Vaughn Byron P, Sandborn William J, Cheifetz Adam S
*Center for Inflammatory Bowel Diseases, Division of Gastroenterology, Beth-Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; †Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolis, Minnesota; and ‡Division of Gastroenterology, University of California San Diego, San Diego, California.
Inflamm Bowel Dis. 2015 Jun;21(6):1435-42. doi: 10.1097/MIB.0000000000000312.
Anti-TNF medications have revolutionized the care of patients with inflammatory bowel disease. However, despite an initial robust effect, loss of response is common and long-term results are disappointing. Much of this lack of durability may be due to inadequate dose optimization, and recent studies suggest a correlation between serum drug concentrations and clinical outcomes. Currently, in clinical practice, measurement of drug concentrations and antibodies to drug are typically performed only when a patient presents with active inflammatory bowel disease symptoms or during a potential immune-mediated reaction to anti-TNF ("reactive" setting). However, proactive monitoring of anti-TNF concentrations with titration to a therapeutic window (i.e., therapeutic concentration monitoring) represents a new strategy with many potential clinical benefits including prevention of immunogenicity, less need for IFX rescue therapy, and greater durability of IFX treatment. This review will cover the salient features of anti-TNF pharmacokinetics and pharmacodynamics and provide a rational approach for the use of anti-TNF concentration testing in both the reactive and proactive settings.
抗 TNF 药物彻底改变了炎症性肠病患者的治疗方式。然而，尽管最初有显著疗效，但反应丧失很常见，长期结果也令人失望。这种缺乏持久性的情况很大程度上可能是由于剂量优化不足，最近的研究表明血清药物浓度与临床结果之间存在关联。目前，在临床实践中，通常仅在患者出现活动性炎症性肠病症状时或在对抗 TNF 发生潜在免疫介导反应（“反应性”情况）期间才进行药物浓度和药物抗体的检测。然而，通过滴定至治疗窗对抗 TNF 浓度进行主动监测（即治疗浓度监测）代表了一种具有许多潜在临床益处的新策略，包括预防免疫原性、减少对英夫利昔单抗（IFX）救援治疗的需求以及提高 IFX 治疗的持久性。本综述将涵盖抗 TNF 药代动力学和药效学的显著特征，并为在反应性和主动监测情况下使用抗 TNF 浓度检测提供合理方法。
