Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
J Thromb Haemost. 2011 Nov;9(11):2180-92. doi: 10.1111/j.1538-7836.2011.04472.x.
As a result of the infrequency of inhibitors in previously treated patients (PTPs) with hemophilia A and the small size of available clinical studies, the immunogenicity of factor (F)VIII products has been difficult to assess.
A meta-analysis of prospective clinical studies was conducted to test the hypothesis that de novo inhibitor incidence differs between PTPs receiving full-length recombinant FVIII (FL-rFVIII) and B-domain deleted recombinant FVIII (BDD-rFVIII).
Prospective studies with data on inhibitors in PTPs receiving FL-rFVIII or BDD-rFVIII were sought using systematic methods including bibliographic database searches. Data were secured from published study reports and inquiries to investigators. Between-group differences in inhibitor incidence rates were evaluated using mixed effects Cox regression.
Twenty-nine studies with 3012 total PTPs were included. Patients were at risk of de novo inhibitor development for a median of 79 exposure days. A total of 35 de novo inhibitors were observed. The cumulative hazard for all de novo inhibitors was 1.25% with a 95% confidence interval (CI) of 0.63-1.88%. The corresponding rate for high-titer de novo inhibitors [> 5 Bethesda units (BU)] was 0.29% (CI, 0.01-0.57%). Exposure to BDD-rFVIII was associated with an increased risk of all de novo inhibitors (hazard ratio, 7.26; CI, 2.12-24.9; P = 0.0016) and of high-titer de novo inhibitors (hazard ratio, 10.8; CI, 2.17-53.7; P = 0.0037), compared with FL-rFVIII.
This meta-analysis of prospective clinical studies suggests that recombinant FVIII products may differ in immunogenicity.
由于先前接受过治疗的血友病 A 患者（PTP）中抑制剂的出现频率较低，并且可用的临床研究规模较小，因此评估因子（F）VIII 产品的免疫原性一直具有挑战性。
对前瞻性临床研究进行荟萃分析，以检验以下假设：接受全长重组 FVIII（FL-rFVIII）和 B 结构域缺失重组 FVIII（BDD-rFVIII）治疗的 PTP 中，新出现抑制剂的发生率不同。
使用系统方法（包括文献数据库搜索）寻找接受 FL-rFVIII 或 BDD-rFVIII 治疗的 PTP 中抑制剂的前瞻性研究。从已发表的研究报告和对研究者的查询中获取数据。使用混合效应 Cox 回归评估抑制剂发生率的组间差异。
共纳入 29 项研究，总计 3012 名 PTP 患者。患者有发生新抑制剂的风险，中位暴露时间为 79 天。共观察到 35 例新抑制剂。所有新抑制剂的累积风险为 1.25%，95%置信区间（CI）为 0.63-1.88%。高滴度新抑制剂（>5 贝塔单位（BU））的相应发生率为 0.29%（CI，0.01-0.57%）。与 FL-rFVIII 相比，BDD-rFVIII 的暴露与所有新抑制剂（风险比，7.26；CI，2.12-24.9；P=0.0016）和高滴度新抑制剂（风险比，10.8；CI，2.17-53.7；P=0.0037）的风险增加相关。
本前瞻性临床研究荟萃分析表明，重组 FVIII 产品的免疫原性可能存在差异。
