Honap Sailish, Agrinier Nelly, Torres Joana, Croitoru Kenneth, Lee Sun-Ho, Turpin Williams, Ungaro Ryan C, Agrawal Manasi, Peter Inga, Turner Dan, Dotan Iris, Hart Ailsa L, Netter Patrick, D'Haens Geert, Rubin David T, Ng Siew C, Gearry Richard, Jairath Vipul, Ananthakrishnan Ashwin N, Danese Silvio, Colombel Jean-Frederic, Peyrin-Biroulet Laurent
School of Immunology and Microbial Sciences, King's College London, London, UK; Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK.
CHRU-Nancy, CIC, Epidémiologie Clinique and Inserm, INSPIIRE, Université de Lorraine, Nancy, France.
Lancet Gastroenterol Hepatol. 2025 Jun;10(6):593-604. doi: 10.1016/S2468-1253(24)00439-4. Epub 2025 Apr 2.
Therapeutic progress in inflammatory bowel disease (IBD) has hitherto focused on reducing inflammation to minimise long-term complications. However, strategies aimed at preventing IBD and attenuating its disease course are particularly appealing. This concept is derived from accumulating evidence for an "at-risk" preclinical state and the associations linking genetic background and numerous environmental exposures to disease pathogenesis. Trials in rheumatoid arthritis and type 1 diabetes have identified interventions to delay disease onset, modify the subsequent disease course (potentially protecting against irreversible tissue and end organ damage), and prolong normal quality of life. Prevention and interception trials have major challenges compared with therapeutic trials across a number of domains, including ethical considerations, eligibility criteria, sample size, and optimal endpoints. This Review investigates important factors in designing high-quality prevention trials and evaluates the feasibility and current progress of such trials in IBD, aiming to identify therapeutic strategies for populations at risk.
迄今为止,炎症性肠病(IBD)的治疗进展主要集中在减轻炎症以尽量减少长期并发症。然而,旨在预防IBD并减缓其病程的策略尤其具有吸引力。这一概念源于越来越多关于“风险”临床前状态的证据,以及将遗传背景和多种环境暴露与疾病发病机制联系起来的关联。类风湿性关节炎和1型糖尿病的试验已经确定了一些干预措施,可延缓疾病发作、改变随后的病程(可能防止不可逆的组织和终末器官损伤)并延长正常生活质量。与治疗性试验相比,预防和干预试验在多个领域面临重大挑战,包括伦理考量、入选标准、样本量和最佳终点。本综述研究了设计高质量预防试验的重要因素,并评估了此类试验在IBD中的可行性和当前进展,旨在为高危人群确定治疗策略。