Abstract
Cutaneous immune-related adverse events (cirAEs) are the most prevalent complication to arise from immunotherapy and cause significant morbidity. We aimed to determine the spectrum, timing, clinical features, and outcomes of cirAEs by conducting an observational pharmacovigilance study using VigiBase, the World Health Organization's global database of individual case safety reports from over 130 member countries (ClinicalTrials.gov, number NCT04898751). We compared adverse event reporting in patients who received immune checkpoint inhibitors (91,323 adverse events) with those of the full reporting database (18,919,358 adverse events). There were 10,933 cases of cirAEs within 51 distinct dermatologic types, with 27 specific eruptions with disproportionate signal represented (information component [IC](025) > 0). Of these 27 eruptions, there were eight cirAEs with n > 100 reports, including vitiligo (IC(025) = 4.87), bullous pemphigoid (IC(025) = 4.08), lichenoid dermatitis (IC(025) = 3.69), erythema multiforme (IC(025) = 1.03), toxic epidermal necrolysis (IC(025) = 0.95), Stevens‒Johnson syndrome (IC(025) = 0.41), drug eruption (IC(025) = 0.11), and eczematous dermatitis (IC(025) = 0.11). There were differences in time to onset after immune checkpoint inhibitor initiation, with a median of approximately 1 month (erythema multiforme, Stevens‒Johnson syndrome, and toxic epidermal necrolysis), 2 months (drug eruption and eczematous dermatitis), 4 months (lichenoid dermatitis), and 5‒6 months (bullous pemphigoid and vitiligo). CirAEs are diverse, dependent on cancer type, and have distinct and different onset times that are linked to the cirAE subtype.