Desai Devendra C, Dherai Alpa J, Strik Anne, Mould Diane R
Division of Gastroenterology, PD Hinduja Hospital, Veer Savarkar Marg, Mahim, Mumbai, India.
Department of Laboratory Medicine, PD Hinduja Hospital, Veer Savarkar Marg, Mahim, Mumbai, India.
J Clin Pharmacol. 2023 Apr;63(4):480-489. doi: 10.1002/jcph.2189. Epub 2022 Dec 29.
Although biological agents have revolutionized the management of inflammatory bowel diseases (IBDs), a significant proportion of patients show primary non-response or develop secondary loss of response. Therapeutic drug monitoring (TDM) is advocated to maintain the efficacy of biologic agents. Reactive TDM can rationalize the management of primary non-response and secondary loss of response and has shown to be more cost-effective compared with empiric dose escalation. Proactive TDM is shown to increase clinical remission and the durability of the response to a biologic agent. However, the efficacy of proactive and reactive TDM has been questioned in recent studies and meta-analyses. Hence, we need a different approach to TDM, which addresses inflammatory burden, the individual patient, and disease factors. Bayesian approaches, which use population pharmacokinetic models, enable clinicians to make better use of TDM for dose adjustment. With rapid improvement in computer technology, these Bayesian model-based software packages are now available for clinical use. Bayesian dashboard systems allow clinicians to apply model-based dosing to understand an individual's pharmacokinetics and achieve a target serum drug concentration. The model is updated using previously measured drug concentrations and relevant patient factors, such as body weight, C-reactive protein, and serum albumin concentration, to maintain effective drug concentrations in the serum. Initial studies have found utility for the Bayesian approach in induction and maintenance, in adult and pediatric patients, in clinical trials, and in real-life situations for patients with IBD treated with infliximab. This needs confirmation in larger studies. This article reviews the Bayesian approach to therapeutic drug monitoring in IBD.
尽管生物制剂彻底改变了炎症性肠病（IBD）的治疗方式，但仍有相当一部分患者表现出原发性无反应或出现继发性反应丧失。提倡进行治疗药物监测（TDM）以维持生物制剂的疗效。反应性TDM可以使原发性无反应和继发性反应丧失的管理更加合理，并且已证明与经验性剂量递增相比更具成本效益。前瞻性TDM已显示可提高临床缓解率以及对生物制剂反应的持久性。然而，近期的研究和荟萃分析对前瞻性和反应性TDM的疗效提出了质疑。因此，我们需要一种不同的TDM方法，该方法要考虑炎症负担、个体患者和疾病因素。使用群体药代动力学模型的贝叶斯方法使临床医生能够更好地利用TDM进行剂量调整。随着计算机技术的快速发展，这些基于贝叶斯模型的软件包现已可供临床使用。贝叶斯仪表板系统使临床医生能够应用基于模型的给药方法来了解个体的药代动力学并达到目标血清药物浓度。该模型使用先前测量的药物浓度和相关患者因素（如体重、C反应蛋白和血清白蛋白浓度）进行更新，以维持血清中的有效药物浓度。初步研究发现，贝叶斯方法在成人和儿科患者的诱导和维持治疗中、在临床试验以及英夫利昔单抗治疗的IBD患者的实际临床情况中均有用处。这需要在更大规模的研究中得到证实。本文综述了IBD治疗药物监测的贝叶斯方法。
