Pipe Steven W, Trzaskoma Ben, Minhas Miranda, Lehle Michaela, Ko Richard H, Gao Ling, Mahlangu Johnny, Kempton Christine L, Kessler Craig M, Kruse-Jarres Rebecca
Departments of Pediatrics and Pathology, University of Michigan, Ann Arbor, Michigan, USA.
US Medical Affairs, Genentech Inc, South San Francisco, California, USA.
Res Pract Thromb Haemost. 2023 Feb 8;7(2):100077. doi: 10.1016/j.rpth.2023.100077. eCollection 2023 Feb.
Across the HAVEN clinical trial program, the efficacy of emicizumab has been demonstrated in children, adolescents, and adults with hemophilia A, with or without factor VIII inhibitors. After the 4-week loading dose period, emicizumab concentrations are expected to remain at levels that provide bleed protection throughout the entire dosing interval, regardless of the chosen maintenance dosing regimen, ie, weekly, every 2 weeks, or every 4 weeks.
The objective of this study was to examine the timing of treated bleeds within the dosing intervals for emicizumab administered during the HAVEN 1 to 4 studies.
In this post hoc analysis, we pooled data from all the participants of the HAVEN 1 to 4 studies and analyzed the timing of treated bleeds in relation to the emicizumab dose.
A total of 392 participants were included in this analysis, with a median (range) age of 28.0 years (1.1-77.0 years). Target joints were identified in 237 of 392 (60.5%) participants before the study entry. Overall, 211 of 392 (53.8%) participants experienced 907 treated bleeding events. The total mean (SD) annualized bleeding rate across the 4 studies was 1.6 (5.9). There was no evidence that bleeding events clustered on any 1 particular day in any dosing schedule from HAVEN 1 to 4 ( > .05 for all 3 treatment regimens).
Data from the HAVEN 1 to 4 trials show consistent bleed prevention within the dosing interval, regardless of the dosing regimen chosen. These findings provide further evidence of the sustained efficacy of emicizumab across all approved dosing regimens to reduce bleeding in people with hemophilia A.
在HAVEN临床试验项目中，已证明艾美赛珠单抗对有或无凝血因子VIII抑制剂的血友病A儿童、青少年及成人有效。在4周的负荷剂量期后，无论选择何种维持给药方案，即每周、每2周或每4周给药一次，预计艾美赛珠单抗浓度将维持在整个给药间隔期内提供出血保护的水平。
本研究的目的是检查在HAVEN 1至4研究期间给予的艾美赛珠单抗给药间隔内治疗出血的时间。
在这项事后分析中，我们汇总了HAVEN 1至4研究所有参与者的数据，并分析了与艾美赛珠单抗剂量相关的治疗出血时间。
本分析共纳入392名参与者，中位（范围）年龄为28.0岁（1.1 - 77.0岁）。392名参与者中有237名（60.5%）在研究入组前已确定靶关节。总体而言，392名参与者中有211名（53.8%）经历了907次治疗出血事件。4项研究的总平均（标准差）年化出血率为1.6（5.9）。没有证据表明HAVEN 1至4的任何给药方案中出血事件集中在任何特定的一天（所有3种治疗方案的P>0.05）。
HAVEN 1至4试验的数据表明，无论选择何种给药方案，给药间隔内均能持续预防出血。这些发现进一步证明了艾美赛珠单抗在所有批准的给药方案中对减少血友病A患者出血具有持续疗效。
