Body Mass Index-related Trends in Adverse Events with Enfortumab Vedotin: Analysis of a Pharmacovigilance Database and Medical Records

Background Enfortumab vedotin (EV) is an antibody–drug conjugate used to treat advanced urothelial carcinoma. Although EV therapy is effective, adverse events—particularly skin disorders—pose a challenge to optimal treatment. Previous reports suggest that body mass index (BMI) may influence the risk of such adverse events, but large-scale analyses and clinical validation are limited. This study aimed to investigate the association between BMI and EV-related adverse events using both a national pharmacovigilance database and single-center medical records. Methods Adverse event reports were extracted from the Japanese Adverse Drug Event Report (JADER) database (2004 Q2–2024 Q3), stratified by BMI (< 22 vs ≥ 22 kg/m²). Reporting odds ratios (RORs) and 95% confidence intervals were calculated for each event, and z-tests were used to compare frequencies between BMI groups. Volcano plots visualized disproportionate reporting. A retrospective medical record review was conducted at a single institution, including 17 patients receiving EV therapy. Patient demographics, treatment dosing, and adverse events were collected. Fisher’s exact test was used for categorical comparisons, and descriptive statistics were reported. Results In JADER, patients with BMI ≥ 22 kg/m² had higher reporting frequencies of skin disorders, pruritus, hyperglycemia, and toxic epidermal necrolysis (p < 0.05), whereas low-BMI patients showed increased reports of pyelonephritis (p = 0.007). Retrospective review confirmed that patients who developed skin toxicity had significantly higher BMI and body weight than those without (mean BMI 25.1 vs 17.7 kg/m², p = 0.004; mean weight 63.9 vs 45.8 kg, p = 0.020). These patients also received higher doses relative to ideal body weight (108.3% vs 79.9%, p = 0.007), suggesting a potential contribution of relative overdose to skin toxicity. Conclusions High BMI is associated with an increased risk of EV-related skin disorders, potentially exacerbated by dosing based on actual rather than ideal body weight. Conversely, low BMI may increase susceptibility to infections such as pyelonephritis. These findings support individualized risk assessment and dosing strategies based on patient physique, contributing to safer and more effective EV therapy. Trial Registration Not applicable