炎症性肠病生物制剂治疗药物监测

W. Afif, Arti Wongcha-um
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引用次数: 0

摘要

生物制剂已经彻底改变了溃疡性结肠炎(UC)和克罗恩病(CD)的炎症性肠病(IBD)患者的治疗。有几类生物制剂用于治疗IBD,包括针对TNF、整合素、il - 12/23和IL-23单克隆抗体的单克隆抗体。尽管抗肿瘤坏死因子药物有效,但大约30%的患者是原发性无反应(PNR),另外50%的患者随着时间的推移失去反应(继发性反应丧失[SLR])。治疗药物监测(TDM)通过测量药物谷浓度和抗药物抗体(ADA)提供了生物剂量优化的工具。药物浓度与治疗效果呈正相关,但如何、何时以及为谁进行TDM仍存在问题。成功的实施受到几个因素的挑战,如最佳药物靶点的变化、不同类型的药物检测分析、个体药代动力学和疾病严重程度。近年来,各个专家组提供了抗tnf治疗的反应性TDM指南;然而,关于主动TDM和反应性TDM在非抗tnf生物制剂中的作用,仍然存在知识差距。发表在《美国胃肠病学杂志》(AJG)上的最新和全面的专家共识声明,试图通过提倡将反应性TDM用于抗tnf药物以及在某些情况下使用主动TDM来填补这一空白。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Therapeutic drug monitoring of biologics in inflammatory bowel disease
Biologics have revolutionized the management of patients with inflammatory bowel disease (IBD), in both ulcerative colitis (UC) and Crohn’s disease (CD). There are several classes of biologics used to treat IBD, including monoclonal antibodies directed against TNF, integrin, IL12/23, and IL-23 monoclonal antibodies. Despite the effectiveness of anti-TNF medications, approximately 30% of patients are primary non-responders (PNR), and another 50% lose response over time (secondary loss of response [SLR]). Therapeutic drug monitoring (TDM) provides a tool for biologic dose optimization by measuring drug trough concentrations and anti-drug antibodies (ADA). Drug concentrations are positively correlated to therapeutic benefits, but questions remain on how, when and for whom to perform TDM. Successful implementation is challenged by several factors such as variations in optimal drug targets, different types of drug detection assays, individual pharmacokinetics, and disease severity. Over recent years, various expert groups have provided guidelines on reactive TDM of anti-TNF therapies; however, a knowledge gap still exists on the role of proactive TDM, as well as reactive TDM for non-anti-TNF biologics. The most recent and comprehensive expert consensus statement published in the American Journal of Gastroenterology (AJG), attempted to fill this gap by advocating for the use of reactive TDM for anti-TNF medications, as well as for proactive TDM in certain scenarios.
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