等于产品差异化 SPY072本身已经是高效、长效并能持续抑制TL1A的抗体。后来者即使获得更低的体外KD，也未必能带来更高的临床疗效。项目必须同时说明是否覆盖可溶性和膜型TL1A、是否充分阻断TL1A与DR3信号、是否影响TL1A与诱饵受体DcR3的平衡、能否实现高浓度皮下注射，以及维持期是否具备每八至十二周甚至更低频率给药的潜力。第三，把患者分层放在临床开发之前下一代TL1A项目应结合TNFSF15遗传背景、组织TL1A与DR3表达、髓系细胞状态、成纤维细胞和细胞外基质特征，建立复合生物标志物。单独测量血清TL1A通常难以反映病灶组织内的完整通路依赖性。对于RA，未来若继续探索，应优先寻找TL1A高表达且滑膜髓系炎症明显的亚群。对于CD，则应重点分析狭窄、高纤维化风险、既往多线生物药失败及术后复发等表型，而不是把所有中重度患者视为同一种疾病。第四，抗纤维化必须从宣传概念变成临床终点 TL1A在动物模型中具有抗纤维化依据，但中国项目若要建立差异化，需要在临床中纳入磁共振肠道成像、肠壁厚度、狭窄变化、胶原代谢标志物、手术率和长期结构性结局。只观察症状、CRP和短期内镜改善，无法证明药物真正改变了纤维化进程。第五，肠道局部和口服递送仍有模态机会全身长效抗体已经非常拥挤，肠道限制型VHH、口服抗体和炎症环境条件激活分子可能建立新的产品空间。它们有机会降低系统暴露和注射负担，但必须解决蛋白酶稳定性、黏液穿透、病灶组织浓度和持续中和能力。口服形式本身不是优势，能在病灶维持足够药效才是优势。六、TL1A双抗还有机会，但IL-23组合已经不再稀缺 TL1A单抗在IBD中逐步建立疗效后，双抗的目标自然变成突破单药缓解率上限。然而，双抗并不是两个热门靶点的简单相加。第二靶点必须解决TL1A阻断后的残余疾病机制，或者为药物提供组织定位、细胞选择性和给药便利。公开双靶方向主要机会关键风险 2026年判断 TL1A与IL-23p19 两条通路均已有IBD临床验证，有机会同时抑制Th1、Th17、髓系炎症和组织重塑。 SIM0709、TL-003、XmAb412、罗氏p40与TL1A项目及三生718已经形成拥挤竞争。两个可溶性细胞因子组合也未必产生空间协同。已有优质分子者可继续推进；全新跟随型立项优先级下降。 TL1A与α4β7 同时限制致病淋巴细胞进入肠道并抑制局部炎症和纤维化，机制具有互补性。固定双抗是否优于两单抗联合尚未得到临床证明，组织归巢变化也可能影响双臂的空间优势。适合先做联合或共制剂概念验证，再决定是否融合。 TL1A与IL-17A/F 对HS、PsA和axSpA等疾病具有潜在互补性。Spyre正在以SPY072加bimekizumab验证临床增益。目前验证的是联合方案，不是单分子双抗；不同疾病对IL-17的依赖差异很大。值得跟踪，但应等待HS及风湿亚组数据后再扩大布局。 DR3与IL-23R 两个细胞表面受体可能提供共结合和细胞选择性，理论上比双可溶性配体更容易形成空间药理优势。 DR3具有复杂的受体聚簇和潜在激动风险，必须严格进行Fc沉默与残余激动活性筛查。具有下一代潜力，但属于高风险的早期创新。 TL1A与肠道组织地址靶点可以把TL1A阻断集中到病灶组织，改善局部暴露并减少系统作用。地址靶点需要足够组织选择性，且不能因高亲和力产生外周靶点汇或妨碍组织穿透。比单纯再增加一个炎症因子更具长期差异化价值。 TL1A与纤维化执行通路有机会直接覆盖炎症和结构性疾病进展，适合纤维狭窄型CD。第二机制的人体临床验证通常不足，开发周期和终点难度高。科学差异化较高，适合患者组织驱动的探索性项目。其中，TL1A与IL-23p19仍是最容易被资本和跨国药企理解的组合，但已经很难再称为“同类首创”。先声SIM0709、TrueLab TL-003和Xencor XmAb412均已公开布局，罗氏也在推进p40与TL1A双抗RG6730。新的中国项目若只有体外双阻断数据，很难与现有项目拉开距离。Xencor XmAb412公开资料；罗氏研发管线一个值得借鉴的开发思路是先证明联合增益，再决定是否把两支抗体做成一个分子。Spyre的SPY772目前是SPY072与IL-17A/F抗体SPY007的长效共制剂概念。公司先在bimekizumab背景治疗上加入SPY072，直接检验TL1A能否提供额外疗效。这种顺序可以把生物学失败和分子工程失败分开，避免团队在尚未证明组合有效之前，就投入大量资源解决双抗表达、纯化、稳定性和固定剂量比例问题。Spyre SPY772研究设计七、AI应该如何重新设计TL1A项目 AI在TL1A赛道中最不应该做的事情，是根据文献共现频率和靶点热度生成一张“双抗搭子排行榜”。真正有价值的任务，是识别TL1A阻断之后仍然存在的残余疾病网络。首先，应利用患者单细胞转录组和空间组学，确定TL1A来源细胞、DR3阳性应答细胞、成纤维细胞及其他炎症通路是否在同一病灶空间共存。只有空间共存和因果关联同时成立，双抗的局部协同才具有可信基础。其次，应把单抗和联合用药的离体扰动数据纳入模型。模型需要预测的是，在阻断TL1A以后，哪个细胞群和哪条通路仍然保持活性，而不是哪个靶点在未经治疗的患者中表达最高。再次，AI应同时评价疗效和成药性。一个理论上互补的组合，如果导致大分子免疫复合物、明显靶点介导清除、组织穿透下降或固定剂量比例失衡，最终仍可能无法成为药物。最后，临床开发模型需要从“所有IBD患者”转向表型分层。UC、炎症型CD、纤维狭窄型CD、术后复发及多线生物药失败患者的驱动网络并不相同，适合的TL1A产品也可能不同。八、给中国TL1A玩家的最终建议玩家类型建议已进入临床的TL1A单抗继续加速UC和CD临床，以内镜、组织学、长期维持和纤维化数据建立差异化，不宜急于全面扩展RA。仍处于临床前的同质化单抗如果优势仍停留在高亲和力、长半衰期和完全占靶，应重新评估立项价值。已有TL1A与IL-23双抗应尽快证明双抗不劣于两单抗联用，并建立剂量、药代和制剂优势。准备新立项的双抗团队优先寻找能够覆盖残余疾病、提供肠道定位或解决纤维化进展的第二机制，而不是继续复制IL-23组合。具备AI和转化平台的团队应建设患者组织扰动数据库和应答预测模型，把患者分层前移到候选分子确定之前。 SPY072给行业的最终启示不是“TL1A只能用于IBD”，而是TL1A的疗效高度依赖疾病组织、患者亚群和通路层级。TL1A单抗仍可能成为IBD中的重要新类别，但在RA等系统性疾病中，完全占靶并不足以保证足够疗效。对中国企业而言，TL1A赛道的上半场是获得抗体、提高亲和力和延长半衰期；下半场则是患者分层、纤维化终点、肠道定位和真正能够突破单药上限的双机制设计。谁能找到TL1A阻断后的残余疾病驱动，谁才有机会成为这个赛道的下一批赢家。

100 项与 Duvakitug 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D12950	-	-	-

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
溃疡性结肠炎	临床3期	美国	Sanofi	2025-10-08
溃疡性结肠炎	临床3期	中国	Sanofi	2025-10-08
溃疡性结肠炎	临床3期	日本	Sanofi	2025-10-08
溃疡性结肠炎	临床3期	保加利亚	Sanofi	2025-10-08
溃疡性结肠炎	临床3期	加拿大	Sanofi	2025-10-08
溃疡性结肠炎	临床3期	捷克	Sanofi	2025-10-08
溃疡性结肠炎	临床3期	法国	Sanofi	2025-10-08
溃疡性结肠炎	临床3期	德国	Sanofi	2025-10-08
溃疡性结肠炎	临床3期	匈牙利	Sanofi	2025-10-08
溃疡性结肠炎	临床3期	立陶宛	Sanofi	2025-10-08

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05499130 (RELIEVE UCCD, CTgov)	临床2期	克罗恩病 \| 溃疡性结肠炎	290	placebo+TEV-48574 (Placebo (UC))	願窪衊蓋壓獵願構繭觸 = 淵膚鑰製願顧鏇鬱憲範壓齋願製蓋廠壓齋膚築 (簾築遞醖觸製鹹構襯積, 壓積襯襯簾衊廠鏇廠艱 ~ 夢鏇鬱壓簾鬱鬱夢製鏇) 更多	-	2025-12-05
				TEV-48574 (TEV-48574 450 mg (UC))	願窪衊蓋壓獵願構繭觸 = 簾憲獵遞選繭選網醖構壓齋願製蓋廠壓齋膚築 (簾築遞醖觸製鹹構襯積, 觸窪構鑰鏇餘憲積衊繭 ~ 鏇襯襯築壓願艱廠齋鹹) 更多
NCT05499130 (RELIEVE UCCD, NEWS \| Company_Website 1 \| Company_Website 2) 人工标引	临床2期	克罗恩病 \| 溃疡性结肠炎	240	duvakitug (UC + 450 mg)	壓夢衊壓鏇壓鹽餘鏇築(製衊醖網觸夢壓鑰範膚) = 範襯齋鏇構鑰範憲鏇鑰廠鏇願範壓餘襯範壓網 (鹽積窪築鬱製淵觸願繭 ) 达到更多	积极	2024-12-17
				duvakitug (UC + 900 mg)	壓夢衊壓鏇壓鹽餘鏇築(製衊醖網觸夢壓鑰範膚) = 齋繭鏇築壓鹹鑰鹹繭觸廠鏇願範壓餘襯範壓網 (鹽積窪築鬱製淵觸願繭 ) 达到更多
NCT04545385 (CTgov)	临床2期	哮喘	65	Placebo (Placebo)	積淵積觸襯顧鑰齋淵膚 = 繭網艱淵淵襯範鑰鑰願網構壓餘簾積餘願艱齋 (築鏇鏇範蓋築繭齋繭鬱, 壓顧範簾遞鹽窪積鬱餘 ~ 齋醖艱鏇鬱積築糧蓋窪) 更多	-	2023-03-13
				TEV-48574 (TEV-48574)	積淵積觸襯顧鑰齋淵膚 = 顧獵範構範襯鑰鏇衊糧網構壓餘簾積餘願艱齋 (築鏇鏇範蓋築繭齋繭鬱, 膚鬱齋鹹襯醖齋製蓋網 ~ 壓構構廠衊襯遞廠鹹衊) 更多