Immune tolerance induction in the era of emicizumab - still the first choice for patients with haemophilia A and inhibitors?

Abstract

INTRODUCTION:

The development of inhibitory antibodies is a severe complication of clotting factor replacement therapy in patients with severe haemophilia A (HA). Current World Federation of Hemophilia (WFH) guidelines for haemophilia care indicate that eradication of inhibitors is best achieved through immune tolerance induction (ITI) therapy.

AIM:

The European Collaborative Haemophilia Network conducted a survey to determine whether ITI is still used in the routine management of patients with HA, and whether the availability of emicizumab prophylaxis has influenced treatment decisions.

METHODS:

The survey was conducted in late 2020/early 2021 in 18 centres representing 17 countries in the Europe/Middle East region treating a total of 4955 patients, and included sections specific to patient and centre demographics, treatment protocols (both ITI and prophylactic), inhibitor development and initiation of ITI, treatment success, and the incidence of adverse events.

RESULTS:

While our results indicate that ITI can still be considered a mainstay of treatment for patients with HA with inhibitors, less than daily dosing of ITI in combination with emicizumab prophylaxis is becoming commonplace across the spectrum of disease severity, with initiation being guided by bleeding patterns. The most frequently cited reasons for not initiating emicizumab prophylaxis were availability or reimbursement issues.

CONCLUSION:

ITI remains a mainstay for haemophilia treatment of patients with HA with inhibitors, but emicizumab has become a preferred first-line approach to protect against bleeds and represents an alternative to burdensome ITI in certain patient groups.

• Authors: Katharina Holstein, Sandra Le Quellec, Robert Klamroth, Angelika Batorova, Pål Andre Holme, Victor Jiménez-Yuste, Jan Astermark
• Journal: Haemophilia : the official journal of the World Federation of Hemophilia (Haemophilia) Vol. 28 Issue 2 Pg. 215-222 (Mar 2022) ISSN: 1365-2516 [Electronic] England
• PMID: 34918839 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors. Haemophilia published by John Wiley & Sons Ltd.

Chemical References

• Antibodies, Bispecific
• Antibodies, Monoclonal, Humanized
• emicizumab
• Factor VIII

Topics

• Antibodies, Bispecific (pharmacology, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Factor VIII
• Hemophilia A (complications)
• Humans
• Immune Tolerance