Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
Robarts Clinical Trials Inc, London, ON, Canada.
Aliment Pharmacol Ther. 2018 Dec;48(11-12):1213-1231. doi: 10.1111/apt.15033. Epub 2018 Oct 30.
Inflammatory bowel disease (IBD) is characterised by substantial heterogeneity in treatment response. With an expanding number of therapeutic agents, identifying optimal treatment at the patient level remains a major challenge.
To systematically review the available literature on predictive biomarkers of therapeutic response in IBD.
An electronic literature search was performed on 30 January 2018 using MEDLINE, EMBASE and the Cochrane Library. Retrospective, prospective, uncontrolled and controlled studies reporting on biomarkers predicting therapeutic response in paediatric and adult IBD populations were eligible for inclusion. The methodological quality of the included studies was assessed using the QUIPS tool. Due to anticipated heterogeneity and limited data, a qualitative, rather than quantitative, assessment was planned.
Of the 10 638 citations identified, 92 articles met the inclusion criteria. Several potential DNA, mRNA and protein markers were evaluated as predictive biomarkers. Most studies focused on predicting response to anti-TNF agents. Substantial between-study heterogeneity was identified with respect to both the biomarkers studied and the definition of response. None of the included studies received a low risk of bias rating for all six domains. Currently, none of the biomarkers is sufficiently predictive for clinical use.
The search for predictive biomarkers is still in its infancy and current evidence is limited. Future research efforts should take into account the high patient heterogeneity within prospective trials with objective response assessment. Predictive models will most likely comprise a combination of several molecular markers from integrated omics-levels and clinical characteristics.
炎症性肠病(IBD)的治疗反应存在很大的异质性。随着治疗药物的不断增加,如何在患者层面确定最佳治疗方案仍然是一个主要的挑战。
系统综述 IBD 治疗反应预测生物标志物的现有文献。
于 2018 年 1 月 30 日检索 MEDLINE、EMBASE 和 Cochrane 图书馆,纳入报道预测儿童和成人 IBD 患者治疗反应的生物标志物的回顾性、前瞻性、非对照和对照研究。采用 QUIPS 工具评估纳入研究的方法学质量。由于预期存在异质性和数据有限,计划进行定性而非定量评估。
在 10638 条引文中共纳入 92 篇文章。评估了多种潜在的 DNA、mRNA 和蛋白质标志物作为预测生物标志物。大多数研究集中于预测对 TNF 拮抗剂的反应。在研究的生物标志物和反应定义方面均存在显著的研究间异质性。纳入的研究均未在所有 6 个领域获得低偏倚风险评分。目前,尚无任何生物标志物具有足够的预测临床应用价值。
对预测生物标志物的研究仍处于起步阶段,目前的证据有限。未来的研究应考虑前瞻性试验中存在的高患者异质性,并进行客观反应评估。预测模型可能最有可能由整合的组学水平和临床特征的几个分子标志物组合而成。