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

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.