Yuan Xu1,2*, Ying Wang3*, Runhui Wu, MD4*, Changcheng Zheng, MD5*, Jianwen Xiao6*, Weiqun Xu7*, Xiaoqin Feng8*, Hua Wang9*, Xiangshan Cao10*, Liya He11*, Tianyang Xue12*, Mingwei Jin12*, Bingshou Xie13*, Jing Ling, PhD14*, Lirong Sun15*, Rui Su16*, Hongbo Cheng17*, Yongjun Fang18*, Bai Li19*, Ziqiang Yu20*, Ailing Xue21*, Mei Sun22*, Li Yang23*, Zeping Zhou24*, Hu Zhou, MD25*, Jiao Jin26*, Min Zhou27*, Rong Chen28*, Wei Liu, MD1,29*, Lei Zhang, MD2,30, Feng Xue, MD1,2* and Renchi Yang, MD1,31
1Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
2Tianjin Institutes of Health Science, Tianjin, China
3Shenzhen Children's Hospital, Shenzhen, China
4Hematology Department, Beijing Children's Hospital, Affiliated to Capital Medical University, Beijing, China
5Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
6Department of Hematology, Children's Hospital of Chongqing Medical University, Chongqing, China
7Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China
8Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, China
9Xi'an Children's Hospital, Xi'an, China
10Suzhou BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Suzhou, China
11Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
12Xuzhou Star Hospital, Xuzhou, China
13Department of Hematology, The Third Clinical Institute Affiliated to Wenzhou Medical University, People's Hospital of Wenzhou, Wenzhou, China
14Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, China
15Department of Pediatric Hematology and Oncology, Affiliated Hospital of Qingdao University, Qingdao, China
16Department of Hematology, The First Affiliated Hospital of Xiamen University, Xiamen, China
17Department of Hematology, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, Nanchang, China
18Department of Hematology/Oncology, Children's Hospital of Nanjing Medical University, Nanjing, China
19Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
20National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China
21Zibo Central Hospital, Zibo, China
22Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, China
23Department of Hematology, Affiliated Hospital of Nantong University, Nantong, China
24Department of Hematology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
25Henan Cancer Hospital/The Affiliated Cancer Hospital of Zheng Zhou University, Zhengzhou, China
26Department of Pediatrics, Affiliated Hospital of Guizhou Medical University, Guiyang, China
27Chengdu Women's and Children's Central Hospital, Chengdu, China
28Hematology Department, Chengdu Third People's Hospital, Chengdu, China
29State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
30State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Tianjin Key Laboratory of Gene Therapy for Blood Diseases, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Tianjin, China
31State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences&Peking Union Medical College, Tianjin, China
Background
The real-world experiences of Hemophilia A (HA) patients receiving emicizumab prophylaxis in China are insufficient due to the high cost and later approval of emicizumab. In this study, we retrospectively analyzed Chinese HA patients with or without factor VIII (FVIII) inhibitors receiving emicizumab prophylaxis with the aim to investigate the efficacy and safety of emicizumab as well as the current status and effect of different doses of emicizumab in a real-world setting.
Methods
HA patients with or without FVIII inhibitors receiving emicizumab prophylaxis between June 2019 and June 2023 in China were included in the study. Data of HA patients including children and adults were retrospectively gathered from 27 hospitals all over the country. For each patient, the anonymized data were collected and telephone follow-ups were conducted to make sure the intact information collected as much as possible. Low dose and higher dose of emicizumab were defined as monthly dose <3 mg/kg and monthly dose ≥3 mg/kg, respectively. All analyses were performed using SPSS software version 25.0 (IBM Corporation, Armonk, New York, USA). Intraindividual comparisons were performed by nonparametric paired tests.
Results
A total of 127 male patients (10.2% [n=13] ≥18 years old; 89.8% [n=114] <18 years old) were enrolled in our study (severe: moderate = 103:24). Of these, 42 (33.1%) had FVIII inhibitors at initiating emicizumab. The median (interquartile range [IQR]) duration of emicizumab treatment was 16.0 (9.0-30.0) months.
The median (IQR) annualized bleeding rate (ABR) and annualized joint bleeding rate (AJBR) after emicizumab were 0.5 (0-1.5) and 0 (0-0), respectively (calculated in patients treated with emicizumab >6 months). Among the 127 patients, 67 (52.8%) patients had no bleeds at all. No intracranial hemorrhage occurred after emicizumab. Adverse events were reported in 12 (9.4%) patients and 10 (83.3%) were injection-site reactions. There were no deaths, thromboembolic events, or thrombotic microangiopathies in our study.
Two (8.0%) patients had treated epistaxis after emicizumab with low dose compared with 0 (0.0%) with higher dose (P =0.037). Four (16.0%) patients had target joints after emicizumab with low dose compared with 1 (1.0%) with higher dose (P =0.005) (Table 1). There were no significant differences between low dose and higher dose of emicizumab prophylaxis in ABR, AJBR, the proportion of zero bleeds, the proportion of adverse events, and so on.
The median (IQR) ABR was 5.0 (2.0-14.0) with prior treatment compared with 0.5 (0-1.5) with emicizumab, an 90% reduction in ABR with P value <0.001 (Table 2). Also, the use of emicizumab was also associated with significant reduction in AJBR (P <0.001), number of target joints (P <0.001), number of intracerebral hemorrhages (P <0.001), inhibitor titer (P =0.016), and days away from school/work (P <0.001).
Conclusion
In this multi-center study, we indicated the efficacy and safety of emicizumab and that low dose and higher dose of emicizumab had similar efficacy in Chinese HA patients without increasing adverse events.
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