| アブストラクト | Combining the FDA Adverse Event Reporting System (FAERS) and the Cancer Genome Atlas (TCGA) databases, we aim to explore the factors that influence anti-programmed cell death protein-1 inhibitors/programmed death-ligand-1 (PD-1/PD-L1) related severe cardiac adverse events (cAEs). We obtained anti-PD-1/PD-L1 adverse event reports from January 2014 to December 2022 from the FAERS database. Disproportionality analysis was performed to find anti-PD-1/PD-L1-related cAEs using the proportional reporting ratio (PRR). We were exploring influencing factors based on multivariate logistic regression analysis. Finally, we utilized a strategy that combines FAERS and TCGA databases to explore the potential immune and genetic influencing factors associated with anti-PD-1/PD-L1-related severe cAEs. Reports of severe cAEs accounted for 7.10% of the overall anti-PD-1/PD-L1 adverse event reports in the FAERS database. Immune-mediated myocarditis (PRR = 77.01[59.77-99.23]) shows the strongest toxic signal. The elderly group (65-74: OR = 1.34[1.23-1.47], >/= 75: OR = 1.64[1.49-1.81]), male (OR = 1.14[1.05-1.24]), anti-PD-L1 agents (OR = 1.17[1.03-1.33]), patients with other adverse events (OR = 2.38[2.17-2.60]), and the concomitant use of proton pump inhibitor (OR = 1.29[1.17-1.43]), nonsteroidal anti-inflammatory drugs (OR = 1.17[1.04-1.31]), or antibiotics (OR = 1.24[1.08-1.43]) may increase the risk of severe cAEs. In addition, PD-L1 mRNA (Rs = 0.71, FDR = 2.30 x 10(- 3)) and low-density lipoprotein receptor-related protein 3 (LRP3) (Rs = 0.82, FDR = 2.17 x 10(- 2)) may be immune and genetic influencing factors for severe cAEs. Severe cAEs may be related to antigen receptor-mediated signalling pathways. In this study, we found that age, gender, anti-PD-1/PD-L1 agents, concomitant other adverse events, concomitant medication, PD-L1 mRNA, and LRP3 may be influencing factors for anti-PD-1/PD-L1-related severe cAEs. However, our findings still require a large-scale prospective cohort validation. |
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| ジャーナル名 | Scientific reports |
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| 投稿日 | 2024/9/28 |
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| 投稿者 | Cheng, Xitong; Lin, Jierong; Wang, Bitao; Huang, Shunming; Liu, Maobai; Yang, Jing |
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| 組織名 | Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, China.;College of Pharmacy, Fujian Medical University, Fuzhou, China.;825580125@qq.com.;College of Pharmacy, Fujian Medical University, Fuzhou, China. 825580125@qq.com.;Department of Pharmacy, Union Hospital Affiliated to Fujian Medical University,;No.29, Xinquan Road, Gulou District, Fuzhou, 350001, China. 825580125@qq.com.;Jiangyang@fjmu.edu.cn.;No.29, Xinquan Road, Gulou District, Fuzhou, 350001, China. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/39333574/ |
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