Hemophilia Comprehensive Care Center, Faculty of Health Sciences, Charlotte Maxeke Johannesburg Academic Hospital, University of the Witwatersrand, and National Health Laboratory Service, Johannesburg, South Africa.
INIBIC-C.H.U. A Coruña, Complexo Hospitalario Universitario, Hospital Materno Infantil, A Coruña, Spain.
Eur J Haematol. 2020 Jun;104(6):594-601. doi: 10.1111/ejh.13402. Epub 2020 Mar 23.
BAY 81-8973 (Kovaltry ), a full-length, unmodified, recombinant human factor VIII, provided excellent bleeding control for patients with haemophilia A in the pivotal 1-year LEOPOLD I trial. The LEOPOLD I extension evaluated long-term efficacy and safety of BAY 81-8973 prophylaxis.
After completing LEOPOLD I, patients continued receiving 20-50 IU/kg BAY 81-8973 two- or three-times weekly in the extension. Outcomes included annualised bleeding rate (ABR) and haemostasis during surgery.
Fifty-five patients aged 12-65 years participated in the extension. Median (range) exposure days during the 2-year total study period was 309 (115-355). No patient switched regimens. Median (Q1; Q3) ABR for all bleeds was 2.0 (1.0; 6.1) during the pivotal study, 2.0 (0.0; 5.2) during the extension, and 2.0 (0.5; 5.5) combined. The proportion of joint bleeds affecting target joints decreased (pivotal study: 90.9%, extension: 60.0%). Haemostasis was assessed as excellent/good in all five major surgeries. One serious adverse event (myocardial infarction) occurred in a patient with cardiovascular risk factors. No patients developed inhibitors.
BAY 81-8973 prophylaxis efficacy outcomes in the pivotal study were maintained or, in the case of joint protection, improved during the extension, with a safety and tolerability profile consistent with previous experience.
BAY 81-8973（Kovaltry）是一种全长、未经修饰的重组人凝血因子 VIII，在关键的 1 年 LEOPOLD I 试验中为 A 型血友病患者提供了出色的出血控制效果。LEOPOLD I 扩展研究评估了 BAY 81-8973预防治疗的长期疗效和安全性。
完成 LEOPOLD I 后，患者在扩展研究中继续接受 20-50IU/kg BAY 81-8973 每周两次或三次的预防治疗。结果包括年化出血率（ABR）和手术期间的止血效果。
55 名年龄在 12-65 岁的患者参与了扩展研究。在为期 2 年的总研究期间，中位数（范围）暴露天数为 309（115-355）。无患者转换治疗方案。所有出血的中位数（Q1；Q3）ABR 在关键研究中为 2.0（1.0；6.1），在扩展研究中为 2.0（0.0；5.2），两者合并为 2.0（0.5；5.5）。影响目标关节的关节出血比例下降（关键研究：90.9%，扩展研究：60.0%）。所有 5 项主要手术的止血效果均评估为优秀/良好。一名患有心血管危险因素的患者发生了 1 例严重不良事件（心肌梗死）。无患者产生抑制剂。
在扩展研究中，关键研究中 BAY 81-8973 预防治疗的疗效结果得以维持，或者在关节保护方面得到了改善，安全性和耐受性与之前的经验一致。
