Ocular adverse events associated with antibody-drug conjugates: a comprehensive pharmacovigilance analysis

Abstract

Introduction: Antibody-drug conjugates (ADCs) are increasingly utilized in patients with solid tumors and hematologic malignancies. However, the adverse ocular toxicity induced by ADCs has not been comprehensively evaluated in real-world clinical settings.

Methods: Data from April 2019 to March 2024 based on the FDA Adverse Event Reporting System (FAERS) were extracted and analyzed. Disproportionality analysis was used to evaluate the association between ADCs and ocular adverse events (AEs). The median time to onset (TTO) of various ADCs was compared.

Results: A comprehensive analysis identified 2,686 ocular AEs associated with ADCs. Among these, Tisotumab vedotin had the most positive signals at the preferred terms (PTs) level, followed by trastuzumab emtansine and enfortumab vedotin. In contrast, gemtuzumab ozogamicin demonstrated minimal ocular toxicity signals. Cluster analysis revealed that ADC-related ocular toxicities predominantly manifested as corneal disorders or ocular neuromuscular disorders. The median onset of ocular toxicity varied considerably, with enfortumab vedotin showing the earliest median onset at 12.5 days.

Conclusions: Our study demonstrates the association between ADCs and ocular AEs based on real-world data, providing valuable guidance for clinicians when prescribing ADCs. And we found some important safety signals that have not been mentioned in the label or previous studies.

Keywords: FAERS; antibody-drug conjugates; ocular adverse events; pharmacovigilance; real-world study.

Figure 1

The flow diagram of the study. DEMO, demographic and administrative information; DRUG, drug information; REACTION, coded AEs.

Figure 2

Radar plots of the distribution of ocular AE at the HLGT level. 1. Vision disorders; 2. Eye disorders NEC; 3. Ocular infections, irritations and inflammations; 4. Ocular neuromuscular disorders; 5. Anterior eye structural change, deposit and degeneration; 6. Ocular hemorrhages and vascular disorders NEC; 7. Ocular structural change, deposit and degeneration NEC; 8. Retina, choroid and vitreous hemorrhages and vascular disorders; 9. Ocular sensory symptoms NEC; 10. Ocular injuries; 11. Glaucoma and ocular hypertension; 12. Ocular neoplasms.

Figure 3

The heatmap showing the associations between ADCs and ocular adverse events at the preferred term level.

Figure 4

Forest plots of ICs under HLGT classification of various ADCs.