重组凝血因子VIII/凝血因子IX Fc在A型/ B型血友病中的真实世界应用及疗效：德国一项为期24个月的前瞻性非干预性PREVENT研究的最终数据
Real-world usage and effectiveness of recombinant factor VIII/factor IX Fc in hemophilia A/B: final data from the 24-month, prospective, noninterventional PREVENT study in Germany.
作者信息
Bidlingmaier Christoph, Heller Christine, Langer Florian, Miesbach Wolfgang, Scholz Ute, Oldenburg Johannes, Nüesch Eveline, Palmborg Helena, Santagostino Elena, Tiede Andreas
机构信息
Department of Pediatrics, Dr. von Hauner Children's Hospital, Pediatric Hemophilia Center, LMU Munich, Munich, Germany.
Department of Pediatric Haemostaseology, University Hospital of Frankfurt, Frankfurt, Germany.
出版信息
Res Pract Thromb Haemost. 2024 Jun 21;8(5):102482. doi: 10.1016/j.rpth.2024.102482. eCollection 2024 Jul.
BACKGROUND
Real-world experience with efmoroctocog alfa (a recombinant factor [F]VIII Fc fusion protein [rFVIIIFc]) and eftrenonacog alfa (a recombinant factor IX Fc fusion protein [rFIXFc]) is needed to bridge evidence gaps.
OBJECTIVES
To describe rFVIIIFc/rFIXFc usage and effectiveness over a 24-month prospective period.
METHODS
PREVENT (NCT03055611), a noninterventional study across 25 German hemophilia treatment centers, enrolled previously treated persons with hemophilia A and B (all ages/severities) on individualized rFVIIIFc/rFIXFc prophylaxis before/at enrollment. Primary endpoints included annualized bleeding rate (ABR), injection frequency (IF), and factor consumption (FC). Additionally, up to 12 months of retrospective FVIII/FIX data were collected. Physician and patient satisfaction, and safety outcomes were also assessed.
RESULTS
Overall, 150 patients received ≥1 rFVIIIFc dose and 47 patients received ≥1 rFIXFc dose, with median prospective follow-up of 20.6 and 21.0 months, respectively. rFVIIIFc/rFIXFc demonstrated low median ABR (0.5/1.7), annualized IF (121.8/52.2 injections/y), and FC (4611.7/2423.9 IU/kg) in line with product labels. Compared with previous FVIII/FIX, there was a 56.0% reduction in ABR for rFVIIIFc (rate ratio, 0.44; 95% CI, 0.31-0.64), with no change for rFIXFc (rate ratio, 0.93; 95% CI, 0.66-1.31); rFVIIIFc/rFIXFc reduced annualized IF (rFVIIIFc, mean difference, -31.7; 95% CI, -40.3 to -23.1; rFIXFc, mean difference, -37.3; 95% CI, -46.9 to -27.8), while FC remained stable (rFVIIIFc, +374.1; 95% CI, +46.8 to +701.3; rFIXFc, +503.9; 95% CI, +95.4 to +912.4). Most physicians and patients were satisfied or highly satisfied with rFVIIIFc/rFIXFc. rFVIIIFc/rFIXFc were well tolerated, with no inhibitor development or treatment-related serious adverse events.
CONCLUSION
Real-world PREVENT data complement phase 3 trials and show that individualized rFVIIIFc/rFIXFc prophylaxis provided stable bleed protection with low IF and maintained FC. Compared with previous FVIII, ABR was considerably reduced with rFVIIIFc, with stable annualized FC. For rFIXFc, bleed protection was maintained vs previous FIX while reducing annualized IF.
背景
需要依诺凝血因子α（一种重组因子[F]VIII Fc融合蛋白[rFVIIIFc]）和依曲非巴凝血因子α（一种重组因子IX Fc融合蛋白[rFIXFc]）的真实世界经验来填补证据空白。
目的
描述24个月前瞻性研究期间rFVIIIFc/rFIXFc的使用情况和有效性。
方法
PREVENT（NCT03055611）是一项在25个德国血友病治疗中心开展的非干预性研究，纳入了之前接受过治疗的血友病A和B患者（所有年龄/严重程度），在入组前/入组时接受个体化rFVIIIFc/rFIXFc预防治疗。主要终点包括年化出血率（ABR）、注射频率（IF）和因子消耗量（FC）。此外，收集了长达12个月的回顾性FVIII/FIX数据。还评估了医生和患者的满意度以及安全性结果。
结果
总体而言，150例患者接受了≥1剂rFVIIIFc，47例患者接受了≥1剂rFIXFc，rFVIIIFc和rFIXFc的前瞻性中位随访时间分别为20.6个月和21.0个月。rFVIIIFc/rFIXFc的中位ABR（0.5/1.7）、年化IF（121.8/52.2次注射/年）和FC（4611.7/2423.9 IU/kg）较低，与产品标签一致。与之前的FVIII/FIX相比，rFVIIIFc的ABR降低了56.0%（率比，0.44；95%CI，0.31 - 0.64），rFIXFc无变化（率比，0.93；95%CI，0.66 - 1.31）；rFVIIIFc/rFIXFc降低了年化IF（rFVIIIFc，平均差值，-31.7；95%CI，-40.3至-23.1；rFIXFc，平均差值，-37.3；95%CI，-46.9至-27.8），而FC保持稳定（rFVIIIFc，+374.1；95%CI，+46.8至+701.3；rFIXFc，+503.9；95%CI，+95.4至+912.4）。大多数医生和患者对rFVIIIFc/rFIXFc感到满意或非常满意。rFVIIIFc/rFIXFc耐受性良好，未出现抑制剂产生或与治疗相关的严重不良事件。
结论
PREVENT研究的真实世界数据补充了3期试验，表明个体化rFVIIIFc/rFIXFc预防治疗以低IF提供了稳定的出血保护并维持了FC。与之前的FVIII相比，rFVIIIFc显著降低了ABR，年化FC保持稳定。对于rFIXFc，与之前的FIX相比，在降低年化IF的同时维持了出血保护。
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