Division of Gastroenterology, University of California, San Diego, La Jolla, California.
Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina.
Gastroenterology. 2017 Sep;153(3):835-857.e6. doi: 10.1053/j.gastro.2017.07.031. Epub 2017 Jul 31.
Therapeutic drug monitoring (TDM), which involves measurement of drug or active metabolite levels and anti-drug antibodies, is a promising strategy that can be used to optimize inflammatory bowel disease therapeutics. It is based on the premise that there is a relationship between drug exposure and outcomes, and that considerable inter-individual variability exists in how patients metabolize the drug (pharmacokinetics) and the magnitude and duration of response to therapy (pharmacodynamics). Therefore, the American Gastroenterological Association has prioritized clinical guidelines on the role of TDM in the management of inflammatory bowel disease. To inform these clinical guidelines, this technical review was developed in accordance with the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework for interventional and prognostic studies, and focused on the application of TDM for biologic therapy, specifically anti-tumor necrosis factor-α agents, and for thiopurines. Focused questions address the benefits and risks of a strategy of reactive TDM (in patients with active inflammatory bowel disease) to guide treatment changes compared with empiric treatment changes, and the benefits and risks of a strategy of routine proactive TDM (during routine clinical care in patients with quiescent disease) compared with no routine TDM. Additionally, the review addresses the benefits and risks of routine measurement of thiopurine methyltransferase enzyme activity or genotype before starting thiopurine therapy compared with empiric weight-based dosing and explores the performance of different trough drug concentrations for anti-tumor necrosis factor agents and thiopurines to inform clinical decision making when applying TDM in a reactive setting. Due to a paucity of data, this review does not address the role of TDM for more recently approved biologic agents, such as vedolizumab or ustekinumab.
治疗药物监测（therapeutic drug monitoring，TDM）涉及药物或活性代谢物水平以及抗药物抗体的测量，是一种很有前途的策略，可以用于优化炎症性肠病的治疗。它基于这样一个前提，即药物暴露与结果之间存在关系，并且患者代谢药物（药代动力学）以及对治疗的反应程度和持续时间（药效动力学）存在相当大的个体间差异。因此，美国胃肠病学会已将 TDM 在炎症性肠病管理中的作用的临床指南列为优先事项。为了为这些临床指南提供信息，本技术综述是根据干预性和预后性研究的 GRADE（推荐评估、制定与评价）框架制定的，重点关注 TDM 在生物治疗（特别是抗肿瘤坏死因子-α 制剂和硫嘌呤）中的应用。重点问题涉及与经验性治疗改变相比，在有活性炎症性肠病患者中采用反应性 TDM（therapeutic drug monitoring）策略来指导治疗改变的获益和风险，以及在疾病缓解期常规临床护理中采用常规主动 TDM（routinely proactive TDM）策略与不进行常规 TDM 的获益和风险。此外，本综述还探讨了在开始使用硫嘌呤治疗之前常规测量硫嘌呤甲基转移酶酶活性或基因型与经验性基于体重的剂量相比的获益和风险，并探讨了不同谷底药物浓度在抗肿瘤坏死因子制剂和硫嘌呤中的性能，以便在反应性环境中应用 TDM 时为临床决策提供信息。由于数据有限，本综述未涉及治疗药物监测在最近批准的生物制剂（如 vedolizumab 或 ustekinumab）中的作用。
