PMID- 38384285
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240224
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 15
DP  - 2024
TI  - A pharmacovigilance study on antibody-drug conjugate (ADC)-related neurotoxicity 
      based on the FDA adverse event reporting system (FAERS).
PG  - 1362484
LID - 10.3389/fphar.2024.1362484 [doi]
LID - 1362484
AB  - Background: Antibody-drug conjugates (ADCs) are a relatively new class of 
      anticancer agents that use monoclonal antibodies to specifically recognize tumour 
      cell surface antigens. However, off-target effects may lead to severe adverse 
      events. This study evaluated the neurotoxicity of ADCs using the FDA Adverse 
      Event Reporting System (FAERS) database. Research design and methods: Data were 
      extracted from the FAERS database for 2004 Q1 to 2022 Q4. We analysed the 
      clinical characteristics of ADC-related neurological adverse events (AEs). We 
      used the reporting odds ratio (ROR) and proportional reporting ratio (PRR) for 
      the disproportionality analysis to evaluate the potential association between AEs 
      and ADCs. Results: A total of 562 cases of neurological AEs were attributed to 
      ADCs. The median age was 65 years old [(Min; Max) = 3; 92]. Neurotoxic signals 
      were detected in patients receiving brentuximab vedotin, enfortumab vedotin, 
      polatuzumab vedotin, trastuzumab emtansine, gemtuzumab ozogamicin, inotuzumab 
      ozogamicin, and trastuzumab deruxtecan. The payloads of brentuximab vedotin, 
      enfortumab vedotin, polatuzumab vedotin, and trastuzumab emtansine were 
      microtubule polymerization inhibitors, which are more likely to develop 
      neurotoxicity. We also found that brentuximab vedotin- and gemtuzumab 
      ozogamicin-related neurological AEs were more likely to result in serious 
      outcomes. The eight most common ADC-related nervous system AE signals were 
      peripheral neuropathy [ROR (95% CI) = 16.98 (14.94-19.30), PRR (95% CI) = 16.0 
      (14.21-18.09)], cerebral haemorrhage [ROR (95% CI) = 9.45 (7.01-12.73), PRR (95% 
      CI) = 9.32 (6.95-12.50)], peripheral sensory neuropathy [ROR (95% CI) = 47.87 
      (33.13-69.19), PRR (95% CI) = 47.43 (32.93-68.30)], polyneuropathy [ROR (95% CI) 
      = 26.01 (18.61-36.33), PRR (95% CI) = 25.75 (18.50-35.86)], encephalopathy [ROR 
      (95% CI) = 5.16 (3.32-8.01), PRR (95% CI) = 5.14 (3.32-7.96)], progressive 
      multifocal leukoencephalopathy [ROR (95% CI) = 22.67 (14.05-36.58), PRR (95% CI) 
      = 22.52 (14.01-36.21)], taste disorder [ROR (95% CI) = 26.09 (15.92-42.76), PRR 
      (95% CI) = 25.78 (15.83-42.00)], and guillain barrier syndrome [ROR (95% CI) = 
      17.844 (10.11-31.51), PRR (95% CI) = 17.79 (10.09-31.35)]. The mortality rate 
      appeared to be relatively high concomitantly with AEs in the central nervous 
      system. Conclusion: ADCs may increase the risk of neurotoxicity in cancer 
      patients, leading to serious mortality. With the widespread application of newly 
      launched ADC drugs, combining the FAERS data with other data sources is crucial 
      for monitoring the neurotoxicity of ADCs. Further studies on the potential 
      mechanisms and preventive measures for ADC-related neurotoxicity are necessary.
CI  - Copyright (c) 2024 Tang, Sun, Liu, Wu and Ding.
FAU - Tang, Linlin
AU  - Tang L
AD  - Department of Pharmacy, Affiliated Hospital of Weifang Medical University, 
      Weifang, China.
FAU - Sun, Cuicui
AU  - Sun C
AD  - Department of Pharmacy, Qilu Hospital of Shandong University, Ji'nan, China.
FAU - Liu, Wenshan
AU  - Liu W
AD  - Department of Pharmacy, Affiliated Hospital of Weifang Medical University, 
      Weifang, China.
FAU - Wu, Haiyan
AU  - Wu H
AD  - Department of Pharmacy, Central Hospital Affiliated to Shandong First Medical 
      University, Ji'nan, China.
FAU - Ding, Chuanhua
AU  - Ding C
AD  - Department of Pharmacy, Affiliated Hospital of Weifang Medical University, 
      Weifang, China.
LA  - eng
PT  - Journal Article
DEP - 20240207
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC10879374
OTO - NOTNLM
OT  - FAERS
OT  - antibody-drug conjugates (ADCs)
OT  - data mining
OT  - neurotoxicity
OT  - pharmacovigilance
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2024/02/22 06:42
MHDA- 2024/02/22 06:43
PMCR- 2024/02/07
CRDT- 2024/02/22 03:40
PHST- 2023/12/28 00:00 [received]
PHST- 2024/01/29 00:00 [accepted]
PHST- 2024/02/22 06:43 [medline]
PHST- 2024/02/22 06:42 [pubmed]
PHST- 2024/02/22 03:40 [entrez]
PHST- 2024/02/07 00:00 [pmc-release]
AID - 1362484 [pii]
AID - 10.3389/fphar.2024.1362484 [doi]
PST - epublish
SO  - Front Pharmacol. 2024 Feb 7;15:1362484. doi: 10.3389/fphar.2024.1362484. 
      eCollection 2024.