Body Mass Index-Related Trends in Adverse Events with Enfortumab Vedotin: Analysis of a Pharmacovigilance Database...

Enfortumab vedotin (EV) is an antibody-drug conjugate used to treat advanced urothelial carcinoma. Although effective, it frequently causes adverse events, particularly skin toxicity. Body mass index (BMI) has been suggested as a risk factor for EV toxicity, but evidence from large-scale studies remains limited. This study investigated the association between BMI and EV toxicity using a national pharmacovigilance database and single-center clinical data. Adverse event reports from the Japanese Adverse Drug Event Report (JADER) database (2004-2025) were stratified by BMI (<22 vs. ≥22 kg/m²). Reporting odds ratios were calculated, and event frequencies were compared using z-tests. Additionally, a retrospective review of medical records was conducted for 17 EV-treated patients at a single institution. Data on dosing and adverse events were collected, and Fisher's exact test was applied. In JADER, a BMI ≥22 kg/m² was associated with increased reporting of skin disorders, pruritus, and toxic epidermal necrolysis (p < 0.05), whereas a BMI <22 kg/m² was associated with more reports of pyelonephritis (p = 0.007). In the clinical cohort, patients with skin toxicity had a higher BMI (25.1 vs. 17.7 kg/m², p = 0.004) and received higher EV doses relative to ideal body weight (IBW) (108.3 vs. 79.9%, p = 0.007) than those without skin toxicity. A high BMI was associated with an increased risk of certain EV-related skin toxicities, potentially exacerbated by dosing based on actual versus IBW, whereas a low BMI may increase susceptibility to infections such as pyelonephritis. Individualizing risk assessment and dosing based on patient physique may improve the safety and efficacy of EV therapy.