药代动力学(PK)指导的给药用于个体化因子(F)VIII和FIX替代疗法。
■这项研究调查了在血友病A和B中PK指导的预防性给药因子浓缩物的可靠性和可行性。
■在这个多中心中,前瞻性队列研究,所有年龄的血友病患者均接受了基于个体PK参数的因子浓缩物预防性治疗.随访期间,将每个患者至少4个测量的FVIII/FIX水平与通过贝叶斯预测获得的相应预测水平进行比较.当测量的FVIII/FIX水平的≥80%在预测的±25%(相对误差)内时,预测性能被定义为足够。此外,计算平均绝对误差和平均误差。在事后分析中,评估预测性能,允许最大绝对误差为1(波谷),5(中),和15(峰值)IU/dL。五点量表问卷讨论了PK指南的可行性。
■我们纳入了50名患者(中位年龄,19年;范围:2-72年)。中位随访时间为36周。71%的水平(58%的低谷,83%中期,和80%的峰值)在预测的±25%内。平均绝对误差为0.8(波谷),2.0(中),和8.6(峰值)IU/dL。在事后分析中,81%(低谷),96%(中),82%(峰值)的水平在设定的限度内。患者报告负担低,满意度高。
■根据事后分析,PK指导的给药是可靠的,基于在大多数情况下被认为是临床无关的低绝对误差。预定义的预测性能是在中和峰值因子水平上实现的,但由于测量不准确,在谷值因子水平上没有实现。PK指导似乎也是可行的。
UNASSIGNED: Pharmacokinetic (PK)-guided dosing is used to individualize factor (F)VIII and FIX replacement therapy.
UNASSIGNED: This study investigates the reliability and feasibility of PK-guided prophylactic dosing of factor concentrates in hemophilia A and B.
UNASSIGNED: In this multicenter, prospective cohort study, people of all ages with hemophilia received prophylactic treatment with factor concentrates based on individual PK parameters. During follow-up, at least 4 measured FVIII/FIX levels per patient were compared with corresponding predicted levels obtained by Bayesian forecasting. Predictive performance was defined as adequate when ≥80% of measured FVIII/FIX levels were within ±25% of prediction (relative error). Additionally, mean absolute error and mean error were calculated. In post hoc analyses, predictive performance was assessed allowing maximum absolute errors of 1 (trough), 5 (mid), and 15 (peak) IU/dL. Five-point scale questionnaires addressed feasibility of PK guidance.
UNASSIGNED: We included 50 patients (median age, 19 years; range: 2-72 years). Median follow-up was 36 weeks. Seventy-one percent of levels (58% trough, 83% mid, and 80% peak) were within ±25% of prediction. Mean absolute errors were 0.8 (trough), 2.0 (mid), and 8.6 (peak) IU/dL. In post hoc analyses, 81% (trough), 96% (mid), and 82% (peak) of levels were within set limits. Patients reported low burden and high satisfaction.
UNASSIGNED: PK-guided dosing was reliable according to post hoc analyses, based on low absolute errors that were regarded as clinically irrelevant in most cases. The predefined predictive performance was achieved in mid and peak factor levels but not in trough factor levels due to measurement inaccuracy. PK guidance also seemed feasible.