Safety of recombinant activated factor VII for treatment of breakthrough bleeds in patients with congenital haemophilia A and inhibitors receiving emicizumab prophylaxis: Review of the real-world evidence

Haemophilia. 2024 Mar;30(2):267-275. doi: 10.1111/hae.14933. Epub 2024 Jan 30.

Abstract

Background: Emicizumab is used as a subcutaneous prophylaxis for prevention of bleeding episodes in patients with haemophilia A (HA) with and without inhibitors. While low bleeding rates were observed in clinical trials, patients still experience breakthrough bleeds (BTBs) with emicizumab in the real-world. Current guidelines recommend use of recombinant activated factor VII (rFVIIa) for treatment of BTBs in patients with inhibitors. Due to thrombotic events observed in the HAVEN 1 study, activated prothrombin complex concentrate (aPCC) should be used with caution.

Objectives: The objective of this review is to identify and discuss real-world data on the frequency of BTBs and the safety of concomitant rFVIIa use in patients with inhibitors on emicizumab prophylaxis.

Methods: A search of the following databases was conducted on 15 July 2022: BIOSIS Previews® , Current Contents Search® , Embase® , MEDLINE® . Search terms included 'real world', 'haemophilia A', and 'emicizumab'.

Results and conclusions: Eleven relevant publications were identified (seven original research articles and four congress abstracts). The frequency of BTBs specifically for HA patients with inhibitors was described in three publications with 5%-56% patients on emicizumab reporting ≥1 bleeding episode. Treatment of these BTBs appeared to be managed according to relevant guidelines. Importantly, no thrombotic complications occurred during concomitant rFVIIa use. Due to the nature of real-world studies, direct comparison of the results between studies is limited. However, real-world data show that BTBs in inhibitor patients during emicizumab prophylaxis can be safely treated with rFVIIa.

Keywords: blood coagulation factor inhibitors; emicizumab; haemophilia; post-marketing product surveillance; rFVIIa.

Publication types

  • Review

MeSH terms

  • Antibodies, Bispecific* / therapeutic use
  • Antibodies, Monoclonal, Humanized*
  • Factor VIII / therapeutic use
  • Factor VIIa / therapeutic use
  • Hemophilia A* / drug therapy
  • Hemorrhage / prevention & control
  • Humans
  • Recombinant Proteins
  • Thrombosis* / complications

Substances

  • recombinant FVIIa
  • Factor VIIa
  • emicizumab
  • Factor VIII
  • Antibodies, Bispecific
  • Recombinant Proteins
  • Antibodies, Monoclonal, Humanized