Application of a hemophilia mortality framework to the Emicizumab Global Safety Database

Flora Peyvandi, Johnny N. Mahlangu, Steven W. Pipe, Charles R.M. Hay, Glenn F. Pierce, Peter Kuebler, Rebecca Kruse-Jarres, Midori Shima

Research output: Contribution to journalArticlepeer-review

Abstract

Background: As the first non-factor replacement therapy for persons with congenital hemophilia A (PwcHA), emicizumab's safety profile is of particular interest to the community. Objectives: We applied an algorithm for categorization of fatal events contemporaneous to emicizumab using reporter-assessed causality documented in the Roche Emicizumab Global Safety Database. Patients/Methods: All fatalities in PwcHA reported to the database (from clinical trials, pre-market access, and spontaneous post-marketing reports) were categorized into: associated with hemophilia A—hemorrhagic, thrombotic, human immunodeficiency virus (HIV)/hepatitis C virus (HCV), hepatic (non-HCV); associated with general population—trauma/suicide, non-HA-associated conditions; or, unspecified. Reported cause of death was not reassessed. Results: As of cut-off May 15, 2020, 31 fatalities in PwcHA taking emicizumab were reported. Median age at death was 58 years; 51% had factor VIII inhibitors. Fifteen fatalities were considered associated with HA; overall, the most frequent category was hemorrhage (11/31). Of these, six had a history of life-threatening bleeds, and four had a history of intracranial hemorrhage. The remaining HA-associated fatalities were related to HIV/HCV (3/31) and other hepatic causes (1/31). No cases were categorized as thrombotic. Of 10 cases considered not associated with HA, two were categorized as cardiovascular (non-thrombotic), five as infection/sepsis, and one each of trauma/suicide, pulmonary, and malignancy. Six cases were unspecified. Conclusions: No unique risk of death was associated with emicizumab prophylaxis in PwcHA. The data reveal that mortality in PwcHA receiving emicizumab was primarily associated with hemorrhage or non-HA-associated conditions, and was not reported by treaters to be related to emicizumab treatment.

Original languageEnglish
Pages (from-to)32-41
Number of pages10
JournalJournal of Thrombosis and Haemostasis
Volume19
Issue numberS1
DOIs
Publication statusPublished - Jan 2021

Keywords

  • benchmarking
  • cause of death
  • hemophilia A
  • mortality
  • safety

ASJC Scopus subject areas

  • Hematology

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