Pub Date : 2025-12-13DOI: 10.1016/s2468-1253(25)00300-0
Jeffrey V Lazarus, Leire Agirre-Garrido, Trenton M White, Anish K Arora, Melina I Manolas, Luis Antonio Diaz, Juan Pablo Arab, Shira Zelber-Sagi, Naim Alkhouri, C Wendy Spearman, Jörn M Schattenberg, Loreta A Kondili, Patrizia Carrieri, Holly F Lofton, Priya Jaisinghani, Sonal Kumar, Ajay Duseja, Mohamed El-Kassas, Hirokazu Takahasi, Debbie L Shawcross, Jonathan G Stine, Marcela Villota-Rivas, Juan Emilio Miralles-Sanchez, Silvana Pannain, Paul N Brennan
{"title":"Best buys for metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis: a global Delphi study","authors":"Jeffrey V Lazarus, Leire Agirre-Garrido, Trenton M White, Anish K Arora, Melina I Manolas, Luis Antonio Diaz, Juan Pablo Arab, Shira Zelber-Sagi, Naim Alkhouri, C Wendy Spearman, Jörn M Schattenberg, Loreta A Kondili, Patrizia Carrieri, Holly F Lofton, Priya Jaisinghani, Sonal Kumar, Ajay Duseja, Mohamed El-Kassas, Hirokazu Takahasi, Debbie L Shawcross, Jonathan G Stine, Marcela Villota-Rivas, Juan Emilio Miralles-Sanchez, Silvana Pannain, Paul N Brennan","doi":"10.1016/s2468-1253(25)00300-0","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00300-0","url":null,"abstract":"","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"143 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145731063","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}
<h3>Background</h3><em>KRAS</em><sup>G12C</sup> mutations are present in around 4% of patients with colorectal cancer and are associated with lower treatment response rates and overall survival. EGFR signalling has been identified as a primary mechanism of resistance to KRAS<sup>G12C</sup> inhibitors. We aimed to evaluate the efficacy and safety of a novel, covalent, small molecule KRAS<sup>G12C</sup> inhibitor, glecirasib (JAB-21822), as monotherapy or in combination with the anti-EGFR cetuximab, in patients with <em>KRAS</em><sup>G12C</sup>-mutated colorectal cancer.<h3>Methods</h3>JAB-21822-1002 was an open-label, non-randomised, dose escalation (phase 1) and expansion (phase 2a) trial evaluating glecirasib monotherapy in <em>KRAS</em><sup>G12C</sup>-mutated solid tumours. JAB-21822-1007 was an open-label, non-randomised, dose escalation (phase 1b) and expansion (phase 2) study evaluating glecirasib plus cetuximab in <em>KRAS</em><sup>G12C</sup>-mutated colorectal, small intestine, and appendiceal cancer. Adult participants (aged ≥18 years) were recruited in China from 17 hospitals for the monotherapy trial and 16 hospitals for the combination trial. Here, we report only on patients with colorectal cancer treated with oral glecirasib at the recommended phase 2 dose (800 mg once daily in 21-day treatment cycles [until disease progression, intolerable toxicity, investigator's discretion, or withdrawal of consent]), pooling phase 1 and 2 data together. In the combination trial, cetuximab was administered intravenously with an initial loading dose of 400 mg/m<sup>2</sup> in the first week, followed by 250 mg/m<sup>2</sup> every week or 500 mg/m<sup>2</sup> every 2 weeks. For this analysis, key eligibility criteria were histologically or cytologically confirmed locally advanced or metastatic colorectal cancer with <em>KRAS</em><sup>G12C</sup> mutation; Eastern Cooperative Oncology Group performance status of 0 or 1; and at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST). For phase 1 of both trials, patients must not have responded to, were not suitable for, or refused standard of care. For phase 2 of both trials, patients must have received at least first-line standard of care and had disease progression or intolerance. Primary endpoints for the monotherapy trial were safety (treatment-emergent adverse events, serious adverse events, treatment-related adverse events, dose-limiting toxicity, and clinically significant changes in vital signs, physical examination, and electrocardiography, and clinically significant unexpected laboratory values of grade ≥3) for phase 1 and objective response rate (complete and partial response) for phase 2a. Primary endpoints for the combination trial were dose-limiting toxicities, maximum tolerated dose, and recommended phase 2 dose for phase 1b and objective response rate for phase 2. The full analysis set was defined as patients with at least one measurable lesion at baseline w
{"title":"Glecirasib with or without cetuximab in previously treated locally advanced or metastatic colorectal cancer with KRASG12C mutation (JAB-21822-1002 and JAB-21822-1007): two open-label, non-randomised phase 1/2 trials","authors":"Jian Li, Zhenghang Wang, Jing Huang, Yi Ba, Baoshan Cao, Suxia Luo, Wenhua Li, Chunmei Bai, Zhengbo Song, Jianping Xiong, Liangjun Zhu, Guangyu An, Yanqiao Zhang, Zhihua Li, Yongsheng Li, Yanhong Gu, Changlu Hu, Xingya Li, Chenghui Huang, Qihan Fu, Lin Shen","doi":"10.1016/s2468-1253(25)00267-5","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00267-5","url":null,"abstract":"<h3>Background</h3><em>KRAS</em><sup>G12C</sup> mutations are present in around 4% of patients with colorectal cancer and are associated with lower treatment response rates and overall survival. EGFR signalling has been identified as a primary mechanism of resistance to KRAS<sup>G12C</sup> inhibitors. We aimed to evaluate the efficacy and safety of a novel, covalent, small molecule KRAS<sup>G12C</sup> inhibitor, glecirasib (JAB-21822), as monotherapy or in combination with the anti-EGFR cetuximab, in patients with <em>KRAS</em><sup>G12C</sup>-mutated colorectal cancer.<h3>Methods</h3>JAB-21822-1002 was an open-label, non-randomised, dose escalation (phase 1) and expansion (phase 2a) trial evaluating glecirasib monotherapy in <em>KRAS</em><sup>G12C</sup>-mutated solid tumours. JAB-21822-1007 was an open-label, non-randomised, dose escalation (phase 1b) and expansion (phase 2) study evaluating glecirasib plus cetuximab in <em>KRAS</em><sup>G12C</sup>-mutated colorectal, small intestine, and appendiceal cancer. Adult participants (aged ≥18 years) were recruited in China from 17 hospitals for the monotherapy trial and 16 hospitals for the combination trial. Here, we report only on patients with colorectal cancer treated with oral glecirasib at the recommended phase 2 dose (800 mg once daily in 21-day treatment cycles [until disease progression, intolerable toxicity, investigator's discretion, or withdrawal of consent]), pooling phase 1 and 2 data together. In the combination trial, cetuximab was administered intravenously with an initial loading dose of 400 mg/m<sup>2</sup> in the first week, followed by 250 mg/m<sup>2</sup> every week or 500 mg/m<sup>2</sup> every 2 weeks. For this analysis, key eligibility criteria were histologically or cytologically confirmed locally advanced or metastatic colorectal cancer with <em>KRAS</em><sup>G12C</sup> mutation; Eastern Cooperative Oncology Group performance status of 0 or 1; and at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST). For phase 1 of both trials, patients must not have responded to, were not suitable for, or refused standard of care. For phase 2 of both trials, patients must have received at least first-line standard of care and had disease progression or intolerance. Primary endpoints for the monotherapy trial were safety (treatment-emergent adverse events, serious adverse events, treatment-related adverse events, dose-limiting toxicity, and clinically significant changes in vital signs, physical examination, and electrocardiography, and clinically significant unexpected laboratory values of grade ≥3) for phase 1 and objective response rate (complete and partial response) for phase 2a. Primary endpoints for the combination trial were dose-limiting toxicities, maximum tolerated dose, and recommended phase 2 dose for phase 1b and objective response rate for phase 2. The full analysis set was defined as patients with at least one measurable lesion at baseline w","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"5 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145657367","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 : 2025-11-27DOI: 10.1016/s2468-1253(25)00268-7
Zheng Wang, Lixing Li, Peiran Huang, Honghu Tu, Xiangyu Zhang, Lei Yu, Fei Liang, Cheng Huang, Shuangjian Qiu, Qinghai Ye, Zhenbin Ding, Xiaowu Huang, Yinghong Shi, Kang Song, Huichuan Sun, Xiaoying Wang, Yongfeng Xu, Yao Yu, Qiang Gao, Lan Zhang, Jian Zhou
<h3>Background</h3>Patients with intrahepatic cholangiocarcinoma have a poor prognosis and high postoperative recurrence rates. Immunochemotherapy has been approved as a first-line treatment for advanced biliary tract cancer. We aimed to explore the activity and safety of camrelizumab, an anti-PD-1 immunotherapy, combined with capecitabine chemotherapy in the adjuvant treatment of patients with resected intrahepatic cholangiocarcinoma.<h3>Methods</h3>ACC was a single-arm, single-centre, open-label, phase 2 trial in adult patients (aged 18–75 years) with R0-resected, pathologically confirmed intrahepatic cholangiocarcinoma (staged as IA with G3 classification or IB–III per the American Joint Committee on Cancer staging system [8th edition, 2017]) done at Zhongshan Hospital, Fudan University (Shanghai, China). Eligible patients had no extrahepatic metastases, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ function. 4–8 weeks after surgery, patients received eight 21-day cycles of intravenous camrelizumab (200 mg on day 1 of each cycle) plus oral capecitabine (1250 mg/m<sup>2</sup> twice daily on days 1–14, followed by a 7-day rest period). The primary endpoint was recurrence-free survival, assessed in the full analysis set (FAS), which included patients who had received at least one dose of either drug. Safety was assessed in the safety set, which included patients who received at least one dose of either drug and completed at least one post-baseline safety assessment following enrolment. This study 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>NCT04295317</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 currently ongoing but no longer recruiting new patients.<h3>Findings</h3>Between Sept 7, 2020, and Nov 18, 2022, 65 patients were enrolled (median age 64 years [IQR 54–70]) and included in the FAS and safety set. 40 (62%) patients were male and 25 (38%) were female. At the data cutoff of Nov 19, 2024, the median follow-up duration was 33·73 months (IQR 24·86–40·38) and 36 (55%) of 65 patients had recurrence (24 [67%] with intrahepatic recurrence only, six [17%] with both intrahepatic and extrahepatic recurrence, and six [17%] with extrahepatic recurrence only). Median recurrence-free survival was 24·29 months (95% CI 13·54–not reached). The most common treatment-related adverse events (occurring in ≥10% of patients) were reactive cutaneous capillary endothelial proliferation (45 [69%] patients), nausea (21 [32%] patients), hand-foot syndrome (19 [29%] patients), pruritus (11 [17%] patients), fatigue (11 [17%] patient
{"title":"Adjuvant camrelizumab combined with capecitabine in patients with intrahepatic cholangiocarcinoma after surgical resection in China (ACC): a single-arm, single-centre, open-label, phase 2 trial","authors":"Zheng Wang, Lixing Li, Peiran Huang, Honghu Tu, Xiangyu Zhang, Lei Yu, Fei Liang, Cheng Huang, Shuangjian Qiu, Qinghai Ye, Zhenbin Ding, Xiaowu Huang, Yinghong Shi, Kang Song, Huichuan Sun, Xiaoying Wang, Yongfeng Xu, Yao Yu, Qiang Gao, Lan Zhang, Jian Zhou","doi":"10.1016/s2468-1253(25)00268-7","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00268-7","url":null,"abstract":"<h3>Background</h3>Patients with intrahepatic cholangiocarcinoma have a poor prognosis and high postoperative recurrence rates. Immunochemotherapy has been approved as a first-line treatment for advanced biliary tract cancer. We aimed to explore the activity and safety of camrelizumab, an anti-PD-1 immunotherapy, combined with capecitabine chemotherapy in the adjuvant treatment of patients with resected intrahepatic cholangiocarcinoma.<h3>Methods</h3>ACC was a single-arm, single-centre, open-label, phase 2 trial in adult patients (aged 18–75 years) with R0-resected, pathologically confirmed intrahepatic cholangiocarcinoma (staged as IA with G3 classification or IB–III per the American Joint Committee on Cancer staging system [8th edition, 2017]) done at Zhongshan Hospital, Fudan University (Shanghai, China). Eligible patients had no extrahepatic metastases, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ function. 4–8 weeks after surgery, patients received eight 21-day cycles of intravenous camrelizumab (200 mg on day 1 of each cycle) plus oral capecitabine (1250 mg/m<sup>2</sup> twice daily on days 1–14, followed by a 7-day rest period). The primary endpoint was recurrence-free survival, assessed in the full analysis set (FAS), which included patients who had received at least one dose of either drug. Safety was assessed in the safety set, which included patients who received at least one dose of either drug and completed at least one post-baseline safety assessment following enrolment. This study 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>NCT04295317</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 currently ongoing but no longer recruiting new patients.<h3>Findings</h3>Between Sept 7, 2020, and Nov 18, 2022, 65 patients were enrolled (median age 64 years [IQR 54–70]) and included in the FAS and safety set. 40 (62%) patients were male and 25 (38%) were female. At the data cutoff of Nov 19, 2024, the median follow-up duration was 33·73 months (IQR 24·86–40·38) and 36 (55%) of 65 patients had recurrence (24 [67%] with intrahepatic recurrence only, six [17%] with both intrahepatic and extrahepatic recurrence, and six [17%] with extrahepatic recurrence only). Median recurrence-free survival was 24·29 months (95% CI 13·54–not reached). The most common treatment-related adverse events (occurring in ≥10% of patients) were reactive cutaneous capillary endothelial proliferation (45 [69%] patients), nausea (21 [32%] patients), hand-foot syndrome (19 [29%] patients), pruritus (11 [17%] patients), fatigue (11 [17%] patient","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"22 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611333","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 : 2025-11-27DOI: 10.1016/s2468-1253(25)00260-2
Wenhao Li, William Alazawi, Rohit Loomba
Globally, metabolic dysfunction-associated steatotic liver disease (MASLD) is now the most common chronic liver disease, affecting up to one in three people in the general population, with an estimated increase in prevalence of more than 50% in the last three decades. The rise in prevalence of MASLD will result in substantial increases in the number patients with decompensated cirrhosis and those developing liver cancer by 2030. Despite the complex pathobiology of MASLD, two major breakthroughs in phase 3 clinical trials now herald an era of licensed therapies for MASLD. The aim of this Review is to summarise these breakthroughs and other developments on the horizon and discuss the key challenges of how to identify the right patients for treatment and how to assess treatment effectiveness in real-world settings.
{"title":"Current and emerging therapeutic landscape for metabolic dysfunction-associated steatohepatitis","authors":"Wenhao Li, William Alazawi, Rohit Loomba","doi":"10.1016/s2468-1253(25)00260-2","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00260-2","url":null,"abstract":"Globally, metabolic dysfunction-associated steatotic liver disease (MASLD) is now the most common chronic liver disease, affecting up to one in three people in the general population, with an estimated increase in prevalence of more than 50% in the last three decades. The rise in prevalence of MASLD will result in substantial increases in the number patients with decompensated cirrhosis and those developing liver cancer by 2030. Despite the complex pathobiology of MASLD, two major breakthroughs in phase 3 clinical trials now herald an era of licensed therapies for MASLD. The aim of this Review is to summarise these breakthroughs and other developments on the horizon and discuss the key challenges of how to identify the right patients for treatment and how to assess treatment effectiveness in real-world settings.","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"115 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145611334","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 : 2025-11-25DOI: 10.1016/s2468-1253(25)00346-2
Mohammad Shebab, Ahmed Al-Hindawi, Shane W Goodwin, Yuhong Yuan, Talat Bessissow, Laurent Peyrin-Biroulet, Vipul Jairath
{"title":"Closing the Middle East and north Africa representation gap in clinical trials in inflammatory bowel disease","authors":"Mohammad Shebab, Ahmed Al-Hindawi, Shane W Goodwin, Yuhong Yuan, Talat Bessissow, Laurent Peyrin-Biroulet, Vipul Jairath","doi":"10.1016/s2468-1253(25)00346-2","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00346-2","url":null,"abstract":"","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"119 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145598884","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 : 2025-11-19DOI: 10.1016/s2468-1253(25)00196-7
Jess L Kaplan, Athos Bousvaros, Dan Turner, Marla Dubinsky, Amy Larkin, Jordan Johns, Yuki Otani, Wallace Crandall, Wendy J Komocsar, Jeffrey S Hyams
<h3>Background</h3>Mirikizumab, a humanised immunoglobulin G4 monoclonal antibody, targets the p19 subunit of IL-23, with demonstrated efficacy and safety in adults with ulcerative colitis and Crohn's disease. This study evaluated the pharmacokinetics, efficacy, and safety of mirikizumab in paediatric participants with moderately-to-severely active ulcerative colitis.<h3>Methods</h3>This 52-week, multicentre, open-label, non-randomised, phase 2 study enrolled paediatric participants (2 to <18 years) with moderately-to-severely active ulcerative colitis with inadequate or loss of response or intolerance to corticosteroids, immunomodulators, biologics, or JAK inhibitors from 19 centres in Canada, Israel, Japan, South Korea, and the USA. Participants received induction doses of intravenous mirikizumab 5 mg/kg or 10 mg/kg (for bodyweight ≤40 kg) or 300 mg (bodyweight >40 kg) at weeks 0, 4, and 8. Clinical response was determined by the modified Mayo score (mMS). Responders at week 12 entered the maintenance period and received subcutaneous doses of mirikizumab 50 mg (bodyweight ≤20 kg), 100 mg (bodyweight >20 to ≤40 kg), or 200 mg (bodyweight >40 kg) every 4 weeks through week 48. Non-responders at week 12 received three additional intravenous induction doses (10 mg/kg [bodyweight ≤40 kg] or 300 mg [bodyweight >40 kg] every 4 weeks), before continuing to subcutaneous maintenance dosing. Here we present the secondary outcomes of safety and efficacy; pharmacokinetics (primary endpoint) data have been reported previously. The modified intention-to-treat and safety populations included participants who received at least one dose of treatment, regardless of adherence to the protocol or treatment. This study 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>NCT04004611</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>26 participants were enrolled between May 18, 2020, and March 15, 2023; mean age was 11·8 years (SD 3·4) and mean weight was 40·5 kg (SD 16·0). 15 (58%) participants were female and 11 (42%) were male. At week 12, 18 (69·2%, 95% CI 50·0–83·5) participants had a clinical response by mMS, ten (38·5%, 95% CI 22·4–57·5) achieved clinical remission by mMS, 14 (53·8%, 95% CI 35·5–71·2) achieved endoscopic remission, four (15·4%, 6·2–33·5) had histologic-endoscopic mucosal improvement (HEMI), one (3·8%, 0·7–18·9) had histologic-endoscopic mucosal remission (HEMR), and 12 (46·2%, 28·8–64·5) achieved symptomatic remission. When assessed by Pediatric Ulcerative Colitis Activity Index (PUCAI), 20 (76·9%, 57·9–89·0) of the 26 participants had
{"title":"Efficacy and safety of mirikizumab in paediatric participants with moderately-to-severely active ulcerative colitis (SHINE-1): a multicentre, open-label, non-randomised phase 2 trial","authors":"Jess L Kaplan, Athos Bousvaros, Dan Turner, Marla Dubinsky, Amy Larkin, Jordan Johns, Yuki Otani, Wallace Crandall, Wendy J Komocsar, Jeffrey S Hyams","doi":"10.1016/s2468-1253(25)00196-7","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00196-7","url":null,"abstract":"<h3>Background</h3>Mirikizumab, a humanised immunoglobulin G4 monoclonal antibody, targets the p19 subunit of IL-23, with demonstrated efficacy and safety in adults with ulcerative colitis and Crohn's disease. This study evaluated the pharmacokinetics, efficacy, and safety of mirikizumab in paediatric participants with moderately-to-severely active ulcerative colitis.<h3>Methods</h3>This 52-week, multicentre, open-label, non-randomised, phase 2 study enrolled paediatric participants (2 to <18 years) with moderately-to-severely active ulcerative colitis with inadequate or loss of response or intolerance to corticosteroids, immunomodulators, biologics, or JAK inhibitors from 19 centres in Canada, Israel, Japan, South Korea, and the USA. Participants received induction doses of intravenous mirikizumab 5 mg/kg or 10 mg/kg (for bodyweight ≤40 kg) or 300 mg (bodyweight >40 kg) at weeks 0, 4, and 8. Clinical response was determined by the modified Mayo score (mMS). Responders at week 12 entered the maintenance period and received subcutaneous doses of mirikizumab 50 mg (bodyweight ≤20 kg), 100 mg (bodyweight >20 to ≤40 kg), or 200 mg (bodyweight >40 kg) every 4 weeks through week 48. Non-responders at week 12 received three additional intravenous induction doses (10 mg/kg [bodyweight ≤40 kg] or 300 mg [bodyweight >40 kg] every 4 weeks), before continuing to subcutaneous maintenance dosing. Here we present the secondary outcomes of safety and efficacy; pharmacokinetics (primary endpoint) data have been reported previously. The modified intention-to-treat and safety populations included participants who received at least one dose of treatment, regardless of adherence to the protocol or treatment. This study 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>NCT04004611</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>26 participants were enrolled between May 18, 2020, and March 15, 2023; mean age was 11·8 years (SD 3·4) and mean weight was 40·5 kg (SD 16·0). 15 (58%) participants were female and 11 (42%) were male. At week 12, 18 (69·2%, 95% CI 50·0–83·5) participants had a clinical response by mMS, ten (38·5%, 95% CI 22·4–57·5) achieved clinical remission by mMS, 14 (53·8%, 95% CI 35·5–71·2) achieved endoscopic remission, four (15·4%, 6·2–33·5) had histologic-endoscopic mucosal improvement (HEMI), one (3·8%, 0·7–18·9) had histologic-endoscopic mucosal remission (HEMR), and 12 (46·2%, 28·8–64·5) achieved symptomatic remission. When assessed by Pediatric Ulcerative Colitis Activity Index (PUCAI), 20 (76·9%, 57·9–89·0) of the 26 participants had ","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"4 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145546241","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 : 2025-11-19DOI: 10.1016/s2468-1253(25)00234-1
Stephanie A Vuijk, Esmée H Boute, Lissy de Ridder
No Abstract
没有抽象的
{"title":"Expanding the therapeutic arsenal for paediatric ulcerative colitis","authors":"Stephanie A Vuijk, Esmée H Boute, Lissy de Ridder","doi":"10.1016/s2468-1253(25)00234-1","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00234-1","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"145 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145546238","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 : 2025-11-17DOI: 10.1016/s2468-1253(25)00320-6
Vidhi Singh, Jayraan Badiee, Alexander Goldowsky, David Russo, Folasade P May
No Abstract
没有抽象的
{"title":"Colorectal cancer screening in LGBTQIA+ people: an urgent call for equity","authors":"Vidhi Singh, Jayraan Badiee, Alexander Goldowsky, David Russo, Folasade P May","doi":"10.1016/s2468-1253(25)00320-6","DOIUrl":"https://doi.org/10.1016/s2468-1253(25)00320-6","url":null,"abstract":"No Abstract","PeriodicalId":56028,"journal":{"name":"Lancet Gastroenterology & Hepatology","volume":"6 1","pages":""},"PeriodicalIF":35.7,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145536427","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}
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