A pharmacovigilance study on drug-induced liver injury associated with antibody-drug conjugates (ADCs) based on the food and drug administration adverse event reporting system

Cuicui Sun; Xiaoyan Yang; Linlin Tang; Jinhua Chen

doi:10.1080/14740338.2023.2277801

A pharmacovigilance study on drug-induced liver injury associated with antibody-drug conjugates (ADCs) based on the food and drug administration adverse event reporting system

Expert Opin Drug Saf. 2023 Oct 29:1-12. doi: 10.1080/14740338.2023.2277801. Online ahead of print.

Authors

Cuicui Sun¹, Xiaoyan Yang², Linlin Tang³, Jinhua Chen⁴

Affiliations

¹ Department of Pharmacy, Qilu hospital of Shandong University, Ji'nan, Shandong, China.
² Department of Pharmacy, Jinan Maternity and Child Care Hospital, Ji'nan, Shandong, China.
³ Department of Pharmacy, Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China.
⁴ Department of Pharmacy, Henan Engineering Research Center for Tumor Precision Medicine and Comprehensive Evaluation, Henan Provincial Key Laboratory of Anticancer Drug Research, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, China.

PMID: 37898875
DOI: 10.1080/14740338.2023.2277801

Abstract

Background: This study aimed to assess the association between drug-induced liver injury (DILI) and antibody-drug conjugates (ADCs) by comprehensively evaluating spontaneous reports submitted to the Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2004Q1 to 2022Q3.

Research design and methods: All DILI cases with ADCs as primary suspected drugs were extracted from the FAERS database from 2004Q1 to 2022Q3 using OpenVigil 2.1. The reporting odds ratio (ROR) and the proportional reporting ratio (PRR) for reporting the association between different drugs and DILI risk were calculated.

Results: A total of 504 DILI cases were attributed to ADCs during the study period. Patients with ADCs-related DILI (n = 504) had a mean age of 56.2 ± 18.4 years, with 167 cases not reporting patients' age. Females and males comprised 42.5% and 44.0% of the cases, respectively, while there was no information on gender in 13.5% of the cases. The DILI signals were detected in trastuzumab emtansine, enfortumab vedotin, brentuximab vedotin, polatuzumab vedotin, gemtuzumab ozogamicin, inotuzumab ozogamicin, and trastuzumab deruxtecan.

Conclusions: The FAERS data mining suggested an association between DILI and some ADCs. Further studies are warranted to unraveling the underlying mechanisms and taking preventive measures for ADCs-related DILI.

Keywords: Antibody-drug conjugates (ADCs); drug-induced liver injury (DILI); food and drug administration adverse event reporting system (FAERS); hepatotoxicity; pharmacovigilance.