van Hoeve Karen, Hoffman Ilse, Vermeire Severine
a Department of Pediatric Gastroenterology , University Hospitals Leuven , Leuven , Belgium.
b Department of Gastroenterology & Hepatology , University Hospitals Leuven , Leuven , Belgium.
Expert Opin Drug Saf. 2018 Feb;17(2):185-196. doi: 10.1080/14740338.2018.1413090. Epub 2017 Dec 10.
Although anti-TNF therapy has changed the scenery of pediatric inflammatory bowel diseases (IBD) immensely, there are still patients with an unfortunate outcome. Approximately one third of patients that initially respond to anti-TNF therapy will lose that response over time and need treatment optimization. Loss of response (LOR) is a big concern in IBD management and especially among pediatric patients where treatment options are more limited than in adults. In children it is even more important to sustain response with minimal toxicity. Therapeutic drug monitoring (TDM) is proposed as a tool to reach this goal.
This review focuses on the importance of TDM of anti-TNF and the role TDM has in clinical practice of pediatric IBD.
Although TDM is not yet widely used in pediatric IBD, the available literature suggests it to be a promising tool, especially in patients with LOR to anti-TNF. There is increasing evidence that also in children, higher anti-TNF drug levels are associated with sustained response, and likewise low or undetectable trough levels increase the likelihood of LOR. TDM-based treat to target strategies are being designed in adult studies, but more prospective studies also in pediatric IBD populations looking at the role of proactive testing are needed.
尽管抗TNF治疗极大地改变了儿童炎症性肠病(IBD)的治疗局面,但仍有患者预后不佳。最初对抗TNF治疗有反应的患者中,约三分之一会随着时间推移失去反应,需要优化治疗。反应丧失(LOR)是IBD管理中的一个重大问题,在儿童患者中尤为突出,因为儿童的治疗选择比成人更为有限。在儿童中,以最小的毒性维持反应更为重要。治疗药物监测(TDM)被提议作为实现这一目标的工具。
本综述重点关注抗TNF治疗药物监测的重要性以及TDM在儿童IBD临床实践中的作用。
尽管TDM在儿童IBD中尚未广泛应用,但现有文献表明它是一种有前景的工具,尤其是对于对抗TNF治疗出现LOR的患者。越来越多的证据表明,在儿童中,较高的抗TNF药物水平与持续反应相关,同样,低或无法检测到的谷浓度会增加LOR的可能性。基于TDM的靶向治疗策略正在成人研究中设计,但在儿童IBD人群中也需要更多前瞻性研究来探讨主动检测的作用。