Vande Casteele Niels, Gils Ann
Department of Pharmaceutical and Pharmacological Sciences, Therapeutic and Diagnostic Antibodies, KU Leuven - University of Leuven, Herestraat, Leuven, Belgium.
J Clin Pharmacol. 2015 Mar;55 Suppl 3:S39-50. doi: 10.1002/jcph.374.
Since anti-tumor necrosis factor (TNF) antibodies were introduced to treat patients with inflammatory bowel diseases, short- and long-term clinical and endoscopic endpoints can be achieved that were unreachable with conventional anti-inflammatory agents. Although a large proportion of patients (70-90%) initially respond to the treatment, remission rates after induction are still low (20-50%) and patients are at risk to lose response to the drug over time. This inter-individual variability in response is likely to be influenced by the observed inter-individual variability in pharmacokinetics. By extensively reviewing the literature, we evaluated the potential role of therapeutic drug monitoring to optimize dosing of anti-TNF drugs. Thereby we emphasize some of the pharmacokinetic cornerstones that can help to understand the observed concentration-effect relationship. After discussing some of the most commonly used assays to measure anti-TNF drug and anti-drug antibody concentrations, we reviewed the application of those tests and their potential clinical value in retrospective and prospective studies.
自从引入抗肿瘤坏死因子(TNF)抗体来治疗炎症性肠病患者以来,已经能够实现传统抗炎药物无法达到的短期和长期临床及内镜终点。尽管很大一部分患者(70-90%)最初对治疗有反应,但诱导缓解率仍然很低(20-50%),并且随着时间的推移患者有失去对药物反应的风险。这种个体间反应的变异性很可能受到观察到的个体间药代动力学变异性的影响。通过广泛查阅文献,我们评估了治疗药物监测在优化抗TNF药物给药方面的潜在作用。因此,我们强调了一些药代动力学的基石,这些基石有助于理解观察到的浓度-效应关系。在讨论了一些最常用的检测抗TNF药物和抗药物抗体浓度的方法后,我们回顾了这些检测方法在回顾性和前瞻性研究中的应用及其潜在的临床价值。