Comparison of thrombotic adverse events in patients treated with factor VIII products and emicizumab using the 2018-2022 US Food and Drug Administration Adverse Event Reporting System data.

Publisher: Elsevier Country of Publication: England NLM ID: 101170508 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-7836 (Electronic) Linking ISSN: 15387836 NLM ISO Abbreviation: J Thromb Haemost Subsets: MEDLINE

Publication: 2023- : [New York] : Elsevier
Original Publication: Oxford : Blackwell Pub.

Antibodies, Monoclonal, Humanized*/adverse effects ; Antibodies, Monoclonal, Humanized*/therapeutic use ; Thrombosis*/chemically induced ; Thrombosis*/epidemiology ; Antibodies, Bispecific*/adverse effects ; Factor VIII*/adverse effects ; United States Food and Drug Administration* ; Adverse Drug Reaction Reporting Systems*; Humans ; United States ; Hemophilia A/drug therapy ; Hemophilia A/blood ; Risk Factors ; Coagulants/adverse effects ; Coagulants/therapeutic use ; Risk Assessment ; Databases, Factual

Background: Relatively little is known about thrombotic adverse events (AEs) of emicizumab in postmarketing real-world settings, particularly in comparison with factor VIII (FVIII) products. A recent European study reported a potentially greater thrombotic risk of emicizumab compared with FVIII products.
Objectives: This drug safety study aims to investigate whether thrombotic AEs are more frequently reported for emicizumab than for FVIII products and if so, whether it is independent of bypassing agents as coreporting drugs using the United States Food and Drug Administration Adverse Event Reporting System data.
Methods: Disproportionality analyses for thrombotic AEs of emicizumab vs FVIII products were conducted. Three signal detection indicators were used: proportional reporting ratio (PRR), reporting odds ratio (ROR), and informational component (IC).
Results: During 2018-2022, the proportions of thrombotic AEs among all AEs were 4.07% (97 out of 2383) and 1.44% (134 out of 9324) for emicizumab and FVIII products, respectively: PRR = 2.83 (2.19-3.66), ROR = 2.91 (2.23-3.79), and IC = 1.04 (0.70-1.28). Bypassing agents as coreporting drugs were identified in 36% and 15% of the total thrombotic AE reports associated with emicizumab and FVIII products, respectively. Even after thrombotic AE reports with bypassing agents were excluded, the reporting proportion of thrombotic AEs was still greater for emicizumab than for FVIII products: PRR = 2.19 (1.60-2.99).
Conclusion: Thrombotic AEs in the United States Food and Drug Administration Adverse Event Reporting System data were about 3 times more frequently reported for emicizumab than for FVIII products. More research and efforts in the future are warranted for monitoring, elucidating, and preventing the potential risk of thrombotic AEs in hemophilia therapy, including emicizumab.
Competing Interests: Declaration of competing interests H.C., B.C., and E.L. are employees of GC Biopharma, a biopharmaceutical company, South Korea. There were no AEs of FVIII products of GC Biopharma in the FAERS data. Other authors have competing interests to disclose.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Keywords: United States; drug safety; emicizumab; factor VIII; thrombosis

7NL2E3F6K3 (emicizumab)
0 (Antibodies, Monoclonal, Humanized)
0 (Antibodies, Bispecific)
9001-27-8 (Factor VIII)
839MOZ74GK (F8 protein, human)
0 (Coagulants)

Date Created: 20240223 Date Completed: 20240530 Latest Revision: 20240607

20240607

10.1016/j.jtha.2024.02.009

38395359