Jan Astermark1,2, Katharina Holstein3, Yasmina L Abajas4, Susan Kearney5, Stacy E Croteau6, Riana Liesner7, Eva Funding8, Christine L Kempton9, Suchitra Acharya10, Stefan Lethagen11, Petra LeBeau12, Joel Bowen13, Erik Berntorp14, Amy D Shapiro13. 1. Department of Translational Medicine, Lund University, Malmö, Sweden. 2. Department of Haematology, Oncology and Radiation Physics, Skåne University Hospital, Malmö, Sweden. 3. Medical Department, Hemophilia Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 4. Hemophilia and Thrombosis Centre, University of North Carolina, Chapel Hill, North Carolina, USA. 5. Children's Minnesota Centre for Bleeding and Clotting Disorders, Minneapolis, Minnesota, USA. 6. Boston Children's Hospital, Boston Haemophilia Centre, Boston, Massachusetts, USA. 7. Great Ormond Street Hospital for Children, NHS Trust supported by NIHR, GOSH, BRC, London, UK. 8. Department of Haematology, Institute of Clinical Medicine, University Hospital Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 9. Emory University School of Medicine, Emory University, Atlanta, Georgia, USA. 10. Northwell Haemostasis and Thrombosis Centre, New York, New York, USA. 11. Sobi, Stockholm, Sweden. 12. Rho, Inc., Durham, North Carolina, USA. 13. Indiana Haemophilia and Thrombosis Centre, Indianapolis, Indiana, USA. 14. Department of Translational Medicine, Clinical Coagulation Research, Lund University, Malmö, Sweden.
Abstract
INTRODUCTION: Inhibitors develop less frequently in haemophilia B (HB) than haemophilia A (HA). However, when present, the success of tolerization by immune tolerance induction (ITI) therapy is lower and the risk of complications higher. AIM: To evaluate the use and outcome of ITI in patients with HB and inhibitors. METHODS: Subjects include singletons or siblings with a current/history of inhibitors enrolled in B-Natural-an observational study designed to increase understanding of clinical management of patients with HB. Patients were followed for 6 months and information on demographics, medical and social history, and treatment were recorded. RESULTS: Twenty-nine patients with severe HB and inhibitors were enrolled in 24 centres. Twenty-two underwent one or more courses of ITI with or without immune suppression. Eight patients (36.4%) were successfully tolerized after the first course of ITI. One of these successes (12.5%) experienced allergic manifestations, whereas the corresponding number for the 10 treatment failures was five (50%). One of seven (14.2%) patients with large deletions and three of eight (37.5%) with nonsense mutations were tolerized at the first attempt, and all patients experiencing nephrosis either failed or were on-going. At study end, 11 (50%) were considered successfully tolerized after one or more ITI courses, three were unsuccessful, and eight were still undergoing treatment. CONCLUSION: Our data underscore the possibilities and difficulties of achieving tolerization in patients with HB with inhibitors. The type of mutation and complications appear to correlate with ITI outcome, but more accurate definitions of successful ITI are warranted.
INTRODUCTION: Inhibitors develop less frequently in haemophilia B (HB) than haemophilia A (HA). However, when present, the success of tolerization by immune tolerance induction (ITI) therapy is lower and the risk of complications higher. AIM: To evaluate the use and outcome of ITI in patients with HB and inhibitors. METHODS: Subjects include singletons or siblings with a current/history of inhibitors enrolled in B-Natural-an observational study designed to increase understanding of clinical management of patients with HB. Patients were followed for 6 months and information on demographics, medical and social history, and treatment were recorded. RESULTS: Twenty-nine patients with severe HB and inhibitors were enrolled in 24 centres. Twenty-two underwent one or more courses of ITI with or without immune suppression. Eight patients (36.4%) were successfully tolerized after the first course of ITI. One of these successes (12.5%) experienced allergic manifestations, whereas the corresponding number for the 10 treatment failures was five (50%). One of seven (14.2%) patients with large deletions and three of eight (37.5%) with nonsense mutations were tolerized at the first attempt, and all patients experiencing nephrosis either failed or were on-going. At study end, 11 (50%) were considered successfully tolerized after one or more ITI courses, three were unsuccessful, and eight were still undergoing treatment. CONCLUSION: Our data underscore the possibilities and difficulties of achieving tolerization in patients with HB with inhibitors. The type of mutation and complications appear to correlate with ITI outcome, but more accurate definitions of successful ITI are warranted.
Authors: Steven W Pipe; Cédric Hermans; Meera Chitlur; Manuel Carcao; Giancarlo Castaman; Joanna A Davis; Jonathan Ducore; Amy L Dunn; Miguel Escobar; Janna Journeycake; Osman Khan; Johnny Mahlangu; Shannon L Meeks; Ismail Haroon Mitha; Claude Négrier; Ulrike Nowak-Göttl; Michael Recht; Tammuella Chrisentery-Singleton; Oleksandra Stasyshyn; Kateryna V Vilchevska; Laura Villarreal Martinez; Michael Wang; Jerzy Windyga; Guy Young; W Allan Alexander; Daniel Bonzo; Christopher Macie; Ian S Mitchell; Evelyne Sauty; Thomas A Wilkinson; Amy D Shapiro Journal: Haemophilia Date: 2022-04-27 Impact factor: 4.263