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. 2025 Mar 3;26(1):50.
doi: 10.1186/s40360-025-00877-4.

Gastrointestinal toxicity of antibody-drug conjugates: a pharmacovigilance study using the FAERS database

Yanshuo Shi  1   2 , Kaiqing Yao  3 , Jianqun Zhao  1   2 , Yuanyuan Yue  1   2 , Huizhen Wu  4   5
Affiliations

Gastrointestinal toxicity of antibody-drug conjugates: a pharmacovigilance study using the FAERS database

Yanshuo Shi et al. BMC Pharmacol Toxicol. .

Abstract

Background: Antibody-drug conjugate (ADC) product specifications identify gastrointestinal adverse reactions. Nevertheless, there is a scarcity of comparative studies pertaining to these side effects of similar medications. Special attention is warranted for adverse drug reactions (ADRs) affecting the gastrointestinal system that are inadequately documented in the drug literature.

Aims: Utilizing the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), data mining was conducted to analyze gastrointestinal adverse reactions associated with ADCs. This analysis aimed to provide evidence supporting the safe use of ADCs in medical institutions.

Methods: We utilized the Openvigil 2.1 platform to extract adverse event data reported for each ADC from the FAERS database, covering the period from the drug's launch until the second quarter of 2024. For data analysis, we employed the reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods.

Results: A total of 23,886 adverse event reports were retrieved, with nine ADCs identified as the primary suspected drugs, including 1,517 reports of gastrointestinal adverse events linked to ADCs. The average patient age was 59.69 years, with a higher prevalence of female patients (919 patients, 60.58%) than male patients (319 patients, 24.32%). The gastrointestinal toxicity intensity, ranked from highest to lowest, was as follows: inotuzumab ozogamicin (IO) with ROR = 11.12 and PRR = 10.68, gemtuzumab ozogamicin (GO) with ROR = 7.87 and PRR = 7.54, polatuzumab vedotin (PV) with ROR = 6.47 and PRR = 6.20, brentuximab vedotin (BV) with ROR = 5.79 and PRR = 5.61, sacituzumab govitecan (SG) with ROR = 5.19 and PRR = 4.61, mirvetuximab soravtansine (MS) with ROR = 4.37 and PRR = 3.80, trastuzumab deruxtecan (TD) with ROR = 4.22 and PRR = 3.63, trastuzumab emtansine (TE) with ROR = 3.93 and PRR = 3.85, and enfortumab vedotin (EV) with ROR = 3.26 and PRR = 3.02. Adverse events resulted in 237 deaths, 43 life-threatening cases, and 439 initial or prolonged hospitalizations, with TD being the top ranking for deaths and hospitalizations, followed by TE, which presented the highest mortality rate due to adverse events. The most frequent adverse events were nausea (506 cases), diarrhea (262 cases), vomiting (216 cases), ascites (112 cases), colitis (90 cases), pancreatitis (52 cases), and intestinal obstruction (37 cases).

Conclusions: ADCs may increase the risk of gastrointestinal adverse events and thus require vigilant monitoring in clinical practice.

Keywords: Adverse events (AEs); Antibody–drug conjugate (ADCs); Data mining; FAERS database; Gastrointestinal toxicity.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Submission declaration: We affirm the originality of this study, and it has not been submitted to any preprint server. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of the FAERS database’s pipeline for screening ADC-associated gastrointestinal adverse events
Fig. 2
Fig. 2
ROR heatmap of ADC-related gastrointestinal AEs
Fig. 3
Fig. 3
Signal strength of ADC gastrointestinal AEs at the PT level in the FAERS database
See this image and copyright information in PMC

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