An analysis of fatalities in persons with congenital hemophilia A (PwcHA) reported in the FDA Adverse Event Reporting System (FAERS) database

Objective Disease- and treatment-associated mortality is of great interest. The US FAERS database catalogs adverse events reported to the FDA by industry, healthcare providers and patients/carers. We report the results of an analysis of the causes of death in PwcHA over the last 2 decades treated with FDA-approved coagulation products reported to FEARS and compare them across conventional therapies and emicizumab.

Material and Methods The FAERS dashboard was searched for all FDA-approved Factor VIII products and bypass agents covering the period from 1 January 2000 to 31 December 2019. In cases of multi therapy, the first therapy reported was used for classification. Duplications, events outside of congenital HA were excluded; results were categorized according to the HA mortality framework (NHF-abstract#). It was assumed that known limitations of FAERS apply to all products. The analysis was performed without correction of known biases in the reporting of adverse events.

Results Contemporaneous to coagulation product use 723 fatalities (409 cHA, 223 acquired HA, 91 unknown) were identified in FAERS. Excluding acquired HA: North America (31.6%), Asia/Pacific (29.4%), Europe (23.4%), other/unspecified (15.6%). In 39.8% the age was unknown; most patients were ≥41 years (23.4% in 41–65, 18.2% in >65); deaths in patients <18 years (9.4%) and ages 19–40 were reported (9.2%). In 25.8% the cause of death was unknown. Reports from infection/sepsis (10.6%), malignancy (6.8%), cardiac dysfunction (4.0%) were found for all products; fatalities were reported for trauma (4.6%), HIV/HCV (2%), thrombosis (11.0%) and ‘other’ (13.4%). The majority of fatalities were due to hemorrhage (21.8%); nearly 50% of them were intracranial. As of December 31, 2019, 10 fatalities in PwcHA on emicizumab have been reported to FAERS, with causes of death consistent with other coagulation products.

Conclusion This analysis demonstrates a generally consistent pattern of reported mortality in PwcHA across treatment regimens and the utility of a unified approach to cross-examining mortality for all hemostatic agents. Underreporting, variability in reporting, limited case information, and small overall numbers in FAERS hamper classification of cases, highlighting the need for detailed, timely reports for evaluation of mortality risk in PwcHA.

Publication History

Article published online:
18 June 2021