Supplementary file 1_Cutaneous adverse reactions associated with enfortumab vedotin: a pharmacovigilance study based on the FDA adverse event reporting system.docx

BackgroundEnfortumab vedotin (EV), a Nectin-4–directed antibody–drug conjugate, improves survival in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) after prior platinum-based chemotherapy and immune checkpoint inhibitors. However, EV-associated cutaneous adverse events (AEs) may be underrecognized in real-world practice.
MethodsWe performed a pharmacovigilance study using the U.S. FDA Adverse Event Reporting System (FAERS) database (2020–2025). EV-related cutaneous AE reports were identified and descriptively characterized. Disproportionality analyses were conducted to detect safety signals, and time-to-onset (TTO) was evaluated. Multivariable analyses were used to explore clinical factors associated with cutaneous AEs and death among EV reports.
ResultsA total of 1,389 EV-associated cutaneous AE cases were identified. The most frequently reported events were rash, pruritus, and alopecia, alongside severe reactions including Stevens–Johnson syndrome and toxic epidermal necrolysis. We detected 44 positive cutaneous safety signals, including 10 not described in the EV label. Most cutaneous AEs occurred early after treatment initiation and were reported predominantly in elderly male patients. Concomitant prednisolone use was associated with higher reporting of cutaneous AEs and increased mortality, whereas concomitant amlodipine use was associated with lower reporting of cutaneous AEs.
ConclusionReal-world FAERS data indicate that enfortumab vedotin is associated with a broad and evolving spectrum of cutaneous adverse events, including early-onset and potentially life-threatening reactions. We identified 10 previously unlabeled safety signals, and most events occurred within the first 2 weeks after treatment initiation. The proposed clinical priority framework may help support risk stratification and pharmacovigilance monitoring. Although causality cannot be established using spontaneous reporting data, these findings highlight the importance of early dermatologic surveillance and individualized safety management during EV therapy.