Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics, Ministry of Education, Beijing, China.
Haemophilia. 2021 May;27(3):e340-e346. doi: 10.1111/hae.14276. Epub 2021 Mar 1.
Kovaltry (BAY81-8973) is an unmodified full-length factor VIII (FVIII) concentrate that enhances the pharmacokinetic (PK) profiles as compared to some other standard half-life time FVIII concentrates. However, the PK of Kovaltry in haemophiliac patients aged <12 years has not been reported previously.
To investigate the pharmacokinetics and clinical outcomes of Kovaltry in 35 paediatric patients aged <12 years.
A total of 35 boys with severe haemophilia A were enrolled from August 2019 to May 2020 in Beijing Children's Hospital. After 72-hour washout, PK tests were performed post-infusion of 50 IU/kg Kovaltry in a five-timepoint assay. WinNonlin software was used to generate individual PK parameters. The dose, frequency and bleeding details were collected within the first 6 months after switching to Kovaltry from other FVIII concentrates.
Compared to the blood group O, patients with blood group non-O showed longer mean half-life (t ) (p < .01), lower mean clearance (CL) (p = .01) and similar in vivo recovery (IVR) (p = .51). Higher von Willebrand factor antigen (VWF:Ag) level was correlated to longer t (p < .0001) and lower CL (p < .01). IVR was correlated to body mass index (BMI) (p < .0001). Patients with trough level >3 IU/dL demonstrated lower annual bleeding rate (ABR) (p < .01), annual joint bleeding rate (AJBR) (p < .01) and annual spontaneous bleeding rate (ASBR) (p < .01).
This study firstly reported the PK profiles of Kovaltry in 35 paediatric patients <12 years old. The great inter-individual variability of PK parameters was also confirmed in these patients. VWF:Ag and blood group were major influencing factors of t and CL of Kovaltry, while BMI was a vital predictor for IVR. Patients with high trough FVIII level in routine prophylaxis had reduced bleeding rates.
Kovaltry（BAY81-8973）是一种未经修饰的全长因子 VIII（FVIII）浓缩物，与一些其他标准半衰期 FVIII 浓缩物相比，其药代动力学（PK）特征得到增强。然而，先前尚未报道过 Kovaltry 在<12 岁的血友病患者中的 PK 情况。
研究 35 名<12 岁的儿科患者使用 Kovaltry 的药代动力学和临床结果。
2019 年 8 月至 2020 年 5 月，北京儿童医院共招募了 35 名严重甲型血友病男孩。在经过 72 小时洗脱期后，对 35 名男孩进行了单次输注 50IU/kg Kovaltry 的 PK 测试，采用五时间点分析法。使用 WinNonlin 软件生成个体 PK 参数。在从其他 FVIII 浓缩物切换至 Kovaltry 的前 6 个月内，收集了剂量、频率和出血情况的详细信息。
与 O 型血相比，非 O 型血患者的平均半衰期（t）更长（p<.01），平均清除率（CL）更低（p=.01），体内回收率（IVR）相似（p=.51）。较高的血管性血友病因子抗原（VWF:Ag）水平与更长的 t（p<.0001）和更低的 CL（p<.01）相关。IVR 与体重指数（BMI）相关（p<.0001）。在常规预防治疗中，Kovaltry 谷浓度>3IU/dL 的患者的年出血率（ABR）（p<.01）、年关节出血率（AJBR）（p<.01）和年自发性出血率（ASBR）（p<.01）更低。
本研究首次报道了 35 名<12 岁的儿科患者使用 Kovaltry 的 PK 特征。在这些患者中，PK 参数的个体间差异很大。VWF:Ag 和血型是 Kovaltry t 和 CL 的主要影响因素，而 BMI 是 IVR 的重要预测因子。常规预防治疗中 Kovaltry 谷浓度较高的患者出血率降低。
