全长无血浆蛋白重组凝血因子VIII产品BAY 81-8973的预防性治疗与按需治疗对比：一项随机试验（LEOPOLD II）的结果
Prophylaxis vs. on-demand treatment with BAY 81-8973, a full-length plasma protein-free recombinant factor VIII product: results from a randomized trial (LEOPOLD II).
作者信息
Kavakli K, Yang R, Rusen L, Beckmann H, Tseneklidou-Stoeter D, Maas Enriquez M
机构信息
Ege University Children’s Hospital, Izmir, Turkey.
出版信息
J Thromb Haemost. 2015 Mar;13(3):360-9. doi: 10.1111/jth.12828.
BACKGROUND
BAY 81-8973 is a new full-length human recombinant factor VIII product manufactured with technologies to improve consistency in glycosylation and expression to optimize clinical performance.
OBJECTIVES
To demonstrate superiority of prophylaxis vs. on demand therapy with BAY 81-8973 in patients with severe hemophilia A.
PATIENTS/METHODS: In this multinational,randomized, open-label crossover study (LEOPOLD II;ClinicalTrials.gov identifier: NCT01233258), males aged 12–65 years with severe hemophilia A were randomized to twice-weekly prophylaxis (20-30 IU kg(-1)), 3-times-weekly prophylaxis (30-40 IU kg(-1)), or on-demand treatment with BAY 81-8973. Potency labeling for BAY 81-8973 was based on the chromogenic substrate assay or adjusted to the one-stage assay. Primary efficacy endpoint was annualized number of all bleeds (ABR). Adverse events (AEs)and immunogenicity were also assessed.
RESULTS
Eighty patients (on demand, n = 21; twice-weekly prophylaxis, n = 28; 3-times-weekly prophylaxis, n = 31) were treated and analyzed. Mean ± SD ABR was significantly lower with prophylaxis (twice-weekly, 5.7 ± 7.2; 3-times-weekly, 4.3 ± 6.5; combined, 4.9 ± 6.8) vs. on-demand treatment (57.7 ± 24.6; P < 0.0001, ANOVA). Median ABR was reduced by 97% with prophylaxis (twice-weekly, 4.0;3-times-weekly, 2.0; combined, 2.0) vs. on-demand treatment (60.0). Median ABR was higher with twice-weekly vs. 3-times-weekly prophylaxis during the first 6-month treatment period (4.1 vs. 2.0) but was comparable in the second 6-month period (1.1 vs. 2.0). Few patients reported treatment-related AEs (4%); no treatment-related serious AEs or inhibitors were reported.
CONCLUSIONS
Twice weekly or 3-times-weekly prophylaxis with BAY 81-8973 reduced median ABR by 97% compared with on-demand therapy, confirming the superiority of prophylaxis. Treatment with BAY 81-8973 was well tolerated.
背景
BAY 81-8973是一种新型全长人重组凝血因子VIII产品，采用了优化糖基化和表达一致性的技术以优化临床性能。
目的
在重度A型血友病患者中证明BAY 81-8973预防治疗对比按需治疗的优越性。
患者/方法：在这项多国、随机、开放标签交叉研究（LEOPOLD II；ClinicalTrials.gov标识符：NCT01233258）中，年龄在12至65岁的重度A型血友病男性被随机分为接受每周两次预防治疗（20 - 30 IU kg⁻¹）、每周三次预防治疗（30 - 40 IU kg⁻¹）或使用BAY 81-8973进行按需治疗。BAY 81-8973的效价标记基于发色底物测定法或根据一步测定法进行调整。主要疗效终点是年化出血次数（ABR）。还评估了不良事件（AE）和免疫原性。
结果
80名患者（按需治疗组，n = 21；每周两次预防治疗组，n = 28；每周三次预防治疗组，n = 31）接受治疗并进行分析。与按需治疗（57.7 ± 24.6）相比，预防治疗组（每周两次，5.7 ± 7.2；每周三次，4.3 ± 6.5；合并，4.9 ± 6.8）的平均±标准差ABR显著更低（方差分析，P < 0.0001）。与按需治疗（60.0）相比，预防治疗组（每周两次，4.0；每周三次，2.0；合并，2.0）的ABR中位数降低了97%。在治疗的前六个月期间，每周两次预防治疗的ABR中位数高于每周三次预防治疗（4.1对2.0），但在后六个月期间相当（1.1对2.0）。很少有患者报告与治疗相关的不良事件（4%）；未报告与治疗相关的严重不良事件或抑制剂。
结论
与按需治疗相比，每周两次或三次使用BAY 81-8973进行预防治疗可使ABR中位数降低97%，证实了预防治疗的优越性。BAY 81-8973治疗耐受性良好。
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