| アブストラクト | BACKGROUND: The combination of immune checkpoint inhibitors (ICIs) with acetaminophen (APAP) and non-steroidal anti-inflammatory drugs (NSAIDs) is commonly employed in cancer treatment. However, potential drug-drug interactions (DDIs) between these agents remain poorly understood. Our study aimed to identify interaction signals associated with the concomitant use of ICIs and APAP/NSAIDs. METHODS: Data were obtained from the US FDA Adverse Event Reporting System (FAERS) covering the period from 1 January 2014, to 30 June 2025. Disproportionality analysis was conducted for data mining by calculating the reporting odds ratio and 95% confidence interval (95% CI). Adjusted RORs were analyzed using logistic regression, accounting for age, sex, and reporting year. Further confirmation was performed using both additive and multiplicative models. RESULTS: We identified 4,613 reports related to the combination of immune checkpoint inhibitors (ICIs) with acetaminophen (APAP) and non-steroidal anti-inflammatory drugs (NSAIDs). Significant interaction signals were observed for gastrointestinal disorders (adjusted ROR: 1.57, 95% CI: 1.41-1.70, additive model: 0.0549), investigations (adjusted ROR: 1.27, 95% CI: 1.13-1.43, additive model: 0.3847, multiplicative model: 1.3135), renal and urinary disorders (adjusted ROR: 4.68, 95% CI: 4.19-5.24, additive model: 3.5771, multiplicative model: 3.6312), and skin and subcutaneous tissue disorders (adjusted ROR: 1.64, 95% CI: 1.47-1.83, additive model: 0.6818, multiplicative model: 1.5996). Subset analysis revealed positive interaction signals for the combination of ICIs with APAP in gastrointestinal disorders and investigations, for all APAP/NSAIDs combinations with ICIs in renal and urinary disorders, and for the combination of NSAIDs with ICIs in skin and subcutaneous tissue disorders. CONCLUSION: Based on data from the FAERS, four systemic disorders were identified to be associated with drug-drug interactions (DDIs) resulting from the combined use of ICIs and APAP/NSAIDs. Further preclinical trials and well-designed, large-scale clinical studies are needed to explore the potential pharmacodynamic crosstalk, alterations in inflammatory pathway and changes in the tumor immune microenvironment induced by the co-administration of ICIs with APAP/NSAIDs. This will help deepen the understanding of DDIs associated with this combination therapy. |
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| ジャーナル名 | Frontiers in pharmacology |
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| Pubmed追加日 | 2026/10/24 |
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| 投稿者 | Ren, Xiayang; Xue, Lihui; Wang, Yanfeng; Xiao, Jian |
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| 組織名 | Department of Pharmacy, National Cancer Center, National Clinical Research Center;for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union;Medical College, Beijing, China.;Department of Pharmacy, Beijing Chaoyang District Sanhuan Cancer Hospital,;Beijing, China.;Department of Comprehensive Oncology, National Cancer Center, National Clinical;Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences;and Peking Union Medical College, Beijing, China.;Department of Pharmacy, Xiangya Hospital, Central South University, Changsha,;China. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/42920608/ |
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