Risk of Autoimmune Skin Diseases Associated With Immune Checkpoint Inhibitors: A Pharmacovigilance Analysis Using the FAERS Database

Abstract

Background: Immune checkpoint inhibitors (ICIs) revolutionize cancer therapy but frequently cause immune-related adverse events (irAEs), with autoimmune skin diseases (ASDs) being significant toxicities requiring careful management.

Objective: This study explores the association between ICIs and 10 common ASDs using the FAERS database, aiming to identify risk profiles, time-to-onset patterns, and clinical implications.

Methods: A retrospective pharmacovigilance analysis of FAERS data (2011Q1–2024Q4) was conducted, focusing on reports involving seven ICIs. Disproportionality algorithms (ROR, PRR, BCPNN, and MGPS) and statistical methods, including Kaplan–Meier and Weibull models, were employed to evaluate ASD risk and onset patterns.

Results: Among 1670 cases, bullous pemphigoid (BP) showed the strongest association, particularly with PD-1/PD-L1 inhibitors, and other prominent ASDs, including vitiligo, psoriasiform dermatitis, lichen planus, and dermatomyositis. Scleroderma, Henoch–Schönlein purpura, pemphigus, alopecia areata, and systemic lupus erythematosus exhibited limited or inconsistent signals across different ICIs. The median time-to-onset was 143 days, with early onset linked to ipilimumab and atezolizumab. Reports predominantly involved males (62.8%) and patients ≥ 65 years old (51.7%), with the United States and Japan contributing most cases.

Conclusions: BP, vitiligo, psoriasiform dermatitis, lichen planus, and dermatomyositis are key irAEs of ICIs, requiring vigilant monitoring and individualized management strategies. Limitations include biases in spontaneous reporting and underrepresentation of newer ICIs.