| アブストラクト | BACKGROUND: With the increasing use of immune checkpoint inhibitors (ICIs) for tumour immunotherapy, the immune-related adverse events (irAEs) caused by their collateral effect on the immune system pose a key challenge for the clinical application of ICIs. Psychiatric adverse events are a class of adverse events associated with ICIs that are realistically observed in the real world. We aim to provide a comprehensive study and summary of psychiatric adverse events associated with ICIs. METHODS: We obtained ICI adverse reaction reports during January 2012-December 2021 from the FDA Adverse Event Reporting System (FAERS) database. ICI reports underwent screening to minimize the influence of other adverse reactions, concomitant medications, and indications for medication use that may also contribute to psychiatric disorders. Disproportionality analysis was performed to find psychiatric adverse events associated with ICIs by comparing ICIs with the full FAERS database using the reporting odds ratio (ROR). Influencing factors were explored based on univariate logistic regression analysis. Finally, the Cancer Genome Atlas (TCGA) pan-cancer transcriptome data were combined to explore the potential biological mechanisms associated with ICI-related pAEs. FINDINGS: Reports of psychiatric adverse events accounted for 2.71% of the overall ICI adverse event reports in the FAERS database. Five categories of psychiatric adverse events were defined as ICI-related psychiatric adverse events (pAEs). The median age of reports with ICI-related pAEs was 70 (interquartile range [IQR] 24-95), with 21.54% of reports having a fatal outcome. Cases with indications for lung cancer, skin cancer and kidney site cancer accounted for the majority. The odds of ICI-related pAEs increased in older patients (65-74: OR = 1.44 [1.22-1.70], P < 0.0001: >/=75: OR = 1.84 [1.54-2.20], P < 0.0001). The occurrence of ICI-related pAEs may be related to NOTCH signalling and dysregulation of synapse-associated pathways. INTERPRETATION: This study investigated psychiatric adverse events highly associated with ICI treatment, their influencing factors and potential biological mechanisms, which provides a reliable basis for further in-depth study of ICI-related pAEs. However, as an exploratory study, our findings need to be further confirmed in a large-scale prospective study. FUNDING: This work was supported by the Natural Science Foundation of Guangdong Province (2018A030313846 and 2021A1515012593), the Science and Technology Planning Project of Guangdong Province (2019A030317020) and the National Natural Science Foundation of China (81802257, 81871859, 81772457, 82172750 and 82172811). Guangdong Basic and Applied Basic Research Foundation (Guangdong - Guangzhou Joint Fouds) (2022A1515111212). This work was supported by Key Research and Development Projects of Sichuan Science and Technology (2022YFS0221, 2022YFS0074, 2022YFS0156 and 2022YFS0378). Sichuan Provincial People's Hospital Hospital Young Talent Fund (2021QN08). |
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| ジャーナル名 | EClinicalMedicine |
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| Pubmed追加日 | 2023/5/3 |
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| 投稿者 | Zhou, Chaozheng; Peng, Shengkun; Lin, Anqi; Jiang, Aimin; Peng, Yuanxi; Gu, Tianqi; Liu, Zaoqu; Cheng, Quan; Zhang, Jian; Luo, Peng |
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| 組織名 | Department of Oncology, Zhujiang Hospital, Southern Medical University,;Guangzhou, China.;Department of Radiology, Sichuan Academy of Medical Sciences and Sichuan;Provincial People's Hospital, University of Electronic Science and Technology of;China, Chengdu, 610072, Sichuan Province, China.;Department of Urology, Changhai Hospital, Naval Medical University (Second;Military Medical University), Shanghai, China.;Department of Interventional Radiology, The First Affiliated Hospital of;Zhengzhou University, Zhengzhou, Henan, China.;Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha,;Hunan, China.;National Clinical Research Center for Geriatric Disorders, Xiangya Hospital,;Central South University, Changsha, China. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/37131541/ |
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