University of Pittsburgh School of Pharmacy, Pittsburgh, PA, USA.
Janssen Research & Development, LLC, Spring House, PA, USA.
J Clin Pharmacol. 2018 Jul;58(7):864-876. doi: 10.1002/jcph.1084. Epub 2018 Feb 20.
Therapeutic drug monitoring (TDM), or the measurement of drug concentrations in blood and antidrug antibodies, for biologic therapies used to treat inflammatory bowel disease (IBD) is an area of growing interest within the IBD community. When there is a definable relationship between drug concentration and clinical effect, blood concentration of biologics (and antidrug antibodies assessment) could be used to predict patient response and to titrate the biologics to maximize therapeutic benefit. This dose individualization has been proven to be more efficacious and cost-effective than empiric dose adjustment and can better guide therapeutic decisions regarding therapy withdrawal or switch. Appropriate implementation and interpretation of drug concentration measurement in TDM are essential to ensure full clinical benefit. Factors that need to be considered include sources of variability, timing of blood sampling, dosing history, analytical performance, immunogenicity, comedications, and clinical status of the patients. Desired target concentrations for biologics used in IBD have not been clearly determined yet. Published concentration thresholds differed widely for a given biologic, indicating a lack of consistent information. Factors other than drug concentration that may contribute to the dose-response variation are largely missing in the current TDM setting. A target range is likely preferable to a single value for TDM of biologics in IBD, and additional prospective research needs to be conducted in order to establish these ranges. Moving forward, TDM may be combined with pharmacodynamic end points and modeling and simulation tools for improved therapeutic benefit in IBD.
治疗药物监测（TDM），或测量用于治疗炎症性肠病（IBD）的生物治疗药物的血液浓度和抗药物抗体，是 IBD 领域日益关注的领域。当药物浓度与临床效果之间存在明确关系时，生物制剂的血液浓度（和抗药物抗体评估）可用于预测患者反应，并调整生物制剂的剂量以最大化治疗效果。这种个体化剂量已被证明比经验性剂量调整更有效且更具成本效益，并且可以更好地指导关于停止或转换治疗的治疗决策。适当实施和解释 TDM 中的药物浓度测量对于确保充分的临床获益至关重要。需要考虑的因素包括变异性来源、采血时间、剂量史、分析性能、免疫原性、合并用药和患者的临床状况。IBD 中使用的生物制剂的理想目标浓度尚未明确确定。对于给定的生物制剂，已发表的浓度阈值差异很大，表明缺乏一致的信息。在当前的 TDM 环境中，除药物浓度外，可能导致剂量反应变异的其他因素在很大程度上缺失。对于 IBD 中的生物制剂 TDM，目标范围可能比单个值更可取，需要进行更多的前瞻性研究以确定这些范围。展望未来，TDM 可能与药效学终点和建模与模拟工具相结合，以提高 IBD 的治疗效果。
