Iorio A, Krishnan S, Myrén K J, Lethagen S, McCormick N, Yermakov S, Karner P
McMaster University, Hamilton, ON, Canada.
Biogen Hemophilia, Cambridge, MA, USA.
Haemophilia. 2017 May;23(3):408-416. doi: 10.1111/hae.13160. Epub 2017 Feb 24.
Recombinant factor VIII (rFVIII) products with extended half-lives have the potential to improve adherence and outcomes in haemophilia beyond the results obtained with conventional rFVIII products.
In the absence of head-to-head comparisons, annualized bleed rates (ABRs) and weekly factor consumption with rFVIII Fc fusion protein (rFVIIIFc) and conventional rFVIII products were indirectly compared using studies of continuous prophylaxis.
A systematic literature review was conducted to identify studies of rFVIII products for comparison with rFVIIIFc in the continuous prophylactic treatment of previously treated adolescents and adults with moderate and severe haemophilia A. Mean ABRs were compared between rFVIIIFc and individual rFVIII studies and between rFVIIIFc and a pooled measure for rFVIII estimated by meta-analysis. Comparisons of factor consumption were based on mean or median weekly factor consumption.
Results from seven studies of conventional rFVIII products (injections 2-4 times week ) were compared with rFVIIIFc (injections 1.4-2.4 times week ). The pooled mean ABR for rFVIII products was significantly higher compared with rFVIIIFc (difference = 2.0; P = 0.007). Compared with most rFVIII studies, the reported weekly factor consumption was lower with rFVIIIFc [mean differences = 15.5-21.8 IU kg week (17-26%); median differences = 12.7-29.8 IU kg week (16-37%)]. In one comparison, mean weekly factor consumption with rFVIII was significantly lower but mean ABR was significantly higher than rFVIIIFc.
Prophylaxis with rFVIIIFc may be associated with improved bleeding rates and lower weekly factor consumption than more frequently injected rFVIII products. Relative to rFVIII products with similar bleeding rates, results indicate that rFVIIIFc is associated with reduced weekly factor consumption while requiring fewer prescribed injections.
半衰期延长的重组凝血因子VIII（rFVIII）产品有可能改善血友病患者的依从性并提高治疗效果，优于传统rFVIII产品所取得的结果。
在缺乏头对头比较的情况下，通过连续预防研究间接比较rFVIII Fc融合蛋白（rFVIIIFc）和传统rFVIII产品的年化出血率（ABR）及每周凝血因子消耗量。
进行了一项系统的文献综述，以确定rFVIII产品在连续预防性治疗既往接受过治疗的中度和重度甲型血友病青少年及成人中的研究，用于与rFVIIIFc进行比较。比较了rFVIIIFc与各个rFVIII研究之间的平均ABR，以及rFVIIIFc与通过荟萃分析估计的rFVIII汇总指标之间的平均ABR。凝血因子消耗量的比较基于每周平均或中位数凝血因子消耗量。
将七项传统rFVIII产品（每周注射2 - 4次）的研究结果与rFVIIIFc（每周注射1.4 - 2.4次）进行了比较。rFVIII产品的汇总平均ABR显著高于rFVIIIFc（差异 = 2.0；P = 0.007）。与大多数rFVIII研究相比，rFVIIIFc报告的每周凝血因子消耗量更低[平均差异 = 15.5 - 21.8 IU/kg/周（17 - 26%）；中位数差异 = 12.7 - 29.8 IU/kg/周（16 - 37%）]。在一项比较中，rFVIII的每周平均凝血因子消耗量显著更低，但平均ABR显著高于rFVIIIFc。
与更频繁注射的rFVIII产品相比，使用rFVIIIFc进行预防可能与出血率改善和每周凝血因子消耗量降低相关。相对于具有相似出血率的rFVIII产品，结果表明rFVIIIFc与每周凝血因子消耗量减少相关，同时所需的处方注射次数更少。
