Optimising carotegrast methyl use in ulcerative colitis: patient profiling, predictive biomarkers, and timing of efficacy evaluation (ASPECT study).

IF 5.5 2区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Katsuyoshi Matsuoka, Fumihito Hirai, Kenji Watanabe, Ryota Hokari, Taku Kobayashi, Masayuki Saruta, Hiroshi Nakase, Takahiro Suzuki, Gakuto Yamazaki, Toshifumi Hibi, Mamoru Watanabe, Tadakazu Hisamatsu
{"title":"Optimising carotegrast methyl use in ulcerative colitis: patient profiling, predictive biomarkers, and timing of efficacy evaluation (ASPECT study).","authors":"Katsuyoshi Matsuoka, Fumihito Hirai, Kenji Watanabe, Ryota Hokari, Taku Kobayashi, Masayuki Saruta, Hiroshi Nakase, Takahiro Suzuki, Gakuto Yamazaki, Toshifumi Hibi, Mamoru Watanabe, Tadakazu Hisamatsu","doi":"10.1007/s00535-025-02299-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Carotegrast methyl is approved for treating patients with moderately active ulcerative colitis with inadequate response to 5-aminosalicylic acid agents. However, real-world evidence to guide optimal use is limited. This retrospective study aimed to characterise suitable patient profiles, identify biomarkers predictive of carotegrast methyl efficacy, and determine the appropriate timing for treatment evaluation.</p><p><strong>Methods: </strong>We analysed data from 186 patients enrolled in a phase 3 trial of carotegrast methyl (96 carotegrast methyl, 90 placebo). We assessed biomarkers (leucine-rich α-2 glycoprotein, C-reactive protein, faecal calprotectin, and anti-integrin αvβ6 antibody titres) alongside clinical outcomes and assessed symptom diaries and maintenance therapies.</p><p><strong>Results: </strong>Low disease activity at baseline (partial Mayo score ≤ 5) was associated with higher remission rates (56.1 vs. 33.3%). Anti-integrin αvβ6 antibody titres of < 44.6 U/mL at baseline predicted higher clinical remission rates (49.1 vs. 26.8%). Symptom improvement was detectable from week 2. Faecal calprotectin correlated with the endoscopic subscore at the end of treatment (ρ = 0.566); a faecal calprotectin level of < 387.5 µg/g predicted Mayo endoscopic subscore 0/1. Most patients maintained remission with oral 5-aminosalicylic acid alone; the 1-year maintenance rate was 56.5%.</p><p><strong>Conclusions: </strong>Carotegrast methyl appears most effective in patients with moderately active ulcerative colitis with low disease activity, with week 2 and beyond as an appropriate time point for assessing efficacy. Anti-integrin αvβ6 antibody titre shows promise in predicting response to carotegrast methyl. Faecal calprotectin may serve as a non-invasive surrogate for evaluating endoscopic healing.</p>","PeriodicalId":16059,"journal":{"name":"Journal of Gastroenterology","volume":" ","pages":""},"PeriodicalIF":5.5000,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Gastroenterology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00535-025-02299-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Carotegrast methyl is approved for treating patients with moderately active ulcerative colitis with inadequate response to 5-aminosalicylic acid agents. However, real-world evidence to guide optimal use is limited. This retrospective study aimed to characterise suitable patient profiles, identify biomarkers predictive of carotegrast methyl efficacy, and determine the appropriate timing for treatment evaluation.

Methods: We analysed data from 186 patients enrolled in a phase 3 trial of carotegrast methyl (96 carotegrast methyl, 90 placebo). We assessed biomarkers (leucine-rich α-2 glycoprotein, C-reactive protein, faecal calprotectin, and anti-integrin αvβ6 antibody titres) alongside clinical outcomes and assessed symptom diaries and maintenance therapies.

Results: Low disease activity at baseline (partial Mayo score ≤ 5) was associated with higher remission rates (56.1 vs. 33.3%). Anti-integrin αvβ6 antibody titres of < 44.6 U/mL at baseline predicted higher clinical remission rates (49.1 vs. 26.8%). Symptom improvement was detectable from week 2. Faecal calprotectin correlated with the endoscopic subscore at the end of treatment (ρ = 0.566); a faecal calprotectin level of < 387.5 µg/g predicted Mayo endoscopic subscore 0/1. Most patients maintained remission with oral 5-aminosalicylic acid alone; the 1-year maintenance rate was 56.5%.

Conclusions: Carotegrast methyl appears most effective in patients with moderately active ulcerative colitis with low disease activity, with week 2 and beyond as an appropriate time point for assessing efficacy. Anti-integrin αvβ6 antibody titre shows promise in predicting response to carotegrast methyl. Faecal calprotectin may serve as a non-invasive surrogate for evaluating endoscopic healing.

优化甲基胡萝卜素在溃疡性结肠炎中的应用:患者分析、预测性生物标志物和疗效评估时间(ASPECT研究)。
背景:甲基胡萝卜素被批准用于治疗对5-氨基水杨酸药物反应不足的中度活动性溃疡性结肠炎患者。然而,指导最佳使用的实际证据是有限的。这项回顾性研究旨在描述合适的患者概况,确定预测甲基胡萝卜素组疗效的生物标志物,并确定适当的治疗评估时间。方法:我们分析了参加甲基胡萝卜素组3期试验的186例患者的数据(甲基胡萝卜素组96例,安慰剂90例)。我们评估了生物标志物(富含亮氨酸的α-2糖蛋白、c反应蛋白、粪便钙保护蛋白和抗整合素αvβ6抗体滴度)以及临床结果,并评估了症状日记和维持疗法。结果:基线时疾病活动度低(部分Mayo评分≤5)与较高的缓解率相关(56.1 vs 33.3%)。结论:甲基胡萝卜素在疾病活动度低的中度活动性溃疡性结肠炎患者中最有效,以第2周及以上为评估疗效的合适时间点。抗整合素αvβ6抗体滴度在预测对胡萝卜素甲酯的反应方面有希望。粪钙保护蛋白可作为评估内镜下愈合的非侵入性替代物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Journal of Gastroenterology
Journal of Gastroenterology 医学-胃肠肝病学
CiteScore
12.20
自引率
1.60%
发文量
99
审稿时长
4-8 weeks
期刊介绍: The Journal of Gastroenterology, which is the official publication of the Japanese Society of Gastroenterology, publishes Original Articles (Alimentary Tract/Liver, Pancreas, and Biliary Tract), Review Articles, Letters to the Editors and other articles on all aspects of the field of gastroenterology. Significant contributions relating to basic research, theory, and practice are welcomed. These publications are designed to disseminate knowledge in this field to a worldwide audience, and accordingly, its editorial board has an international membership.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信