Djambas Khayat Claudia, Iosava Genadi, Romashevskaya Irina, Stasyshyn Oleksandra, Lopez Marta Julia, Pompa Maria Teresa, Rogosch Tobias, Seifert Wilfried
Hospital Hôtel Dieu de France, Saint Joseph University, Beirut, Lebanon.
Joint Stock Hematology and Transfusiology Research Institute, Tbilisi, Georgia.
J Blood Med. 2021 Jun 21;12:483-495. doi: 10.2147/JBM.S299130. eCollection 2021.
Plasma-derived von Willebrand factor/factor VIII (pdVWF/FVIII; VONCENTO, CSL Behring) is a high-concentration, low-volume, high-purity concentrate, with a high level of VWF high-molecular-weight multimers and a VWF/FVIII ratio of ~2.4:1.
This study (NCT01229007) investigated the pharmacokinetics (PK), efficacy and safety of pdVWF/FVIII in 35 previously treated (minimum 20 exposure days [EDs]) pediatric patients (<12 years) with severe hemophilia A. PK was evaluated with a single 50 IU FVIII/kg dose of pdVWF/FVIII. Efficacy and safety analyses were performed during on-demand treatment (n=17) or prophylaxis (n=18) for up to 100 EDs with a maximum study duration of 12 months.
PK profiles were similar for patients aged <6 years and those aged 6-12 years, and, as expected, the youngest patients had an increased clearance. On-demand patients reported 320 non-surgical bleeding (NSB) events and received a median number of 29.0 infusions (median dose 34.2 IU FVIII/kg). Hemostatic efficacy was assessed by the investigator as excellent/good in all cases (24%/76%). The 18 patients in the prophylaxis arm experienced 173 NSB events (97 NSBs [56%] in three patients). Five patients (28%) had no NSB events. Overall, patients received a median number of 92 infusions (median dose 30.6 IU FVIII/kg). The majority of bleeds (92%) were successfully controlled with only one infusion. Hemostatic efficacy was assessed by the investigator as excellent (86%) or good (14%). Inhibitors occurred in three patients of which two were transient (low titer) and one persisted (high titer). These three patients had known risk factors for inhibitor development.
This study demonstrated comparable PK profiles for pediatric patients aged <6 years and aged 6-12 years, and an excellent efficacy and safety profile in this population. The adverse events reported were mostly mild to moderate with inhibitor rates within the expected incidence range.
血浆源性血管性血友病因子/凝血因子VIII（pdVWF/FVIII；VONCENTO，CSL Behring公司）是一种高浓度、小体积、高纯度的浓缩物，具有高水平的血管性血友病因子高分子量多聚体，血管性血友病因子/凝血因子VIII比例约为2.4:1。
本研究（NCT01229007）调查了35例既往接受过治疗（至少20个暴露日[EDs]）的重度A型血友病儿科患者（<12岁）使用pdVWF/FVIII的药代动力学（PK）、疗效和安全性。PK通过单次50 IU FVIII/kg剂量的pdVWF/FVIII进行评估。在按需治疗（n=17）或预防治疗（n=18）期间进行疗效和安全性分析，最长治疗时间为100个EDs，最长研究持续时间为12个月。
<6岁患者和6-12岁患者的PK曲线相似，且正如预期的那样，最年幼的患者清除率增加。按需治疗的患者报告了320次非手术出血（NSB）事件，接受输注的中位数为29.0次（中位剂量34.2 IU FVIII/kg）。研究者评估止血效果在所有病例中均为优/良（24%/76%）。预防治疗组的18例患者发生了173次NSB事件（3例患者发生97次NSB事件[56%]）。5例患者（28%）未发生NSB事件。总体而言，患者接受输注的中位数为92次（中位剂量30.6 IU FVIII/kg）。大多数出血（92%）仅通过一次输注即成功得到控制。研究者评估止血效果为优（86%）或良（14%）。3例患者出现抑制剂，其中2例为短暂性（低滴度），1例持续存在（高滴度）。这3例患者具有已知的抑制剂产生风险因素。
本研究证明<6岁和6-12岁儿科患者的PK曲线具有可比性，且该人群具有优异的疗效和安全性。报告的不良事件大多为轻度至中度，抑制剂发生率在预期范围内。
