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

Hyunjeong Cho; Ki Young Yoo; Ju-Young Shin; Eun-Kyoung Lee; BongKyoo Choi

doi:10.1016/j.jtha.2024.02.009

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

J Thromb Haemost. 2024 Feb 22:S1538-7836(24)00109-0. doi: 10.1016/j.jtha.2024.02.009. Online ahead of print.

Authors

Hyunjeong Cho¹, Ki Young Yoo², Ju-Young Shin³, Eun-Kyoung Lee⁴, BongKyoo Choi⁵

Affiliations

¹ Department of Research and Development, GC Biopharma, Yongin, South Korea; Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea.
² Korea Hemophilia Foundation, Seoul, South Korea.
³ Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea; School of Pharmacy, Sungkyunkwan University, Suwon, South Korea; Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, South Korea.
⁴ Department of Research and Development, GC Biopharma, Yongin, South Korea.
⁵ Department of Research and Development, GC Biopharma, Yongin, South Korea; Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea. Electronic address: b.choi@gccorp.com.

PMID: 38395359
DOI: 10.1016/j.jtha.2024.02.009

Abstract

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.

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