{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T10:24:34Z","timestamp":1777631074093,"version":"3.51.4"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,5,3]],"date-time":"2022-05-03T00:00:00Z","timestamp":1651536000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100009592","name":"Beijing Municipal Science and Technology Commission","doi-asserted-by":"publisher","award":["Z181100001718182"],"award-info":[{"award-number":["Z181100001718182"]}],"id":[{"id":"10.13039\/501100009592","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Development of haemophilia B inhibitors (HBI) results in the ineffectiveness of FIX replacement therapy. Inhibitor eradication by immune tolerance induction (ITI) is therefore necessary. In HBI, ITI even at high FIX dose is less effective and has a higher risk of severe complications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>To characterize clinical features and outcome of ITI on HBI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This retrospective study was conducted in Haemophilia Paediatric Comprehensive Care Centre of China. We used low\u2010dose ITI (25\u201350 FIX IU\/kg\/three\u2010times\u2010weekly to every\u2010other\u2010day) with domestic prothrombin complex concentrate (PCC), combined with two successive immunosuppressive (IS) regimens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixteen HBI children, representing 5.7% of all and 14.4% of our severe registered HB patients, were enroled. Seven cases reported allergic reactions (ARs) proximal to inhibitor development. The historic peak inhibitor titre was median 54.2 (range 4.7\u2013512) BU, and 15 (93.8%) had high\u2010titre inhibitors. Twelve patients adherent to ITI were analysable. Of the nine ITI patients who received rituximab\/prednisone (IS Regimen\u20101), four achieved tolerization in 1.4\u201343.3 months. Two subsequently relapsed but re\u2010tolerized after a second course of IS Regimen\u20101. During ITI, the median treated bleed was .39\/month (82.7% reduction from before ITI), and the incidence of AR and nephrotic syndrome (NS) complications was each at 22% (2\/9). Three ITI patients received modified \u2018Beutel\u2019 protocol (IS Regimen\u20102) using multiple\u2010IS\u2010drugs, and two had rapid tolerization (.8 and 1.8 months).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Inhibitor eradication could be achieved by low\u2010dose ITI protocol using PCC combined with IS. Larger studies are needed to confirm if ITI with IS Regimen\u20102 is more effective with less complications.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.14577","type":"journal-article","created":{"date-parts":[[2022,5,3]],"date-time":"2022-05-03T14:58:21Z","timestamp":1651589901000},"page":"625-632","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Eradication of FIX inhibitor in haemophilia B children using low\u2010dose immune tolerance induction with rituximab\u2010based immunosuppressive agent(s) in China"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1421-4590","authenticated-orcid":false,"given":"Zekun","family":"Li","sequence":"first","affiliation":[{"name":"Haemophilia Comprehensive Care Center, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children's Health National Key Discipline of Pediatrics (Capital Medical University), Beijing Children's Hospital, Capital Medical University  Beijing China"},{"name":"Haematologic 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoqing","family":"Liu","sequence":"additional","affiliation":[{"name":"Haemophilia Comprehensive Care Center, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children's Health National Key Discipline of Pediatrics (Capital Medical University), Beijing Children's Hospital, Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanru","family":"Yao","sequence":"additional","affiliation":[{"name":"Haemophilia Comprehensive Care Center, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children's Health National Key Discipline of Pediatrics (Capital Medical University), Beijing Children's Hospital, Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5273-145X","authenticated-orcid":false,"given":"Zhenping","family":"Chen","sequence":"additional","affiliation":[{"name":"Haematologic 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Li","sequence":"additional","affiliation":[{"name":"Haematologic 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0048-2658","authenticated-orcid":false,"given":"Xiaoling","family":"Cheng","sequence":"additional","affiliation":[{"name":"Pharmacology Department, National Center for Children's Health Beijing Children's Hospital, Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingzi","family":"Zhen","sequence":"additional","affiliation":[{"name":"Haemophilia Comprehensive Care Center, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children's Health National Key Discipline of Pediatrics (Capital Medical University), Beijing Children's Hospital, Capital Medical University  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9987-9099","authenticated-orcid":false,"given":"Di","family":"Ai","sequence":"additional","affiliation":[{"name":"Haemophilia Comprehensive Care Center, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children's Health National Key Discipline of Pediatrics (Capital Medical University), Beijing Children's Hospital, Capital Medical University  Beijing China"},{"name":"Haematologic 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1641-1472","authenticated-orcid":false,"given":"Kun","family":"Huang","sequence":"additional","affiliation":[{"name":"Haemophilia Comprehensive Care Center, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children's Health National Key Discipline of Pediatrics (Capital Medical University), Beijing Children's Hospital, Capital Medical University  Beijing China"},{"name":"Haematologic 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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1201-7550","authenticated-orcid":false,"given":"Jie","family":"Sun","sequence":"additional","affiliation":[{"name":"Haemophilia Comprehensive Care Center, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; Key Laboratory of Major Diseases in Children, Ministry of Education, National Center for Children's Health National Key Discipline of Pediatrics (Capital Medical University), Beijing Children's Hospital, Capital Medical University  Beijing China"},{"name":"Haematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; Key Laboratory of Major Diseases in Children, Ministry of Education; 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