Carmen Escuriola-Ettingshausen, Robert Klamroth, Miguel Escobar, Oleksandra Stasyshyn, Srilatha Tangada, Werner Engl, Ivan Honauer, Hye-Youn Lee, Pratima Chowdary, Jerzy Windyga
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The design and primary outcomes of the prospective, randomized PROPEL study (NCT02585960) have been reported previously.</p><p><strong>Methods: </strong>This <i>post hoc</i> analysis reports data stratified by FVIII half-life (<i>t</i><sub>1/2</sub>), hemophilic arthropathy status, number of target joints at screening, previous treatment regimen, and ABR range in the 12 months before study entry.</p><p><strong>Results: </strong>Targeting an elevated FVIII trough of 8-12% was associated with higher average FVIII levels over time, regardless of FVIII <i>t</i><sub>1/2</sub> at baseline. The decrease in total ABR between the 8-12% and 1-3% arms was greatest in patients with a FVIII <i>t</i><sub>1/2</sub> of 6 to <12 h (0.7 <i>versus</i> 3.5); a higher number of target joints, that is, at least four target joints, at baseline (0.2 <i>versus</i> 1.6); the presence of arthropathy (0.1 <i>versus</i> 1.7); and those previously treated on-demand (0.3 <i>versus</i> 1.8).</p><p><strong>Conclusion: </strong>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 <i>t</i><sub>1/2</sub> and those receiving standard prophylaxis with frequent breakthrough bleeds, arthropathy, and target joints.</p><p><strong>Registration: </strong>ClinicalTrials.gov Identifier: NCT02585960; https://clinicaltrials.gov/ct2/show/NCT02585960.</p>","PeriodicalId":23048,"journal":{"name":"Therapeutic Advances in Hematology","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f7/80/10.1177_20406207231178596.PMC10350756.pdf","citationCount":"0","resultStr":"{\"title\":\"Targeting an elevated FVIII level using personalized rurioctocog alfa pegol prophylaxis in specific patient populations with hemophilia A: <i>post hoc</i> subanalysis of the randomized, phase 3 PROPEL study.\",\"authors\":\"Carmen Escuriola-Ettingshausen, Robert Klamroth, Miguel Escobar, Oleksandra Stasyshyn, Srilatha Tangada, Werner Engl, Ivan Honauer, Hye-Youn Lee, Pratima Chowdary, Jerzy Windyga\",\"doi\":\"10.1177/20406207231178596\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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% <i>versus</i> 1-3%.</p><p><strong>Objective: </strong>To investigate the benefit of PK-guided prophylaxis with rurioctocog alfa pegol targeting two FVIII trough levels in specific patient subgroups in a <i>post hoc</i> analysis using data from PROPEL.</p><p><strong>Design: </strong>This is a <i>post hoc</i> analysis of data from the PROPEL study. The design and primary outcomes of the prospective, randomized PROPEL study (NCT02585960) have been reported previously.</p><p><strong>Methods: </strong>This <i>post hoc</i> analysis reports data stratified by FVIII half-life (<i>t</i><sub>1/2</sub>), hemophilic arthropathy status, number of target joints at screening, previous treatment regimen, and ABR range in the 12 months before study entry.</p><p><strong>Results: </strong>Targeting an elevated FVIII trough of 8-12% was associated with higher average FVIII levels over time, regardless of FVIII <i>t</i><sub>1/2</sub> at baseline. 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引用次数: 0
摘要
背景:3期前瞻性PROPEL研究表明，针对A型血友病患者的FVIII升高谷的药代动力学(PK)指导预防导致较低的年化出血率(abr)，并且当FVIII谷为8-12%而不是1-3%时，治疗后6个月零出血的患者比例更高。目的:通过对PROPEL数据的事后分析，探讨在特定患者亚组中，ruurioctocog alfa pegol靶向两个FVIII谷水平的pk指导预防的益处。设计:这是对PROPEL研究数据的事后分析。前瞻性、随机的PROPEL研究(NCT02585960)的设计和主要结果此前已有报道。方法:本回顾性分析报告了研究开始前12个月FVIII半衰期(t1/2)、血友病关节病状态、筛查目标关节数量、既往治疗方案和ABR范围的数据分层。结果:无论基线FVIII t1/2如何，将FVIII波谷升高8-12%作为目标，随着时间的推移，平均FVIII水平都会升高。8-12%组和1-3%组总ABR的下降在FVIII t1/2(6比3.5)的患者中最大;基线时目标关节数量较多，即至少有4个目标关节(0.2 vs 1.6);存在关节病变(0.1对1.7);而先前按需治疗的患者(0.3 vs 1.8)。结论:这些结果支持了个体化预防治疗FVIII水平升高的可行性。这些益处对于FVIII短t1/2的患者和那些接受标准预防并经常出现突破性出血、关节病变和靶关节的患者尤其重要。注册:ClinicalTrials.gov标识符:NCT02585960;https://clinicaltrials.gov/ct2/show/NCT02585960。
Targeting an elevated FVIII level using personalized rurioctocog alfa pegol prophylaxis in specific patient populations with hemophilia A: post hoc subanalysis of the randomized, phase 3 PROPEL study.
Background: 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% versus 1-3%.
Objective: To investigate the benefit of PK-guided prophylaxis with rurioctocog alfa pegol targeting two FVIII trough levels in specific patient subgroups in a post hoc analysis using data from PROPEL.
Design: This is a post hoc analysis of data from the PROPEL study. The design and primary outcomes of the prospective, randomized PROPEL study (NCT02585960) have been reported previously.
Methods: This post hoc analysis reports data stratified by FVIII half-life (t1/2), hemophilic arthropathy status, number of target joints at screening, previous treatment regimen, and ABR range in the 12 months before study entry.
Results: Targeting an elevated FVIII trough of 8-12% was associated with higher average FVIII levels over time, regardless of FVIII t1/2 at baseline. The decrease in total ABR between the 8-12% and 1-3% arms was greatest in patients with a FVIII t1/2 of 6 to <12 h (0.7 versus 3.5); a higher number of target joints, that is, at least four target joints, at baseline (0.2 versus 1.6); the presence of arthropathy (0.1 versus 1.7); and those previously treated on-demand (0.3 versus 1.8).
Conclusion: 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 t1/2 and those receiving standard prophylaxis with frequent breakthrough bleeds, arthropathy, and target joints.
期刊介绍：
Therapeutic Advances in Hematology delivers the highest quality peer-reviewed articles, reviews, and scholarly comment on pioneering efforts and innovative studies across all areas of hematology. The journal has a strong clinical and pharmacological focus and is aimed at clinicians and researchers in hematology, providing a forum in print and online for publishing the highest quality articles in this area.
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