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

Plain Language Summary

Endocrine/immune-related adverse events (EirAEs) are complications that can arise from immunotherapy, particularly in cancer treatment. These events can significantly impact patient outcomes and quality of life. Understanding the risk factors associated with these adverse events is crucial for improving patient management and treatment strategies. The primary aim of this study was to identify risk factors for EirAEs and to ascertain whether EirAEs confer better prognosis of immunotherapy. This research is a systematic review and meta-analysis, supplemented by Mendelian randomization analysis, which utilises genetic variants as instrumental variables to assess causal relationships between risk factors and the occurrence of endocrine-related irAEs. Results showed that several risk factors were associated with an increased incidence of endocrine-related irAEs, including elevated baseline thyroid stimulating hormone (TSH), positive TgAb, positive TPOAb, prior thyroid-related medical history, increased body mass index, combination ICIs therapy with targeted treatment, and dual immune checkpoint inhibitors (ICI) therapy. Additionally, cancer patients developing EirAEs following ICIs treatment exhibited significantly prolonged survival time compared to those without. Authors concluded that their findings highlight the importance of considering patient demographics and genetic predispositions when assessing the risk of EirAEs.