Papamichael Konstantinos, Cheifetz Adam S
Division of Gastroenterology, Center for Inflammatory Bowel Diseases, Beth-Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Frontline Gastroenterol. 2016 Oct;7(4):289-300. doi: 10.1136/flgastro-2016-100685. Epub 2016 Feb 26.
Anti-tumour necrosis factor (TNF) therapies, such as infliximab, adalimumab, certolizumab pegol and golimumab, have been proven to be effective for the treatment of patients with Crohn's disease and ulcerative colitis. However, 10%-30% of patients with inflammatory bowel disease (IBD) show no initial clinical benefit to anti-TNF therapy (primary non-response), and over 50% after an initial favourable outcome will lose response over time (secondary loss of response (SLR)). Numerous recent studies in IBD have revealed an exposure-response relationship suggesting a positive correlation between high serum anti-TNF concentrations and favourable therapeutic outcomes including clinical, biomarker and endoscopic remission, whereas antidrug antibodies have been associated with SLR and infusion reactions. Currently, therapeutic drug monitoring (TDM) is typically performed when treatment failure occurs either for SLR, drug intolerance (potential immune-mediated reaction) or infusion reaction (reactive TDM). Nevertheless, recent data demonstrate that proactive TDM and a treat-to-target (trough) therapeutic approach may more effectively optimise anti-TNF therapy efficacy, safety and cost. However, implementing TDM in real-life clinical practice is currently limited by the diversity in study design, therapeutic outcomes and assays used, which have hindered the identification of robust clinically relevant concentration thresholds. This review will focus mainly on the pharmacodynamic properties of anti-TNF therapy and the role of TDM in guiding therapeutic decisions in IBD.
抗肿瘤坏死因子（TNF）疗法，如英夫利昔单抗、阿达木单抗、赛妥珠单抗聚乙二醇化修饰物和戈利木单抗，已被证明对治疗克罗恩病和溃疡性结肠炎患者有效。然而，10%-30%的炎症性肠病（IBD）患者对抗TNF治疗无初始临床获益（原发性无反应），超过50%的患者在初始取得良好疗效后会随着时间推移失去反应（继发性反应丧失（SLR））。IBD领域最近的大量研究揭示了暴露-反应关系，表明高血清抗TNF浓度与良好的治疗结果（包括临床、生物标志物和内镜缓解）之间呈正相关，而抗药抗体与SLR和输液反应有关。目前，治疗药物监测（TDM）通常在治疗失败时进行，无论是因SLR、药物不耐受（潜在的免疫介导反应）还是输液反应（反应性TDM）。然而，最近的数据表明，前瞻性TDM和达标（谷浓度）治疗方法可能更有效地优化抗TNF治疗的疗效、安全性和成本。然而，在现实临床实践中实施TDM目前受到研究设计、治疗结果和所用检测方法多样性的限制，这阻碍了确定可靠的临床相关浓度阈值。本综述将主要关注抗TNF治疗的药效学特性以及TDM在指导IBD治疗决策中的作用。
