PMID- 34538863
OWN - NLM
STAT- MEDLINE
DCOM- 20220202
LR  - 20230902
IS  - 1473-5741 (Electronic)
IS  - 0959-4973 (Linking)
VI  - 33
IP  - 1
DP  - 2022 Jan 1
TI  - Caution the arrhythmia association with antibody-drug conjugates: a 
      pharmacovigilance study.
PG  - e228-e234
LID - 10.1097/CAD.0000000000001191 [doi]
AB  - Arrhythmias associated with antibody-drug conjugates (ADCs) are rare but 
      potentially life-threatening adverse events (AEs). No study has systemically 
      compared arrhythmias associations for various marketed ADCs. This needs to be 
      clarified to guide antitumor therapies. We extracted data of patients treated 
      with ADCs registered between 2004 q1 and 2020 q3 from the US Food and Drug 
      Administration adverse event reporting system (FAERS). The medical dictionary for 
      regulatory activities was used to identify arrhythmias cases. Disproportionality 
      analysis was performed by calculating the reporting odds ratios (ROR) with 
      corresponding 95% confidence intervals (95% CI). Clinical characteristics of 
      patients with ADCs-associated arrhythmias and the time to onset of arrhythmias 
      following different ADCs were collected. A total of 140 reports were considered 
      after inclusion criteria were used. Exposure to gemtuzumab ozogamicin (2.23, 
      1.67-2.97; 48 cases) and brentuximab vedotin (1.27, 1.00-1.61; 67 cases) were 
      associated with a positive signal of arrhythmia. The highest number of arrhythmia 
      reports was for brentuximab vedotin (n = 67). Also 88.00% of arrhythmia occurred 
      within 60 days for all these ADCs. Arrhythmia was commonly reported in patients 
      with hematologic tumors and breast cancer. In the time to onset of adverse events 
      after administration, brentuximab vedotin was significantly earlier than 
      gemtuzumab ozogamicin (38.21 vs. 40.50 days; P = 0.0093), and gemtuzumab 
      ozogamicin was significantly earlier than trastuzumab emtansine (40.50 vs. 
      147.50 days; P = 0.0035). We reviewed arrhythmia adverse drug reactions 
      associated with ADCs from the FAERS database. This study is practical for 
      clinicians to enhance the management of arrhythmia associated with ADCs and 
      improve ADCs treatment safety.
CI  - Copyright (c) 2021 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Li, Xiaolin
AU  - Li X
AD  - Department of Pharmacy, Peking Union Medical College Hospital, Peking Union 
      Medical College, Chinese Academy of Medical Sciences.
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Peking Union Medical College, Chinese Academy of 
      Medical Sciences.
FAU - Chen, Gang
AU  - Chen G
AD  - Nephrology Department, Peking Union Medical College Hospital, Peking Union 
      Medical College, Chinese Academy of Medical Sciences, Beijing, China.
FAU - Hu, Yang
AU  - Hu Y
AD  - Department of Pharmacy, Peking Union Medical College Hospital, Peking Union 
      Medical College, Chinese Academy of Medical Sciences.
FAU - Zhao, Bin
AU  - Zhao B
AD  - Department of Pharmacy, Peking Union Medical College Hospital, Peking Union 
      Medical College, Chinese Academy of Medical Sciences.
FAU - Jiang, Jiandong
AU  - Jiang J
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Peking Union Medical College, Chinese Academy of 
      Medical Sciences.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Anticancer Drugs
JT  - Anti-cancer drugs
JID - 9100823
RN  - 0 (Immunoconjugates)
SB  - IM
MH  - Adult
MH  - Age Factors
MH  - Aged
MH  - Arrhythmias, Cardiac/*chemically induced
MH  - Female
MH  - Humans
MH  - Immunoconjugates/*adverse effects
MH  - Male
MH  - Middle Aged
MH  - Odds Ratio
MH  - *Pharmacovigilance
MH  - United States
MH  - United States Food and Drug Administration
EDAT- 2021/09/21 06:00
MHDA- 2022/02/03 06:00
CRDT- 2021/09/20 05:50
PHST- 2021/09/21 06:00 [pubmed]
PHST- 2022/02/03 06:00 [medline]
PHST- 2021/09/20 05:50 [entrez]
AID - 00001813-202201000-00040 [pii]
AID - 10.1097/CAD.0000000000001191 [doi]
PST - ppublish
SO  - Anticancer Drugs. 2022 Jan 1;33(1):e228-e234. doi: 10.1097/CAD.0000000000001191.