Papamichael Konstantinos, Cheifetz Adam S
Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Expert Opin Drug Metab Toxicol. 2021 Dec;17(12):1423-1431. doi: 10.1080/17425255.2021.2027367. Epub 2022 Jan 11.
Therapeutic drug monitoring (TDM) is useful for optimizing monoclonal antibodies (mAbs) for the treatment of immune-mediated inflammatory disorders including inflammatory bowel disease (IBD). However, TDM in clinical practice is still restricted by long turnaround times between sampling and results and the fact that dosing of mAbs to a target drug concentration is challenging due to high pharmacokinetic (PK) variability at both a population and patient level. Overcoming these barriers may be addressed by point-of-care (POC) assays, model-informed precision dosing (MIPD), and pharmacogenetics/pharmacogenomics.
This review provides an overview of the optimization of TDM of mAbs in IBD including POC testing, MIPD, and pharmacogenetics.
Recent advances in sampling, quantification, and support of clinical decisions include POC assays and PK dashboards, which may allow for prompt and precise application of TDM in clinical practice. Future perspectives toward a more personalized implementation of TDM could include the incorporation of pharmacogenetics/pharmacogenomics to identify subgroups of patients who would benefit more from proactive TDM or combination therapy such as those prone to immunogenicity and/or accelerated drug clearance. However, there are still challenges regarding the implementation of these innovative approaches, and more data from prospective studies and randomized controlled trials are needed.
治疗药物监测(TDM)有助于优化单克隆抗体(mAb),用于治疗包括炎症性肠病(IBD)在内的免疫介导的炎症性疾病。然而,临床实践中的TDM仍受到采样与结果之间周转时间长的限制,并且由于在群体和患者层面都存在较高的药代动力学(PK)变异性,将mAb剂量调整至目标药物浓度具有挑战性。即时检测(POC)、模型引导的精准给药(MIPD)以及药物遗传学/药物基因组学或许可以克服这些障碍。
本综述概述了IBD中mAb的TDM优化,包括POC检测、MIPD和药物遗传学。
采样、定量以及临床决策支持方面的最新进展包括POC检测和PK仪表盘,这可能使TDM在临床实践中得以迅速且精准地应用。TDM更加个性化实施的未来展望可能包括纳入药物遗传学/药物基因组学,以识别那些从主动TDM或联合治疗中获益更多的患者亚组,例如那些易于产生免疫原性和/或药物清除加速的患者。然而,这些创新方法的实施仍存在挑战,需要更多来自前瞻性研究和随机对照试验的数据。