Cutaneous adverse events with antibody-drug conjugates: a FAERS-based pharmacovigilance study

Introduction: Antibody-drug conjugates (ADCs) have revolutionized oncology by integrating the target specificity of monoclonal antibodies with the potency of cytotoxic payloads. However, despite a subset of clinical trials and case reports documenting cutaneous adverse events (CAEs) associated with these agents, comprehensive systematic characterization of ADC-related CAEs remains elusive. Methods: Data extracted from the FDA Adverse Event Reporting System (FAERS) spanning Q1 2004 to Q2 2025 included patient baseline characteristics. Disproportionality analyses-reporting odds ratio (ROR) and information component (IC)-were employed to identify safety signals, along with supplementary assessments of time-to-onset (TTO), clinical outcomes, and age- and gender-stratified risks. Results: A total of 3,631 CAEs were identified. Concomitantly, a set of 31 positive signals (PT) was detected at the preferred term level, encompassing common manifestations such as rash, alopecia, bullous dermatitis, generalized exfoliative dermatitis, onycholysis, spider naevus, as well as rare but severe events with robust signals including Stevens-Johnson syndrome (SJS)-toxic epidermal necrolysis (TEN) overlap and generalized exfoliative dermatitis. Notably, positive PTs exhibited marked drug specificity: enfortumab vedotin was associated with the highest number of positive signals, whereas belantamab mafodotin displayed minimal signals. The median TTO of CAEs was 15 days, with trastuzumab deruxtecan demonstrating the shortest latency. Regarding clinical outcomes, hospitalization (23.4%) and death (7.7%) were prominent. Stratified analyses further revealed that elderly patients and males were more susceptible to ADC-related CAEs. Conclusion: Our findings highlight significant risks of CAEs linked to ADCs, emphasizing the need for risk-stratified monitoring and personalized management. Furthermore, we identified some safety signals of CAEs that are not currently annotated in drug labeling, which provide critical real-world evidence to supplement and extend the limited clinical trial safety data.