Exploring risk factors for endocrine-related immune-related adverse events: Insights from meta-analysis and Mendelian randomization

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.

Keywords

• Endocrine-related immune adverse events
• immune checkpoint inhibitors
• risk factor
• Mendelian analysis
• meta-analysis