Ma Christopher, Battat Robert, Jairath Vipul, Vande Casteele Niels
Division of Gastroenterology and Hepatology, University of Calgary, 3280 Hospital Drive NW, Calgary, Alberta, T2N 4Z6, Canada.
Robarts Clinical Trials, Inc., #200, 100 Dundas Street, London, Ontario, N6A 5B6, Canada.
Curr Treat Options Gastroenterol. 2019 Mar;17(1):127-145. doi: 10.1007/s11938-019-00222-9.
Therapeutic drug monitoring (TDM) is increasingly utilized as a strategy to optimize inflammatory bowel disease (IBD) therapeutics. As management paradigms have evolved towards treat-to-target strategies, there has been growing interest in expanding the role of TDM to guide drug optimization for achieving objective endpoints. This review summarizes the evidence for using TDM with biologic and oral small-molecule therapies, evaluates the role of reactive versus proactive TDM in treatment algorithms, and identifies potential future applications for TDM.
Achieving therapeutic drug concentrations has been associated with important clinical, endoscopic, and histologic outcomes in IBD. However, the optimal drug concentration varies by therapeutic agent, disease phenotype, inflammatory burden, phase of treatment, and target outcome. Traditionally, TDM has been used reactively to define pharmacokinetic versus mechanistic failures after loss of response to a tumor necrosis factor-α (TNF) antagonist and while observational data suggests a benefit to proactive TDM, this has not been definitively confirmed in prospective randomized controlled trials. The role of TDM in optimizing vedolizumab, ustekinumab, and tofacitinib remains unclear, given differences in pharmacokinetics and immunogenicity compared to TNF antagonists. Measuring drug action at the site of inflamed tissue may provide additional insights into treatment optimization. The use of TDM offers the possibility of a more personalized treatment approach for patients with IBD. High-quality studies are needed to delineate the role of proactive TDM for maintaining remission, for optimizing induction regimens, and for novel agents.
治疗药物监测（TDM）越来越多地被用作优化炎症性肠病（IBD）治疗的一种策略。随着管理模式向达标治疗策略演变，人们越来越有兴趣扩大TDM的作用，以指导药物优化以实现客观终点。本综述总结了使用TDM进行生物制剂和口服小分子治疗的证据，评估了反应性与前瞻性TDM在治疗算法中的作用，并确定了TDM未来的潜在应用。
在IBD中，达到治疗药物浓度与重要的临床、内镜和组织学结果相关。然而，最佳药物浓度因治疗药物、疾病表型、炎症负担、治疗阶段和目标结果而异。传统上，TDM一直是在对肿瘤坏死因子-α（TNF）拮抗剂失去反应后用于定义药代动力学与机制性失败，虽然观察数据表明前瞻性TDM有益，但这在前瞻性随机对照试验中尚未得到明确证实。鉴于与TNF拮抗剂相比，维多珠单抗、乌司奴单抗和托法替布在药代动力学和免疫原性方面存在差异，TDM在优化这些药物方面的作用仍不明确。在炎症组织部位测量药物作用可能为治疗优化提供更多见解。使用TDM为IBD患者提供了更个性化治疗方法的可能性。需要高质量的研究来描述前瞻性TDM在维持缓解、优化诱导方案和新型药物方面的作用。
