Escuriola-Ettingshausen Carmen, Klamroth Robert, Escobar Miguel, Stasyshyn Oleksandra, Tangada Srilatha, Engl Werner, Honauer Ivan, Lee Hye-Youn, Chowdary Pratima, Windyga Jerzy
HZRM Hämophilie-Zentrum Rhein Main, Mörfelden-Walldorf, Germany.
Vivantes Klinikum im Friedrichshain, Berlin, Germany.
Ther Adv Hematol. 2023 Jul 15;14:20406207231178596. doi: 10.1177/20406207231178596. eCollection 2023.
The phase 3, prospective PROPEL study demonstrated that pharmacokinetic (PK)-guided prophylaxis targeting elevated factor VIII (FVIII) troughs in patients with hemophilia A resulted in lower annualized bleeding rates (ABRs) and a higher proportion of patients experiencing zero bleeds in the second 6 months of treatment when targeting a FVIII trough of 8-12% 1-3%.
To investigate the benefit of PK-guided prophylaxis with rurioctocog alfa pegol targeting two FVIII trough levels in specific patient subgroups in a analysis using data from PROPEL.
This is a analysis of data from the PROPEL study. The design and primary outcomes of the prospective, randomized PROPEL study (NCT02585960) have been reported previously.
This analysis reports data stratified by FVIII half-life (), hemophilic arthropathy status, number of target joints at screening, previous treatment regimen, and ABR range in the 12 months before study entry.
Targeting an elevated FVIII trough of 8-12% was associated with higher average FVIII levels over time, regardless of FVIII at baseline. The decrease in total ABR between the 8-12% and 1-3% arms was greatest in patients with a FVIII of 6 to <12 h (0.7 3.5); a higher number of target joints, that is, at least four target joints, at baseline (0.2 1.6); the presence of arthropathy (0.1 1.7); and those previously treated on-demand (0.3 1.8).
These results support the feasibility of targeting elevated FVIII levels using personalized rurioctocog alfa pegol prophylaxis. These benefits may be especially important in patients with a short FVIII and those receiving standard prophylaxis with frequent breakthrough bleeds, arthropathy, and target joints.
ClinicalTrials.gov Identifier: NCT02585960; https://clinicaltrials.gov/ct2/show/NCT02585960.
3期前瞻性PROPEL研究表明，在A型血友病患者中，针对因子VIII（FVIII）谷值升高进行药代动力学（PK）引导的预防，当将FVIII谷值目标设定为8%-12%而非1%-3%时，年化出血率（ABR）更低，且在治疗的第二个6个月中零出血的患者比例更高。
利用PROPEL研究的数据，在一项亚组分析中，探讨聚乙二醇重组人凝血因子VIII（rurioctocog alfa pegol）针对两个FVIII谷值水平进行PK引导的预防在特定患者亚组中的益处。
这是一项对PROPEL研究数据的亚组分析。前瞻性随机PROPEL研究（NCT02585960）的设计和主要结局此前已报道。
本亚组分析报告了按FVIII半衰期、血友病关节病状态、筛查时的目标关节数量、既往治疗方案以及研究入组前12个月的ABR范围分层的数据。
无论基线时的FVIII半衰期如何，将升高的FVIII谷值目标设定为8%-12%与随时间推移更高的平均FVIII水平相关。在FVIII半衰期为6至<12小时的患者中（0.7对3.5）；基线时目标关节数量较多，即至少四个目标关节的患者中（0.2对1.6）；存在关节病的患者中（0.1对1.7）；以及既往接受按需治疗的患者中（0.3对1.8），8%-12%组与1%-3%组之间总ABR的降低最为显著。
这些结果支持使用个性化的聚乙二醇重组人凝血因子VIII预防方案将FVIII水平升高作为目标的可行性。这些益处对于FVIII半衰期短以及接受标准预防但频繁出现突破性出血、关节病和目标关节的患者可能尤为重要。
ClinicalTrials.gov标识符：NCT02585960；https://clinicaltrials.gov/ct2/show/NCT02585960
