Imlifidase, a new option to optimize the management of patients with hemophilia A on emicizumab - Sorbonne Université Access content directly
Journal Articles Journal of Thrombosis and Haemostasis Year : 2023

Imlifidase, a new option to optimize the management of patients with hemophilia A on emicizumab

Melissa Bou-Jaoudeh
  • Function : Author
Angelina Mimoun
  • Function : Author
Sandrine Delignat
  • Function : Author
Ladislas Capdevila
  • Function : Author
Victoria Daventure
  • Function : Author
Claire Deligne
  • Function : Author
Jordan Dimitrov
  • Function : Author
Valérie Proulle
  • Function : Author

Abstract

Emicizumab is a bispecific chimeric humanized IgG4 that mimics the procoagulant activity of factor VIII (FVIII). Its long half-life and subcutaneous injection route have been life-changing in treating patients with hemophilia A (PwHA) with and without FVIII inhibitors. However, emicizumab only partially mimics FVIII activity; it prevents but does not treat acute bleeds. Emergency management is particularly complicated in patients with FVIII inhibitors on emicizumab prophylaxis, wherein exogenous FVIII is inefficient. We have shown recently that Imlifidase, an IgG-degrading enzyme (IdeS) of bacterial origin, efficiently eliminates human anti-FVIII IgG in a mouse model of severe HA with inhibitors and opens a therapeutic window for the administration of therapeutic FVIII. Here, we investigated the impact of IdeS treatment in HA mice injected with emicizumab. IdeS hydrolyzed emicizumab in vitro and in vivo, albeit at slower rates than another recombinant human monoclonal IgG4. While the F(ab’)2 fragments were rapidly cleared from the circulation, thus leading to a rapid loss of emicizumab procoagulant activity, low amounts of the single-cleaved intermediate IgG persisted for several days. Moreover, the IdeS-mediated elimination of the neutralizing anti-FVIII IgG and restoration of the hemostatic efficacy of exogenous FVIII were not impaired by the presence of emicizumab and polyclonal human IgG in inhibitor-positive HA mice. Our results suggest that IdeS could be administered to inhibitor-positive PwHA under emicizumab prophylaxis to improve and ease the management of breakthrough bleeds or programmed major surgeries.
Fichier principal
Vignette du fichier
230530 article Emi ides clean.pdf (195.73 Ko) Télécharger le fichier
Origin Files produced by the author(s)

Dates and versions

hal-04217783 , version 1 (27-09-2023)

Identifiers

Cite

Melissa Bou-Jaoudeh, Angelina Mimoun, Sandrine Delignat, Ivan Peyron, Ladislas Capdevila, et al.. Imlifidase, a new option to optimize the management of patients with hemophilia A on emicizumab. Journal of Thrombosis and Haemostasis, 2023, 21 (10), pp.2776-2783. ⟨10.1016/j.jtha.2023.06.038⟩. ⟨hal-04217783⟩
8 View
2 Download

Altmetric

Share

Gmail Mastodon Facebook X LinkedIn More