PMID- 38395359
OWN - NLM
STAT- Publisher
LR  - 20240316
IS  - 1538-7836 (Electronic)
IS  - 1538-7836 (Linking)
DP  - 2024 Feb 22
TI  - 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.
LID - S1538-7836(24)00109-0 [pii]
LID - 10.1016/j.jtha.2024.02.009 [doi]
AB  - 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.
CI  - Copyright (c) 2024 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Cho, Hyunjeong
AU  - Cho H
AD  - Department of Research and Development, GC Biopharma, Yongin, South Korea; 
      Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South 
      Korea.
FAU - Yoo, Ki Young
AU  - Yoo KY
AD  - Korea Hemophilia Foundation, Seoul, South Korea.
FAU - Shin, Ju-Young
AU  - Shin JY
AD  - 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.
FAU - Lee, Eun-Kyoung
AU  - Lee EK
AD  - Department of Research and Development, GC Biopharma, Yongin, South Korea.
FAU - Choi, BongKyoo
AU  - Choi B
AD  - 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.
LA  - eng
PT  - Journal Article
DEP - 20240222
PL  - England
TA  - J Thromb Haemost
JT  - Journal of thrombosis and haemostasis : JTH
JID - 101170508
SB  - IM
OTO - NOTNLM
OT  - United States
OT  - drug safety
OT  - emicizumab
OT  - factor VIII
OT  - thrombosis
COIS- 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.
EDAT- 2024/02/24 11:42
MHDA- 2024/02/24 11:42
CRDT- 2024/02/23 19:18
PHST- 2023/10/25 00:00 [received]
PHST- 2024/02/08 00:00 [revised]
PHST- 2024/02/13 00:00 [accepted]
PHST- 2024/02/24 11:42 [pubmed]
PHST- 2024/02/24 11:42 [medline]
PHST- 2024/02/23 19:18 [entrez]
AID - S1538-7836(24)00109-0 [pii]
AID - 10.1016/j.jtha.2024.02.009 [doi]
PST - aheadofprint
SO  - J Thromb Haemost. 2024 Feb 22:S1538-7836(24)00109-0. doi: 
      10.1016/j.jtha.2024.02.009.