Precision Medicine in Crohn's Disease and Ulcerative Colitis: Predicting Disease Flare and Disease progression

克罗恩病和溃疡性结肠炎的精准医学：预测疾病发作和疾病进展

• 批准号: 2259645
• 金额: --
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2259645
• 关键词: Precision; Medicine; Crohn; Disease; Ulcerative

Crohn's disease and ulcerative colitis are the common forms of inflammatory bowel disease affecting up to 1 in 100 people in the UK. Incidence rates are increasing sharply in the previously undeveloped world, driven by urbanisation and adoption of a Western lifestyle. IBD typically manifests in adolescence / early adulthood with disturbed bowel function, a robust inflammatory response, systemic upset, psycho-social disturbance and substantial health-economic burden. Recent years have seen massive biotech / pharma investment in IBD with multiple different drug modalities now approved for use. However, remission rates are hitting a ceiling at 1 year of 30-40%, and no reliable biomarkers exist to aid with drug positioning. Management of IBD is further complicated by our inability to prognosticate on treatment response, disease flare or disease progression. The PREdiCCt study www.predicct.co.uk, led by Dr Charlie Lees, is presently recruiting 3100 people with IBD from across the UK. Patients are recruited in clinical remission, and followed-up during two years. Detailed baseline data is collected for all patients. Among others, this includes electronic health records held by NHS, whole-genome and metabolomic sequencing, diet/lifestyle data recorded through a mobile app as well as a full blood panel. Throughout the follow-up, the mobile app is also used to regularly collect patient self-reported disease outcomes. The overarching goal of this project is to develop and apply computational strategies which can improve the stratification and subsequent treatment of IBD patients. High-dimensional Bayesian hierarchical models will be used as a natural and powerful framework to combine information from multiple data sources, whist appropriately quantifying statistical uncertainty. In particular, we seek to address the following research questions: 1. What aspects of disease phenotype, diet, lifestyle, genetics and the gut microbiota contribute to a) disease flare, b) disease progression & c) treatment response in IBD? 2. How can we stratify patients based on disease biology and risk of progression? 3. Based on this, how can we intervene to improve patient outcomes?

克罗恩病和溃疡性结肠炎是炎症性肠病的常见形式，在英国影响多达十分之一的人。在城市化和西方生活方式的推动下，以前不发达国家的发病率急剧上升。 IBD 通常出现在青春期/成年早期，伴有肠道功能紊乱、强烈的炎症反应、全身不适、社会心理障碍和沉重的健康经济负担。近年来，IBD 领域出现了大量生物技术/制药投资，多种不同的药物模式现已获批使用。然而，缓解率已达到 1 年 30-40% 的上限，并且不存在可靠的生物标志物来帮助药物定位。由于我们无法预测治疗反应、疾病发作或疾病进展，IBD 的管理变得更加复杂。由 Charlie Lees 博士领导的 PREdiCCt 研究 www.predicct.co.uk 目前正在英国各地招募 3100 名 IBD 患者。招募临床缓解期的患者，并进行两年的随访。收集所有患者的详细基线数据。其中包括 NHS 持有的电子健康记录、全基因组和代谢组测序、通过移动应用程序记录的饮食/生活方式数据以及全血检测。在整个随访过程中，移动应用程序还用于定期收集患者自我报告的疾病结果。该项目的总体目标是开发和应用计算策略，以改善 IBD 患者的分层和后续治疗。高维贝叶斯分层模型将被用作一个自然且强大的框架来组合来自多个数据源的信息，同时适当地量化统计不确定性。我们特别寻求解决以下研究问题： 1. 疾病表型、饮食、生活方式、遗传学和肠道微生物群的哪些方面有助于 IBD 的 a) 疾病发作、b) 疾病进展和 c) 治疗反应？ 2. 我们如何根据疾病生物学和进展风险对患者进行分层？ 3. 基于此，我们如何进行干预以改善患者的治疗效果？

项目成果

Patterns of emergency admission for IBD patients over the last 10 years in Lothian, Scotland: a retrospective prevalent cohort analysis.

• DOI: 10.1111/apt.16867
• 发表时间: 2022-07
• 期刊: ALIMENTARY PHARMACOLOGY & THERAPEUTICS
• 影响因子: 7.6
• 作者: Lyons, Mathew;Derikx, Lauranne A. A. P.;Fulforth, James;McCall, Sophie;Plevris, Nikolas;Jenkinson, Philip W.;Kirkwood, Kathryn;Siakavellas, Spyros;Lucaciu, Laura;Constantine-Cooke, Nathan;Arnott, Ian D.;Henderson, Paul;Russell, Richard K.;Wilson, David C.;Lees, Charlie W.;Jones, Gareth-Rhys
• 通讯作者: Jones, Gareth-Rhys

Longitudinal Faecal Calprotectin Profiles Characterise Disease Course Heterogeneity in Crohn's Disease

纵向粪便钙卫蛋白谱表征克罗恩病的病程异质性

• DOI: 10.1101/2022.08.16.22278320
• 发表时间: 2022
• 作者: Constantine-Cooke N

Real-world experience with tofacitinib in ulcerative colitis: a systematic review and meta-analysis.

• DOI: 10.1177/17562848211064004
• 发表时间: 2021
• 期刊: Therapeutic advances in gastroenterology
• 影响因子: 4.2
• 作者: Lucaciu LA;Constantine-Cooke N;Plevris N;Siakavellas S;Derikx LAAP;Jones GR;Lees CW
• 通讯作者: Lees CW

Effectiveness and Safety of Adalimumab Biosimilar SB5 in Inflammatory Bowel Disease: Outcomes in Originator to SB5 Switch, Double Biosimilar Switch and Bio-Naïve SB5 Observational Cohorts.

Adalimumab生物仿制药SB5在炎症性肠病中的有效性和安全性：发起人到SB5开关的结局，双生物仿制药开关和不使用生物的SB5观察群。

• DOI: 10.1093/ecco-jcc/jjab100
• 发表时间: 2021-12-18
• 期刊: Journal of Crohn's & colitis
• 作者: Derikx LAAP;Dolby HW;Plevris N;Lucaciu L;Rees CS;Lyons M;Siakavellas SI;Constantine-Cooke N;Jenkinson P;Su S;O'Hare C;Kirckpatrick L;Merchant LM;Noble C;Arnott ID;Jones GR;Lees CW
• 通讯作者: Lees CW