The B-Natural study—The outcome of immune tolerance induction therapy in patients with severe haemophilia B

Research output: Contribution to journalArticle

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.

Details

Authors
  • Jan Astermark
  • Katharina Holstein
  • Yasmina L. Abajas
  • Susan Kearney
  • Stacy E. Croteau
  • Riana Liesner
  • Eva Funding
  • Christine L. Kempton
  • Suchitra Acharya
  • Stefan Lethagen
  • Petra LeBeau
  • Joel Bowen
  • Erik Berntorp
  • Amy D. Shapiro
Organisations
External organisations
  • Skåne University Hospital
  • University Medical Center Hamburg-Eppendorf
  • University of North Carolina
  • Boston Children's Hospital
  • Great Ormond Street Hospital
  • Copenhagen University Hospital
  • Emory University
  • Northwell Haemostasis and Thrombosis Centre
  • Swedish Orphan Biovitrum
  • Rho, Inc.
  • Children's Minnesota
  • Indiana Haemophilia and Thrombosis Centre
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology

Keywords

  • allergy, factor IX deficiency, haemophilia B, immune tolerance induction, inhibitors, nephrotic syndrome
Original languageEnglish
JournalHaemophilia
Publication statusE-pub ahead of print - 2021
Publication categoryResearch
Peer-reviewedYes