Shima Midori, Suzuki Nobuaki, Nishikii Hidekazu, Amano Kagehiro, Ogawa Yoshiyuki, Kobayashi Ryota, Ozaki Ryoto, Yoneyama Koichiro, Mizuno Narumi, Sakaida Emiko, Saito Makoto, Okamura Takashi, Ito Toshihiro, Hattori Norimichi, Higasa Satoshi, Seki Yoshinobu, Nogami Keiji
Thrombosis and Hemostasis Research Center, Nara Medical University, Kashihara, Japan.
Department of Pediatrics, Nara Medical University, Kashihara, Japan.
Thromb Haemost. 2025 May;125(5):449-459. doi: 10.1055/a-2384-3585. Epub 2024 Aug 12.
Primary analysis of the phase III AGEHA study suggested a favorable benefit-risk profile for emicizumab prophylaxis in patients with acquired hemophilia A (PwAHA); however, only patients undergoing immunosuppressive therapy (IST; Cohort 1) were included.To present final analysis results of AGEHA, including data on IST-ineligible patients (Cohort 2) and on long-term prophylaxis with emicizumab.For patients in both Cohorts 1 and 2, emicizumab was administered subcutaneously at 6 mg/kg on Day 1, 3 mg/kg on Day 2, and 1.5 mg/kg once weekly from Day 8 onward.Twelve patients (Cohort 1) and two patients (Cohort 2) were enrolled. Duration of emicizumab treatment was 8 to 639 days (median: 44.5 days) in Cohort 1 and 64 and 450 days in Cohort 2. In both cohorts, no major bleeds were observed after initial emicizumab administration. Six patients started their first rehabilitation sessions during emicizumab treatment and no rehabilitation-related bleeds occurred. Twenty-three surgeries were performed under emicizumab prophylaxis and there were no bleeds related to surgeries. Although asymptomatic deep vein thrombosis was reported in one patient in the primary analysis, no other thrombotic events occurred thereafter. Two patients developed anti-emicizumab antibodies, one of whom showed accelerated emicizumab clearance. Tailored IST approaches (delayed initiation, no use, or reduced dose) were successfully executed in three patients undergoing emicizumab prophylaxis.These results suggest that emicizumab prophylaxis has a favorable benefit-risk profile in PwAHA regardless of eligibility for IST.
III期AGEHA研究的初步分析表明，emicizumab预防治疗对获得性血友病A患者（PwAHA）具有良好的效益风险比；然而，仅纳入了接受免疫抑制治疗（IST；队列1）的患者。现展示AGEHA的最终分析结果，包括IST不适用患者（队列2）以及emicizumab长期预防治疗的数据。对于队列1和队列2的患者，emicizumab于第1天皮下注射6mg/kg，第2天注射3mg/kg，从第8天起每周注射1.5mg/kg。队列1纳入了12例患者，队列2纳入了2例患者。队列1中emicizumab治疗持续时间为8至639天（中位数：44.5天），队列2为64至450天。在两个队列中，首次注射emicizumab后均未观察到严重出血。6例患者在emicizumab治疗期间开始首次康复治疗，未发生与康复相关的出血。在emicizumab预防治疗下进行了23台手术，未发生与手术相关的出血。尽管在初步分析中有1例患者报告了无症状深静脉血栓形成，但此后未发生其他血栓事件。2例患者产生了抗emicizumab抗体，其中1例出现emicizumab清除加速。在3例接受emicizumab预防治疗的患者中成功实施了定制的IST方法（延迟启动、不使用或降低剂量）。这些结果表明，无论是否符合IST标准，emicizumab预防治疗对PwAHA均具有良好的效益风险比。
