Robarts Clinical Trials, Inc., London, ON, Canada.
Division of Gastroenterology, Department of Medicine, School of Medicine, IBD Center, University of California San Diego, 9500 Gilman Drive #0956, La Jolla, CA, 92093, USA.
BioDrugs. 2019 Oct;33(5):453-468. doi: 10.1007/s40259-019-00366-1.
Monoclonal antibody (mAb) therapies have revolutionized the treatment of several chronic inflammatory diseases, including the inflammatory bowel diseases (IBD), Crohn's disease, and ulcerative colitis. While efficacious, responses to these therapies vary considerably from patient to patient, due in part to inter- and intra-individual variability in pharmacokinetics (PK) and drug exposure. The concept of personalized medicine to monitor drug exposure and to adjust dosing in individual patients is consequently gaining acceptance as a powerful tool to optimize mAb therapy for improved outcomes in IBD. This review provides a brief overview of the different mAbs currently approved or in development for the treatment of IBD, including their presumed mechanisms of action and PK properties. Specifically described are (1) the factors known to affect mAb PK and drug exposure in patients with IBD, (2) the value of population PK/pharmacodynamic (PD) modeling to identify and understand the influence of these factors on drug exposure and effect, and (3) the clinical evidence for the potential of therapeutic drug monitoring (TDM) to improve IBD outcomes in response to mAb-based therapy. Incorporation of PK/PD parameters into clinical decision support tools has the potential to guide therapeutic decision making and aid implementation of personalized medicine strategies in patients with IBD.
单克隆抗体 (mAb) 疗法已经彻底改变了几种慢性炎症性疾病的治疗方法，包括炎症性肠病（IBD）、克罗恩病和溃疡性结肠炎。虽然这些疗法有效，但由于药代动力学（PK）和药物暴露在个体间和个体内存在差异，患者对这些疗法的反应差异很大。因此，监测药物暴露并根据个体患者调整剂量的个性化医学概念作为一种优化 mAb 治疗以改善 IBD 结果的有力工具，正在逐渐被接受。这篇综述简要概述了目前批准或正在开发用于治疗 IBD 的不同 mAb，包括它们的作用机制和 PK 特性。具体描述了 (1) 已知影响 IBD 患者 mAb PK 和药物暴露的因素，(2) 群体 PK/药效动力学 (PD) 建模在识别和理解这些因素对药物暴露和效果的影响方面的价值，以及 (3) 治疗药物监测 (TDM) 改善对 mAb 治疗反应的 IBD 结局的临床证据。将 PK/PD 参数纳入临床决策支持工具中，有可能指导治疗决策，并帮助实施 IBD 患者的个性化医学策略。
