Intermediate-dose immune tolerance induction outperforms with faster success, less bleeding, and no added cost in comparison with low dose: a multicenter randomized clinical trial

Zhengping Li; Zekun Li; Xiaoling Cheng; Heng Zhang; Can Yang; Qian Xu; Zhenping Chen; Yingzi Zhen; Gang Li; Guoqing Liu; Wanru Yao; Min Zhou; Jiao Jin; Jie Huang; Yongjun Fang; Liangzhi Xie; Man-Chiu Poon; Runhui Wu

Research and Practice in Thrombosis and Haemostasis (Jan 2025)

Intermediate-dose immune tolerance induction outperforms with faster success, less bleeding, and no added cost in comparison with low dose: a multicenter randomized clinical trial

Zhengping Li,
Zekun Li,
Xiaoling Cheng,
Heng Zhang,
Can Yang,
Qian Xu,
Zhenping Chen,
Yingzi Zhen,
Gang Li,
Guoqing Liu,
Wanru Yao,
Min Zhou,
Jiao Jin,
Jie Huang,
Yongjun Fang,
Liangzhi Xie,
Man-Chiu Poon,
Runhui Wu

Affiliations

Zhengping Li: Hemophilia Comprehensive Care Center, Hematology Center, Beijing Key Laboratory of Pediatric Hematology-Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China; Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology-Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
Zekun Li: Hemophilia Comprehensive Care Center, Hematology Center, Beijing Key Laboratory of Pediatric Hematology-Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China; Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology-Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
Xiaoling Cheng: Department of Pharmacy, Beijing Children’s Hospital, National Center for Children’s Health, Capital Medical University, Beijing, China
Heng Zhang: Department of Hematology and Oncology, Children's Hospital of Nanjing Medical University, Nanjing, China
Can Yang: Department of Hematology and Oncology, The Affiliated Hospital of Guizhou Medical University, Guizhou, China
Qian Xu: Department of Hematology & Oncology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
Zhenping Chen: Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology-Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
Yingzi Zhen: Hemophilia Comprehensive Care Center, Hematology Center, Beijing Key Laboratory of Pediatric Hematology-Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
Gang Li: Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology-Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
Guoqing Liu: Hemophilia Comprehensive Care Center, Hematology Center, Beijing Key Laboratory of Pediatric Hematology-Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
Wanru Yao: Hemophilia Comprehensive Care Center, Hematology Center, Beijing Key Laboratory of Pediatric Hematology-Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
Min Zhou: Department of Hematology & Oncology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
Jiao Jin: Department of Hematology and Oncology, The Affiliated Hospital of Guizhou Medical University, Guizhou, China
Jie Huang: Department of Hematology and Oncology, Children's Hospital of Nanjing Medical University, Nanjing, China
Yongjun Fang: Department of Hematology and Oncology, Children's Hospital of Nanjing Medical University, Nanjing, China
Liangzhi Xie: Beijing Engineering Research Center of Protein and Antibody, SinoCellTech Ltd, Beijing, China; Liangzhi Xie, Beijing Engineering Research Center of Protein and Antibody, SinoCellTech Ltd, Room 301, Building 5, No. 31 Kechuang 7th Street, Beijing Economic and Technological Development Zone, Beijing, China.
Man-Chiu Poon: Departments of Medicine, Pediatrics and Oncology, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada; Man-Chiu Poon, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada.
Runhui Wu: Hemophilia Comprehensive Care Center, Hematology Center, Beijing Key Laboratory of Pediatric Hematology-Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China; Correspondence Runhui Wu, Hemophilia Comprehensive Care Center, Hematology Center, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, 56 Nanlishi Road, West District, Beijing, China.

Journal volume & issue: Vol. 9, no. 1
p. 102639

Abstract

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Background: Low-dose (LD) or intermediate-dose (MD) immune tolerance induction (ITI) is effective in children with severe hemophilia A (SHA) with high-titer inhibitors (HTIs) and is attractive in countries with economic constraints. However, high-quality evidence of their use is lacking. Objectives: This was a multicenter randomized clinical trial comparing the efficacy, safety, and medication cost between LD-ITI and MD-ITI for SHA-HTI children. Methods: Children with SHA aged 24 months (median, 26.9; range, 24.0-29.5 months). The 2 groups had similar baseline clinical characteristics and similar success rates (93.8% [MD-ITI] vs 86.7% [LD-ITI]). Compared with LD-ITI, MD-ITI patients took a shorter median time to success (4.2 months vs 10.1 months) and partial success (2.7 months vs 6.6 months) and had lower mean rates for all bleeding (0.38/mo vs 1.40/mo) and joint bleeding (0.11/mo vs 0.83/mo). Between the 2 groups, although the MD-ITI group had higher rFVIII consumption (12,775 vs 7680 IU/kg), their total medication costs to success were similar (3626.49 vs 3240.38 US$/kg). Conclusion: For SHA-HTI children, the success rate and cost for MD-ITI and LD-ITI regimens were similar. MD-ITI regimen would be a priority for regions with economic constraints, considering the shorter time to success, better bleeding control, and no increase in medication cost.

Published in Research and Practice in Thrombosis and Haemostasis

ISSN: 2475-0379 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the blood and blood-forming organs
Website: https://www.sciencedirect.com/journal/research-and-practice-in-thrombosis-and-haemostasis

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