艾美赛珠单抗在中国儿童甲型血友病患者中的真实世界应用：来自一家综合护理中心的回顾性数据

Real-world use of emicizumab in Chinese children with hemophilia A: Retrospective data from a comprehensive care center.

作者信息

Mao Qianqian, Chen Zhenping, Liu Guoqing, Li Gang, Zhen Yingzi, Cheng Xiaoling, Li Zekun, Yao Wanru, Ai Di, Li Zhengping, Wang Nan, Poon Man-Chiu, Wu Runhui

机构信息

Hematology Department, Hemophilia Comprehensive Care Center, Hematology Center, Beijing Key Laboratory of Pediatric Hematology-Oncology, Key Laboratory of Major Diseases in Children, National Center for Children's Health National Key Discipline of Pediatrics (Capital Medical University), Ministry of Education, Beijing Children's Hospital, Capital Medical University Beijing China.

Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology-Oncology, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, National Center for Children's Health National Key Discipline of Pediatrics (Capital Medical University), Beijing Children's Hospital, Capital Medical University Beijing China.

出版信息

Pediatr Investig. 2024 Jul 22;8(4):244-252. doi: 10.1002/ped4.12439. eCollection 2024 Dec.

DOI:10.1002/ped4.12439

PMID:39720280

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11664537/

Abstract

IMPORTANCE

Emicizumab (EMI) is efficacious and safe for hemophilia A (HA) prophylaxis. However, its high cost poses a challenge in China.

OBJECTIVE

To explore the possibility of using reduced-dosage EMI in Chinese HA children.

METHODS

We conducted a retrospective study for HA children in our Comprehensive Care Center. Data were collected pre- and post-EMI treatment to evaluate bleeding rates. Laboratory analyses included factor VIII (FVIII)-like activity and EMI concentration measurements.

RESULTS

Thirty-four HA children receiving EMI prophylaxis for a median (range) 24.5 (2.5-47.9) months by June 2023. Of these, 25 (73.5%) were under 3 years of age, 26 (76.5%) had severe hemophilia and 12 (35.3%) were minimally treated or previously untreated patients. Thirty-one (91.2%) of the 34 patients received reduced-dosage EMI for economic reasons. EMI concentration and FVIII-like activity measured showed a strong correlation. Overall, while on EMI, their annual treated bleeding rate (ATBR) and annual bleeding rate (ABR) decreased significantly (2-0) while their zero-bleeding rate (ZBR) increased significantly (11.5%-65.4%). After 6 months of EMI, there was no significant difference in ATBR and ABR among various maintenance dosages. However, ZBR was significantly lower in dosages under 4 mg/kg ( = 0.0156). Receiver operator characteristic curves suggested the following cutoff values for zero bleeding: EMI 4-weekly maintenance dosage 3.8 mg/kg, EMI concentration 48.1 μg/mL, and FVIII-like activity 15.4 IU/dL.

INTERPRETATION

We showed EMI effectively prevented bleeding even at reduced dosages. However, the bleeding risk may be higher with EMI 4-weekly maintenance dosage <3.8 mg/kg, EMI concentration <48.1 μg/mL, and FVIII-like activity <15.4 IU/dL for zero bleeding. It is important that dosage reduction be done rationally. Dosage tailoring is possible.

摘要

重要性

艾美赛珠单抗（EMI）用于A型血友病（HA）预防有效且安全。然而，其高昂的成本给中国带来了挑战。

目的

探讨在中国HA患儿中使用低剂量EMI的可能性。

方法

我们对综合护理中心的HA患儿进行了一项回顾性研究。在EMI治疗前后收集数据以评估出血率。实验室分析包括因子VIII（FVIII）样活性和EMI浓度测量。

结果

截至2023年6月，34名接受EMI预防的HA患儿，中位（范围）治疗时间为24.5（2.5 - 47.9）个月。其中，25名（73.5%）年龄在3岁以下，26名（76.5%）患有重度血友病，12名（35.3%）为轻度治疗或既往未治疗患者。34名患者中有31名（91.2%）因经济原因接受了低剂量EMI。测量的EMI浓度和FVIII样活性显示出很强的相关性。总体而言，在使用EMI期间，他们的年治疗出血率（ATBR）和年出血率（ABR）显著下降（从2次降至0次），而零出血率（ZBR）显著上升（从11.5%升至65.4%）。EMI治疗6个月后，不同维持剂量之间的ATBR和ABR无显著差异。然而，4mg/kg以下剂量的ZBR显著较低（P = 0.0156）。受试者工作特征曲线表明零出血的以下临界值：EMI每4周维持剂量3.8mg/kg、EMI浓度48.1μg/mL和FVIII样活性15.4IU/dL。