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

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

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

Cuicui Sun: Methodology, Data curation, Formal analysis, Writing-original draft. Xiaoyan Yang: Methodology, Data curation. Linlin Tang: Methodology, Data curation. Jinhua Chen: Conceptualization, Formal analysis, Supervision, Writing-review & editing. All authors approved the final version of the manuscript and agreed to be accountable for all aspects of this work.

Acknowledgments

This study was performed using OpenVigil 2.1 based on the FDA Adverse Event Reporting System (FAERS) database and Livertox® database. The information, results, or interpretation of the current study do not represent any opinion of the FDA.

Ethical approval

The FAERS database contains anonymized patient information and no ethical approval was required.

Supplementary Material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14740338.2023.2277801

Additional information

Funding

This paper was funded by Shandong Province Natural Science Foundation (Grant No.ZR2020QH361) and the Special Fund for clinical pharmacy Research of Shandong Medical Association in 2020 (Grant No.YXH2021ZX004).