Anti-TNF Monoclonal Antibodies in Inflammatory Bowel Disease: Pharmacokinetics-Based Dosing Paradigms
Anti-TNF Monoclonal Antibodies in Inflammatory Bowel Disease: Pharmacokinetics-Based Dosing Paradigms
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DOI：
10.1038/clpt.2011.328
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发表时间：
2012-04-01
影响因子：
6.7
通讯作者：
Sandborn, William J.
中科院分区：
文献类型：
--
作者：
Ordas, Ingrid;Mould, Diane R.;Sandborn, William J.
克罗恩病和溃疡性结肠炎是由免疫失调引起的慢性炎症性疾病。常规药物治疗失败的患者需要使用单克隆抗体（mAb）进行生物治疗。尽管mAb对于诱导和维持临床缓解非常有效，但并非所有患者都有反应，并且很高比例的患者随着时间的推移而失去反应。与应答丧失相关的一个因素是免疫原性，由此抗药抗体的产生加速mAb清除。然而，与患者和疾病特征相关的其他因素也会影响mAb的药代动力学。这些因素包括性别、体型、伴随使用免疫抑制剂、疾病类型、血清白蛋白浓度和全身炎症程度。由于维持临床有效浓度以提供最佳临床应答非常重要，并且药物暴露受患者因素影响，因此更好地了解mAb的药理学将最终导致更好的患者护理。
Crohn's disease and ulcerative colitis are chronic inflammatory disorders resulting from immune dysregulation. Patients who fail conventional medical therapy require biological treatment with monoclonal antibodies (mAbs). Although mAbs are highly effective for induction and maintenance of clinical remission, not all patients respond, and a high proportion of patients lose response overtime. One factor associated with loss of response is immunogenicity, whereby the production of antidrug antibodies accelerates mAb clearance. However, other factors related to patient and disease characteristics also influence the pharmacokinetics of mAbs. These factors include gender, body size, concomitant use of immunosuppressive agents, disease type, serum albumin concentration, and the degree of systemic inflammation. Because it is important to maintain clinically effective concentrations to provide optimal clinical response and drug exposure is affected by patient factors, a better understanding of the pharmacology of mAbs will ultimately result in better patient care.