Characterizing immune checkpoint inhibitor-related cutaneous adverse reactions: A comprehensive analysis of FDA adverse event reporting system (FAERS) database

Background: The increasing adoption of immune checkpoint inhibitors (ICIs) in clinical settings highlights their efficacy in treating diverse conditions, while also emphasizing the potential for common cutaneous adverse reactions to arise. The aim of this study is to investigate a multitude of impacting factors and determinants among patients presenting with ICI-associated cutaneous adverse reactions.

Methods: We conducted a comprehensive analysis of ICI-associated cutaneous adverse reactions using data from the FAERS. Our study spans from January 1, 2015, to March 31, 2023, focusing on ICIs, including anti-PD-1, anti-PD-L1, and anti-CTLA-4 agents.

Findings: Among the 334,293 reported irAR, 17,431 were identified as cutaneous adverse reactions (ARs). Predominant cutaneous ARs included rash (21.01 %), pruritus (11.22 %), and pemphigoid (3.90 %). Stevens-Johnson syndrome emerged as the most reported severe cutaneous adverse reaction (SCAR) (2.08 %). Anti-CTLA-4 agents exhibited higher cutaneous toxicity compared to anti-PD-1 and anti-PD-L1 agents. Anti-PD-1 agents demonstrated an elevated mortality rate. The combined use of ICIs with chemotherapy amplified the risk of SCAR and mortality. Targeted therapy was a risk factor for cutaneous ARs but was associated with reduced mortality. The median onset day for cutaneous toxicity was 21 days, while for SCAR, it was 23 days. Weight and age were identified as predictors of SCAR, cutaneous toxicity, and mortality. Skin cancer increased skin toxicity, while lung cancer heightened SCAR formation. The number of administered ICIs positively correlated with SCAR, skin toxicity, and mortality.

Interpretation: This study highlights the significance of early identification and effective management of cutaneous toxicities, along with personalized follow-up care, as essential strategies for minimizing risks and preventing treatment disruptions.