Exploring risk factors for endocrine-related immune-related adverse events: Insights from meta-analysis and Mendelian randomization
Liuliu Quan, Jinsong Liu, Yuxin Wang, Fan Yang, Zixuan Yang, Jie Ju, You Shuai, Tong Wei, Jian Yue, Xue Wang, Jiaqi Meng, Peng Yuan
Abstract
This study utilized meta-analysis and Mendelian randomization (MR) to identify risk factors for endocrine-related immune-related adverse events (EirAEs) and to ascertain whether EirAEs confer better prognosis of immunotherapy. The meta-analysis identified several risk factors for EirAEs, including elevated baseline TSH (OR = 1.30, 95% CI 1.10–1.53), positive TgAb (OR = 14.23, p < .001), positive TPOAb (OR = 3.75, p < .001), prior thyroid-related medical history (OR = 4.19), increased BMI (OR = 1.11), combination immune checkpoint inhibitors (ICIs) therapy with targeted treatment (OR = 2.71, 95% CI 2.11–3.47), and dual ICI therapy (OR = 3.26, 95% CI 2.22–4.79). MR analysis further supported causalities between extreme BMI, hypothyroidism, and irAEs from a genetic perspective. In addition, cancer patients who experienced EirAEs exhibited significantly prolonged PFS (HR = 0.84, 95% CI 0.73–0.97) and OS (HR = 0.59, 95% CI 0.45–0.76) compared to those without. These findings provide valuable insights for clinical decision-making among healthcare professionals and offer direction for future research in this field.