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
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:...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-01-01
|
| Series: | Research and Practice in Thrombosis and Haemostasis |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2475037924003340 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850119955384631296 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Zhengping Li |
| collection | DOAJ |
| description | 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 <8 years with historical/pre-ITI inhibitor titer 5 to 200 Bethesda Units/mL in 3 centers were randomized 1:1 to receive LD-ITI (recombinant factor VIII [rFVIII] 50 IU/kg every other day) or MD-ITI (rFVIII 100 IU/kg/d) from January 2022 to June 2024 (ChiCTR2200056603, https://www.chictr.org.cn). Results: Thirty-one patients (16 in MD-ITI and 15 in LD-ITI) were enrolled and followed for >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. |
| format | Article |
| id | doaj-art-eaed6865edbb4c3eab4cc65bc8ba7346 |
| institution | OA Journals |
| issn | 2475-0379 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj-art-eaed6865edbb4c3eab4cc65bc8ba73462025-08-20T02:35:30ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792025-01-019110263910.1016/j.rpth.2024.102639Intermediate-dose immune tolerance induction outperforms with faster success, less bleeding, and no added cost in comparison with low dose: a multicenter randomized clinical trialZhengping Li0Zekun Li1Xiaoling Cheng2Heng Zhang3Can Yang4Qian Xu5Zhenping Chen6Yingzi Zhen7Gang Li8Guoqing Liu9Wanru Yao10Min Zhou11Jiao Jin12Jie Huang13Yongjun Fang14Liangzhi Xie15Man-Chiu Poon16Runhui Wu17Hemophilia 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, ChinaHemophilia 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, ChinaDepartment of Pharmacy, Beijing Children’s Hospital, National Center for Children’s Health, Capital Medical University, Beijing, ChinaDepartment of Hematology and Oncology, Children's Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Hematology and Oncology, The Affiliated Hospital of Guizhou Medical University, Guizhou, ChinaDepartment of Hematology & Oncology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, ChinaHematologic 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, ChinaHemophilia 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, ChinaHematologic 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, ChinaHemophilia 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, ChinaHemophilia 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, ChinaDepartment of Hematology & Oncology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Hematology and Oncology, The Affiliated Hospital of Guizhou Medical University, Guizhou, ChinaDepartment of Hematology and Oncology, Children's Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Hematology and Oncology, Children's Hospital of Nanjing Medical University, Nanjing, ChinaBeijing 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.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.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.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 <8 years with historical/pre-ITI inhibitor titer 5 to 200 Bethesda Units/mL in 3 centers were randomized 1:1 to receive LD-ITI (recombinant factor VIII [rFVIII] 50 IU/kg every other day) or MD-ITI (rFVIII 100 IU/kg/d) from January 2022 to June 2024 (ChiCTR2200056603, https://www.chictr.org.cn). Results: Thirty-one patients (16 in MD-ITI and 15 in LD-ITI) were enrolled and followed for >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.http://www.sciencedirect.com/science/article/pii/S2475037924003340immune tolerance inductionintermediate doselow doserandomized clinical trialsevere hemophilia A |
| spellingShingle | 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 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 Research and Practice in Thrombosis and Haemostasis immune tolerance induction intermediate dose low dose randomized clinical trial severe hemophilia A |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | immune tolerance induction intermediate dose low dose randomized clinical trial severe hemophilia A |
| url | http://www.sciencedirect.com/science/article/pii/S2475037924003340 |
| work_keys_str_mv | AT zhengpingli intermediatedoseimmunetoleranceinductionoutperformswithfastersuccesslessbleedingandnoaddedcostincomparisonwithlowdoseamulticenterrandomizedclinicaltrial AT zekunli intermediatedoseimmunetoleranceinductionoutperformswithfastersuccesslessbleedingandnoaddedcostincomparisonwithlowdoseamulticenterrandomizedclinicaltrial AT xiaolingcheng intermediatedoseimmunetoleranceinductionoutperformswithfastersuccesslessbleedingandnoaddedcostincomparisonwithlowdoseamulticenterrandomizedclinicaltrial AT hengzhang intermediatedoseimmunetoleranceinductionoutperformswithfastersuccesslessbleedingandnoaddedcostincomparisonwithlowdoseamulticenterrandomizedclinicaltrial AT canyang intermediatedoseimmunetoleranceinductionoutperformswithfastersuccesslessbleedingandnoaddedcostincomparisonwithlowdoseamulticenterrandomizedclinicaltrial AT qianxu intermediatedoseimmunetoleranceinductionoutperformswithfastersuccesslessbleedingandnoaddedcostincomparisonwithlowdoseamulticenterrandomizedclinicaltrial AT zhenpingchen intermediatedoseimmunetoleranceinductionoutperformswithfastersuccesslessbleedingandnoaddedcostincomparisonwithlowdoseamulticenterrandomizedclinicaltrial AT yingzizhen intermediatedoseimmunetoleranceinductionoutperformswithfastersuccesslessbleedingandnoaddedcostincomparisonwithlowdoseamulticenterrandomizedclinicaltrial AT gangli intermediatedoseimmunetoleranceinductionoutperformswithfastersuccesslessbleedingandnoaddedcostincomparisonwithlowdoseamulticenterrandomizedclinicaltrial AT guoqingliu intermediatedoseimmunetoleranceinductionoutperformswithfastersuccesslessbleedingandnoaddedcostincomparisonwithlowdoseamulticenterrandomizedclinicaltrial AT wanruyao intermediatedoseimmunetoleranceinductionoutperformswithfastersuccesslessbleedingandnoaddedcostincomparisonwithlowdoseamulticenterrandomizedclinicaltrial AT minzhou intermediatedoseimmunetoleranceinductionoutperformswithfastersuccesslessbleedingandnoaddedcostincomparisonwithlowdoseamulticenterrandomizedclinicaltrial AT jiaojin intermediatedoseimmunetoleranceinductionoutperformswithfastersuccesslessbleedingandnoaddedcostincomparisonwithlowdoseamulticenterrandomizedclinicaltrial AT jiehuang intermediatedoseimmunetoleranceinductionoutperformswithfastersuccesslessbleedingandnoaddedcostincomparisonwithlowdoseamulticenterrandomizedclinicaltrial AT yongjunfang intermediatedoseimmunetoleranceinductionoutperformswithfastersuccesslessbleedingandnoaddedcostincomparisonwithlowdoseamulticenterrandomizedclinicaltrial AT liangzhixie intermediatedoseimmunetoleranceinductionoutperformswithfastersuccesslessbleedingandnoaddedcostincomparisonwithlowdoseamulticenterrandomizedclinicaltrial AT manchiupoon intermediatedoseimmunetoleranceinductionoutperformswithfastersuccesslessbleedingandnoaddedcostincomparisonwithlowdoseamulticenterrandomizedclinicaltrial AT runhuiwu intermediatedoseimmunetoleranceinductionoutperformswithfastersuccesslessbleedingandnoaddedcostincomparisonwithlowdoseamulticenterrandomizedclinicaltrial |