Division of Gastroenterology, Department of Medicine, Siriraj Hospital, Mahidol University, Salaya, Thailand.
Department of Gastroenterology and Hepatology, Concord Repatriation General Hospital, Sydney, New South Wales, Australia.
Aliment Pharmacol Ther. 2024 Nov;60(9):1234-1243. doi: 10.1111/apt.18228.
There are a plethora of therapeutic options for the management of inflammatory bowel disease (IBD). Despite this, clinical outcomes with standard dosing often fall short of established targets. While efforts centre on developing novel therapies, there is an ongoing need to optimise the use of existing agents.
To focus on strategies to optimise response to biologic (monoclonal antibody) therapies in IBD, including use of therapeutic drug monitoring (TDM).
An extensive review of the published literature.
TDM is a strategy aimed at enhancing the effectiveness of drugs with variable exposure-response relationships by measuring serum concentrations of biologic therapies and detecting neutralising antibodies. Reactive TDM is performed when therapeutic goals have not been achieved. Tumour necrosis factor alpha (TNF) inhibitors are the treatment class most frequently associated with immunogenicity and loss of response. Immunogenicity can be reduced through avoidance of low serum drug concentrations by dose optimisation or use of concomitant immunomodulator therapy. Subtherapeutic dosing in the absence of antidrug antibodies is best managed by dose escalation or dose interval reduction. Persistent neutralising drug antibodies necessitate switching to an alternative therapy. Proactively ensuring adequate serum trough levels might help sustain treatment durability and prevent loss of response. Newer non-TNF inhibitors demonstrate less robust exposure-response relationships, and TDM may not prove as beneficial.
In the treat-to-target paradigm of IBD treatment, optimising treatment effect with dose optimisation, which may involve strategies including TDM, increases the likelihood of achieving clinical remission and may accomplish deeper levels of remission beyond symptom control.
有许多治疗方法可用于炎症性肠病（IBD）的管理。尽管如此，标准剂量的临床疗效往往达不到既定目标。虽然人们的努力集中在开发新的治疗方法上，但仍需要不断优化现有药物的使用。
专注于优化生物（单克隆抗体）疗法在 IBD 中的反应的策略，包括使用治疗药物监测（TDM）。
对已发表文献进行广泛综述。
TDM 是一种旨在通过测量生物疗法的血清浓度和检测中和抗体来提高具有可变暴露-反应关系的药物有效性的策略。当未达到治疗目标时进行反应性 TDM。肿瘤坏死因子-α（TNF）抑制剂是最常与免疫原性和反应丧失相关的治疗类别。通过优化剂量或同时使用免疫调节剂治疗来避免低血清药物浓度，可以降低免疫原性。在没有抗体的情况下，低于治疗剂量最好通过增加剂量或减少剂量间隔来管理。持续存在的中和药物抗体需要转换为替代疗法。积极确保足够的血清谷浓度可能有助于维持治疗的持久性并防止反应丧失。新型非 TNF 抑制剂显示出较弱的暴露-反应关系，TDM 可能没有证明是有益的。
在 IBD 治疗的靶向治疗范例中，通过优化剂量（可能包括 TDM 策略）来优化治疗效果，可以增加实现临床缓解的可能性，并可能在症状控制之外达到更深层次的缓解水平。
