Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Astermark, Jan LU ; Holstein, Katharina ; Abajas, Yasmina L. ; Kearney, Susan ; Croteau, Stacy E. ; Liesner, Riana ; Funding, Eva ; Kempton, Christine L. ; Acharya, Suchitra and Lethagen, Stefan LU , et al. (2021) In Haemophilia 27(5). p.802-813
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.... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
allergy, factor IX deficiency, haemophilia B, immune tolerance induction, inhibitors, nephrotic syndrome
in
Haemophilia
volume
27
issue
5
pages
802 - 813
publisher
Wiley-Blackwell
external identifiers
  • scopus:85107740831
  • pmid:34118102
ISSN
1351-8216
DOI
10.1111/hae.14357
language
English
LU publication?
yes
id
c5f9a282-5adc-4dd1-82f0-99179dac8134
date added to LUP
2021-07-20 11:00:25
date last changed
2024-05-18 12:03:37
@article{c5f9a282-5adc-4dd1-82f0-99179dac8134,
  abstract     = {{<p>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.</p>}},
  author       = {{Astermark, Jan and Holstein, Katharina and Abajas, Yasmina L. and Kearney, Susan and Croteau, Stacy E. and Liesner, Riana and Funding, Eva and Kempton, Christine L. and Acharya, Suchitra and Lethagen, Stefan and LeBeau, Petra and Bowen, Joel and Berntorp, Erik and Shapiro, Amy D.}},
  issn         = {{1351-8216}},
  keywords     = {{allergy; factor IX deficiency; haemophilia B; immune tolerance induction; inhibitors; nephrotic syndrome}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{802--813}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Haemophilia}},
  title        = {{The B-Natural study—The outcome of immune tolerance induction therapy in patients with severe haemophilia B}},
  url          = {{http://dx.doi.org/10.1111/hae.14357}},
  doi          = {{10.1111/hae.14357}},
  volume       = {{27}},
  year         = {{2021}},
}