Frymoyer Adam, Piester Travis L, Park K T
*Department of Pediatrics, Division of Neonatal and Developmental Medicine †Department of Pediatrics, Division of Gastroenterology, Stanford University School of Medicine, Palo Alto, CA.
J Pediatr Gastroenterol Nutr. 2016 May;62(5):723-7. doi: 10.1097/MPG.0000000000001123.
Standard infliximab maintenance dosing of 5 mg/kg every 8 weeks may be inadequate to consistently achieve sufficient drug exposure to minimize loss of response or treatment failure in pediatric Crohn disease (CD). We aimed to determine the predicted infliximab trough concentrations in children with CD during maintenance therapy and the percentage of patients achieving target trough concentration >3 μg/mL.
A Monte Carlo simulation analysis was constructed using a published population pharmacokinetic model based on data from 112 children in the REACH trial. We assessed maintenance dosing strategies of 5, 7.5, and 10 mg/kg at dosing intervals of every 4, 6, and 8 weeks for children that differed by age, weight, albumin level, and concomitant immunomodulator therapy.
Based on the index case of a 10-year-old with CD receiving standard infliximab dosing with concomitant immunomodulator therapy, the median (interquartile range) simulated infliximab trough concentration at week 14 was 1.3 (0.5-2.7) μg/mL and 2.4 (1.0-4.8) μg/mL for albumin levels of 3 and 4 g/dL, respectively. Among 1000 simulated children in the model, trough concentration >3 μg/mL at week 14 was achieved 21% and 41% of the time for albumin levels of 3 and 4 g/dL, respectively.
Standard infliximab maintenance dosing in children with CD is predicted to frequently result in inadequate exposure, especially when albumin levels are low. Optimized dosing strategies for individual patients are needed to achieve sufficient drug exposure during infliximab maintenance therapy.
每8周5mg/kg的英夫利昔单抗标准维持剂量可能不足以持续实现足够的药物暴露，从而将儿童克罗恩病（CD）的反应丧失或治疗失败降至最低。我们旨在确定CD患儿维持治疗期间英夫利昔单抗的预测谷浓度，以及达到目标谷浓度>3μg/mL的患者百分比。
基于REACH试验中112名儿童的数据，使用已发表的群体药代动力学模型构建蒙特卡洛模拟分析。我们评估了年龄、体重、白蛋白水平和免疫调节剂联合治疗不同的儿童，每4、6和8周给药一次，剂量分别为5、7.5和10mg/kg的维持给药策略。
根据一名接受英夫利昔单抗标准剂量并联合免疫调节剂治疗的10岁CD患儿的索引病例，第14周模拟的英夫利昔单抗谷浓度中位数（四分位间距），白蛋白水平为3g/dL时为1.3（0.5 - 2.7）μg/mL，白蛋白水平为4g/dL时为2.4（1.0 - 4.8）μg/mL。在模型中模拟的1000名儿童中，第14周谷浓度>3μg/mL的情况，白蛋白水平为3g/dL时分别为21%，白蛋白水平为4g/dL时为41%。
预计CD患儿英夫利昔单抗标准维持剂量经常会导致暴露不足，尤其是白蛋白水平较低时。在英夫利昔单抗维持治疗期间，需要针对个体患者优化给药策略以实现足够的药物暴露。
