在炎症性肠病患儿中进行前瞻性治疗药物监测和维得利珠单抗剂量优化。
Proactive therapeutic drug monitoring and vedolizumab dose optimization in children with inflammatory bowel disease.
机构信息
Division of Gastroenterology and Hepatology, Nationwide Children's Hospital, Columbus, Ohio, USA.
Department of Pharmacy, Nationwide Children's Hospital, Columbus, Ohio, USA.
出版信息
J Pediatr Gastroenterol Nutr. 2024 Apr;78(4):853-861. doi: 10.1002/jpn3.12132. Epub 2024 Jan 25.
OBJECTIVES
Therapeutic drug monitoring (TDM) and dose optimization have been shown to improve clinical outcomes with antitumor necrosis factor and recent studies in adults suggest an exposure-response relationship with drug levels associated with improved clinical outcomes. However, these levels are not universally recognized as therapeutic targets for vedolizumab dosing. We aimed to assess the impact of a TDM quality improvement (QI) initiative on 52-week clinical outcomes and describe proactively obtained vedolizumab levels during the induction period in children with inflammatory bowel disease (IBD).
METHODS
A QI initiative to proactively obtain TDM levels at Week 6 was implemented in 2019. A retrospective review of pediatric patients with IBD treated with vedolizumab from 2018 to 2022 was performed. Baseline demographic data, medication dosing details, disease characteristics, lab results, and 12-month clinical outcomes were recorded. For this study, we defined therapeutic target levels (>20 μg/mL at Week 6 and >12 μg/mL during maintenance) based on existing data correlating these levels with improved clinical outcomes.
RESULTS
Fifty-nine patients (31 Crohn disease [CD], 28 ulcerative colitis [UC]/indeterminate colitis [IC]) were included in the study. In total, 68% (40/59) of patients had vedolizumab levels at Week 6 and 90% (53/59) had levels drawn at Week 6 or 14. Thirty-five percent of Week 6 trough levels were below our defined target of 20 μg/mL. Fifty-two of 59 patients had available data at 52 weeks. Over 80% (42/52) of patients remained on vedolizumab 52 weeks after initiation (CD 79% [23/29], UC/IC 83% [19/23]). Sixty-two percent (26/42) of patients that remained on vedolizumab at 52 weeks were treated with an intensified dosing interval of <8 weeks. Thirty-one of these 42 (74%) were in clinical remission (CR) rate at 52 weeks with 29/42 (69%) in corticosteroid-free remission. The CR rate for the entire cohort including those who discontinued therapy due to a lack of efficacy before 52 weeks was 60% (31/52).
CONCLUSION
Proactive TDM and early dose optimization with vedolizumab may improve drug durability and clinical outcomes in pediatric patients with IBD.
目的
治疗药物监测（TDM）和剂量优化已被证明可以改善抗肿瘤坏死因子的临床结果，最近的成人研究表明，药物水平与临床结果的改善存在暴露-反应关系。然而，这些水平并未被普遍认为是 vedolizumab 剂量的治疗目标。我们旨在评估 TDM 质量改进（QI）计划对 52 周临床结果的影响，并描述在儿童炎症性肠病（IBD）诱导期主动获得的 vedolizumab 水平。
方法
2019 年实施了一项主动获得 TDM 水平的 QI 计划，在第 6 周进行。对 2018 年至 2022 年接受 vedolizumab 治疗的儿科 IBD 患者进行了回顾性研究。记录了基线人口统计学数据、药物剂量细节、疾病特征、实验室结果和 12 个月的临床结果。在这项研究中，我们根据现有的数据，将与改善临床结果相关的水平定义为治疗目标水平（第 6 周>20μg/ml，维持期>12μg/ml）。
结果
共有 59 名患者（31 名克罗恩病[CD]，28 名溃疡性结肠炎[UC]/不确定结肠炎[IC]）纳入研究。总共 68%（40/59）的患者在第 6 周时进行了 vedolizumab 水平检测，90%（53/59）在第 6 周或第 14 周进行了水平检测。35%的第 6 周谷浓度低于我们定义的 20μg/ml 的目标值。59 名患者中有 52 名在 52 周时有可用数据。超过 80%（42/52）的患者在起始后 52 周仍接受 vedolizumab 治疗（CD 79%[23/29]，UC/IC 83%[19/23]）。62%（26/42）在 52 周时仍接受 vedolizumab 治疗的患者接受了<8 周的强化给药间隔治疗。在这 42 名患者中，有 31 名（74%）在第 52 周达到临床缓解（CR），其中 29 名（69%）达到无皮质激素缓解。整个队列中，包括在 52 周前因疗效不佳而停止治疗的患者，CR 率为 60%（52/87）。
结论
主动进行 TDM 并在 vedolizumab 治疗中早期进行剂量优化，可能会提高儿科 IBD 患者的药物持久性和临床结果。
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