Department for Internal Medicine, Vascular Medicine and Haemostaseology, Vivantes Klinikum Friedrichshain, Berlin, Germany.
Department of Hemostasis Disorders and Internal Medicine, Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
Blood. 2021 Apr 1;137(13):1818-1827. doi: 10.1182/blood.2020005673.
Rurioctocog alfa pegol prophylaxis targeting factor VIII (FVIII) troughs ≥1% has shown to be efficacious with an acceptable safety profile in people with hemophilia A (PwHA). The PROPEL trial compared safety and efficacy of 2 target FVIII troughs in PwHA aged 12 to 65 years, with severe disease, annualized bleeding rate ≥2, and previous FVIII treatment. PwHA were randomized to 12 months' pharmacokinetic (PK)-guided rurioctocog alfa pegol prophylaxis targeting FVIII troughs of 1% to 3% (reference arm) or 8% to 12% (elevated arm); first 6 months was treatment-adjustment period. The primary endpoint was absence of bleeds during the second 6 months, analyzed using multiple imputations (full analysis set [FAS]). In the 1% to 3% and 8% to 12% arms, respectively, point estimates (95% confidence interval) of proportions of PwHA with zero total bleeds were 42% (29% to 55%) and 62% (49% to 75%) in FAS (N = 115; P = .055) and 40% (27% to 55%) and 67% (52% to 81%) in per-protocol analysis set (N = 95; P = .015). Dosing frequency and consumption varied in each arm. Adverse events (AEs) occurred in 70/115 (60.9%) PwHA; serious AEs in 7/115 (6%) PwHA, including 1 treatment-related in 8% to 12% arm (transient anti-FVIII inhibitor). There were no deaths, serious thrombotic events, or AE-related discontinuations. PK-guided prophylaxis was achievable and efficacious in both arms. No new safety signals were observed in the 8% to 12% arm. These results demonstrate elevated FVIII troughs can increase the proportion of PwHA with zero bleeds and emphasize the importance of personalized treatment. This trial was registered at www.clinicaltrials.gov as #NCT02585960.
聚乙二醇化奥克洛单抗预防治疗针对因子 VIII（FVIII）谷浓度≥1%，在 A 型血友病患者（PwHA）中显示出疗效和可接受的安全性。PROPEL 试验比较了 12 至 65 岁、疾病严重程度高、年化出血率≥2、且有 FVIII 治疗史的 PwHA 接受 2 种目标 FVIII 谷浓度的安全性和疗效，患者随机接受 12 个月的药代动力学（PK）指导的聚乙二醇化奥克洛单抗预防治疗，目标 FVIII 谷浓度分别为 1%至 3%（参照组）或 8%至 12%（升高组）；前 6 个月为治疗调整期。主要终点为第 2 个 6 个月内无出血，采用多重插补（全分析集[FAS]）进行分析。参照组和升高组分别有 42%（29%至 55%）和 62%（49%至 75%）的 PwHA 无总出血（FAS，N=115；P=0.055），分别有 40%（27%至 55%）和 67%（52%至 81%）的 PwHA 无出血（符合方案分析集，N=95；P=0.015）。每个组的给药频率和消耗量不同。115 例 PwHA 中有 70 例（60.9%）发生不良事件（AE）；7 例（6%）发生严重 AE，包括升高组的 1 例（一过性抗 FVIII 抑制剂）与治疗相关的 AE。无死亡、严重血栓事件或 AE 相关停药。在两个组中，PK 指导的预防治疗是可行和有效的。升高组未观察到新的安全性信号。这些结果表明，升高 FVIII 谷浓度可以增加无出血 PwHA 的比例，并强调了个体化治疗的重要性。该试验在 www.clinicaltrials.gov 注册，编号为#NCT02585960。
