*Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth-Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; †Division of Gastroenterology, University of California San Diego, La Jolla, California; ‡Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium; and §Department of Pharmaceutical and Pharmacological Sciences, Laboratory for Therapeutic and Diagnostic Antibodies, Katholieke Universiteit Leuven, Leuven, Belgium.
Inflamm Bowel Dis. 2017 Sep;23(9):1510-1515. doi: 10.1097/MIB.0000000000001231.
Anti-tumor necrosis factor (TNF) therapy has revolutionized the treatment of inflammatory bowel disease (IBD). However, up to 30% of patients with IBD show no clinical benefit and are defined as having a primary nonresponse. Primary nonresponse to a biologic can be attributed to either pharmacokinetic or pharmacodynamic issues, such as those involved in secondary loss of response. Pharmacokinetic issues are linked to undetectable or subtherapeutic drug concentrations because of either an accelerated non-immune-mediated clearance or immunogenicity and the development of antidrug antibodies, whereas pharmacodynamic issues are likely related to "non-TNF driven" disease. Therapeutic drug monitoring (TDM), defined as the evaluation of drug concentrations and antidrug antibodies, has been proven effective for optimizing anti-TNF therapy in IBD. Nevertheless, most of the data for TDM relate to patients losing response during maintenance therapy, whereas much less is known about the therapeutic drug window and use of TDM during anti-TNF induction therapy. Recent exposure-response relationship studies, though, demonstrate that high serum anti-TNF drug concentrations during and early after induction therapy are associated with favorable therapeutic outcomes in IBD. This suggests that early optimization of anti-TNF therapy may prevent some of the primary nonresponse related to pharmacokinetic issues (low drug concentrations) and lead to better short- and long-term outcomes. This review will focus on the role of TDM during the induction phase of anti-TNF therapy.
抗肿瘤坏死因子（TNF）治疗已经彻底改变了炎症性肠病（IBD）的治疗方法。然而，高达 30%的 IBD 患者没有临床获益，被定义为原发性无应答。对生物制剂的原发性无应答可能归因于药代动力学或药效动力学问题，例如与继发性应答丧失相关的问题。药代动力学问题与不可检测或治疗性药物浓度有关，这是由于非免疫介导的清除率加快或免疫原性以及抗药物抗体的产生，而药效动力学问题可能与“非 TNF 驱动”的疾病有关。治疗药物监测（TDM）定义为评估药物浓度和抗药物抗体，已被证明对优化 IBD 的抗 TNF 治疗有效。然而，大多数 TDM 数据都与在维持治疗期间失去应答的患者有关，而在抗 TNF 诱导治疗期间，TDM 的治疗药物窗口和应用知之甚少。最近的暴露-反应关系研究表明，在诱导治疗期间和早期，血清中高浓度的抗 TNF 药物与 IBD 的良好治疗结果相关。这表明早期优化抗 TNF 治疗可能预防与药代动力学问题（药物浓度低）相关的一些原发性无应答，并导致更好的短期和长期结果。这篇综述将重点介绍 TDM 在抗 TNF 治疗诱导阶段的作用。
