Gastroenterology Department, Sheba Medical Center, Affiliated to Tel-Aviv University, Tel-Aviv, Israel.
Gastroenterology Department, Sheba Medical Center, Affiliated to Tel-Aviv University, Tel-Aviv, Israel.
Curr Opin Pharmacol. 2020 Dec;55:132-140. doi: 10.1016/j.coph.2020.10.011. Epub 2020 Nov 26.
Despite the evolving therapeutic armamentarium, the treatment of IBD patients remains challenging and many patients fail to respond to biologic agents. With the limited yield of clinical factors to predict the outcome of biologic treatments, studies have focused on identifying genetic alterations and circulating or tissue biomarkers to identify patients who are likely to respond to therapy. In this review, we examine the current knowledge and status of genetic, expression biomarkers, and microbiome predictors. The search for genetic predictors has yielded many genetic loci variants, but few were reproducible. Expression studies of putative biomarkers show promising results, especially with TREM1, oncostatin M and TNF biomarkers, but confirmatory studies are warranted. Finally, the microbiome is emerging as an important player with specific taxa and functional pathways differentially abundant and enriched in responders versus non-responders to certain biologics. Integrating different factors into a robust predictive model, which is both reproducible, accurate and affordable, remains the main challenge before these individualized strategies can reach clinical use.
尽管治疗方法不断发展，但 IBD 患者的治疗仍然具有挑战性，许多患者对生物制剂没有反应。由于临床因素预测生物治疗效果的效果有限，因此研究集中在确定遗传改变和循环或组织生物标志物，以识别可能对治疗有反应的患者。在这篇综述中，我们检查了遗传、表达生物标志物和微生物组预测因子的现有知识和现状。对遗传预测因子的研究产生了许多遗传位点变异，但很少具有可重复性。有前途的生物标志物表达研究，特别是 TREM1、oncostatin M 和 TNF 生物标志物，但需要进行确认性研究。最后，微生物组作为一个重要的参与者出现，特定的分类群和功能途径在对某些生物制剂有反应和无反应的患者中存在差异。在这些个体化策略能够临床应用之前，将不同的因素整合到一个可靠的、可重复、准确和负担得起的预测模型中仍然是主要挑战。
