Risk Factors for Cutaneous Immune‐Related Adverse Events in the Japanese Population: A Retrospective Single‐Center Cohort Study

Immune checkpoint inhibitor (ICI)-driven alterations in the immune system can induce immune-related adverse events (irAEs). Cutaneous irAEs are notable for being the most common and for their early onset; however, the risk factors underlying their development and severity remain unclear. In this study, we retrospectively analyzed 1224 Japanese patients treated with at least one ICI at Yokohama City University Hospital between 2014 and 2024 and identified the risk factors for cutaneous irAEs using multivariable logistic regression analysis. Overall, 145 cutaneous irAEs were identified in 134 patients (10.9%), of which 18 (1.5%) developed grade 4 cutaneous irAEs. Statistical analysis revealed that anti-programmed cell death protein 1 (anti-PD-1) and anti-cytotoxic T-lymphocyte associated protein-4 (anti-CTLA-4) combination therapy was significantly associated with the risk of developing cutaneous irAEs compared with anti-PD-1 (odds ratio [OR] = 3.21; 95% confidence interval [CI], 1.85-5.54; p < 0.001) or anti-PD ligand 1 (OR = 4.53; 95% CI, 2.06-10.34; p < 0.001) monotherapy. A higher baseline eosinophil count (OR = 1.27; 95% CI, 1.06-1.55; p = 0.013) and melanoma (OR = 2.11; 95% CI, 1.17-3.72; p = 0.011) were associated with an increased risk of cutaneous irAEs. Furthermore, female sex (OR = 4.13; 95% CI, 1.36-13.11; p = 0.012) and high baseline monocyte count (OR = 6.68; 95% CI, 1.87-27.61; p = 0.003) were risk factors for grade 4 cutaneous irAEs. These results indicated that anti-PD-1 and anti-CTLA-4 combination therapy, high eosinophil counts, and melanoma were associated with a higher risk of developing cutaneous irAEs, whereas female sex and high monocyte counts were risk factors for severe cutaneous irAEs.