Hematology Center, Beijing Children's Hospital, Capital Medical University, Beijing, China.
Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Haemophilia. 2021 Jul;27(4):e450-e457. doi: 10.1111/hae.14336. Epub 2021 May 20.
The traditional weight-based dosing regimen can lead to under- or overdosage due to the interindividual variability of pharmacokinetic (PK) parameters. PK-guided prophylaxis can be an optimized therapy choice.
This study aimed to investigate the clinical outcomes of PK-guided prophylaxis in 46 boys with severe haemophilia A.
Forty-six boys with severe haemophilia A were enrolled in Beijing Children's Hospital. The PK tests were performed using a five-point assay. PK parameters were calculated using WinNonlin software. The dosing regimen and bleeding rates recorded during the observation period. The adjustment was based on PK evaluation, bleeding details, doctor's advice and patients' choice.
The half-life time, in vivo recovery and clearance of Kovaltry were 14.34 ± 2.68 h, 1.78 ± 0.29 kg/dl and 3.38 ± 0.94 ml/kg/h, respectively. In 18 patients without any change in the dosing regimen, the trough level was 4.0 ± 2.41 IU/dl and the bleeding rates were similar after PK tests. For patients with a higher trough level after adjustment, higher dose and frequency were observed, as well as a higher trough level. Also, reduced annual bleeding rate (ABR), annual joint bleeding rate and annual spontaneous bleeding rate (ASBR) were found. In five patients with a reduced trough level, lower infusion frequency and weekly coagulation factor VIII (FVIII) consumption were observed, with no statistically significant difference in ABR and ASBR.
PK-guided prophylaxis can help haemophiliac patients improve quality of life by decreasing bleeds with appropriate FVIII consumption and reducing infusion frequency without increments in bleeds, thus optimizing haemophilia treatment.
传统的基于体重的给药方案由于药代动力学（PK）参数的个体间变异性，可能导致剂量不足或过量。PK 指导的预防治疗可能是一种优化的治疗选择。
本研究旨在探讨 46 例重型血友病 A 患儿 PK 指导预防治疗的临床结局。
本研究纳入 46 例在北京儿童医院接受治疗的重型血友病 A 患儿。采用五点法进行 PK 检测，使用 WinNonlin 软件计算 PK 参数。记录观察期间的给药方案和出血率。根据 PK 评估、出血情况、医生建议和患者选择进行调整。
Kovaltry 的半衰期、体内回收率和清除率分别为 14.34±2.68 h、1.78±0.29 kg/dl 和 3.38±0.94 ml/kg/h。在未改变给药方案的 18 例患者中， trough 水平为 4.0±2.41 IU/dl，PK 检测后出血率相似。对于调整后 trough 水平较高的患者，观察到更高的剂量和频率，以及更高的 trough 水平。同时，发现年出血率（ABR）、年关节出血率和年自发性出血率（ASBR）降低。在 5 例 trough 水平降低的患者中，观察到输注频率降低和每周凝血因子 VIII（FVIII）消耗减少，但 ABR 和 ASBR 无统计学差异。
PK 指导的预防治疗可通过适当的 FVIII 消耗减少出血，降低输注频率，同时不增加出血，从而改善血友病患者的生活质量，优化血友病治疗。
