Academic Medical Center Division of Gastroenterology, Amsterdam, Netherlands.
Therapeutic Biologics Program, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation Research, Food and Drug Administration, Silver Spring, Maryland, USA.
AAPS J. 2018 Sep 5;20(6):99. doi: 10.1208/s12248-018-0257-y.
The introduction of monoclonal antibodies (mAbs) to the treatment of inflammatory bowel disease (IBD) was an important medical milestone. MAbs have been demonstrated as safe and efficacious treatments of IBD. However, a large percentage of patients either fail to respond initially or lose response to therapy after a period of treatment. Although there are factors associated with poor treatment outcomes in IBD, one cause for treatment failure may be low mAb exposure. Consequently, gastroenterologists have begun using therapeutic drug monitoring (TDM) to guide dose adjustment. However, while beneficial, TDM does not provide sufficient information to effectively adjust doses. The pharmacokinetics (PK) and pharmacodynamics (PD) of mAbs are complex, with numerous factors impacting on mAb PK and PD. The concept of dashboard-guided dosing based on Bayesian PK models allows physicians to combine TDM with factors influencing mAb PK to individualize therapy more effectively. One issue with TDM has been the slow turnaround of assay results, either necessitating an additional clinic visit for a sample or reacting to TDM results at a subsequent, rather than the current, dose. New point-of-care (POC) assays for mAbs are being developed that would potentially allow physicians to determine drug concentration quickly. However, work remains to understand how to determine what target exposure is needed for an individual patient, and whether the combination of POC assays and dashboards presents a safe approach with substantial outcome benefit over the current standard of care.
单克隆抗体 (mAb) 被引入到炎症性肠病 (IBD) 的治疗中是一个重要的医学里程碑。mAb 已被证明是安全有效的 IBD 治疗方法。然而，很大一部分患者要么最初没有反应，要么在治疗一段时间后失去反应。尽管 IBD 的治疗结果与一些因素有关，但治疗失败的一个原因可能是 mAb 暴露水平低。因此，胃肠病学家已开始使用治疗药物监测 (TDM) 来指导剂量调整。然而，尽管 TDM 有益，但它不能提供足够的信息来有效调整剂量。mAb 的药代动力学 (PK) 和药效动力学 (PD) 很复杂，有许多因素会影响 mAb 的 PK 和 PD。基于贝叶斯 PK 模型的仪表盘指导剂量概念使医生能够将 TDM 与影响 mAb PK 的因素结合起来，更有效地实现个体化治疗。TDM 的一个问题是检测结果的周转时间缓慢，要么需要再次就诊进行样本检测，要么要在后续剂量而不是当前剂量时对 TDM 结果做出反应。正在开发新的 mAb 即时检测 (POC) 检测方法，这将使医生能够快速确定药物浓度。然而，仍需要研究如何确定个体患者需要的目标暴露量，以及 POC 检测和仪表盘的组合是否比当前的护理标准更安全，是否能带来实质性的临床获益。
