| アブストラクト | Tocilizumab and baricitinib are used in rheumatoid arthritis (RA) and COVID-19, where acute hyperinflammation and systemic stress may amplify cardiovascular risk. Comparative evidence on indication-specific cardiovascular signals remains scarce; we therefore assessed these signals by indication. We analyzed the FDA Adverse Event Reporting System data from January 2010 to June 2025 to compare cardiovascular adverse events (CVAEs) associated with baricitinib and tocilizumab. Primary outcomes included 6 CVAE categories: cardiac arrhythmias, central nervous system vascular disorders, embolic and thrombotic events, ischemic heart disease, noninfectious myocarditis/pericarditis, and other cardiac disorders. Disproportionality was assessed using the information component (IC) and reporting odds ratio (ROR), stratified by pre- and post-COVID-19 Emergency Use Authorization (EUA) periods and indications (COVID-19 vs RA). Machine learning models were additionally trained to characterize risk patterns for each drug, with feature contributions interpreted using SHapley Additive exPlanations. Among 17,750,053 reports, 5994 CVAEs were identified (baricitinib, n = 965; tocilizumab, n = 5029). Disproportionality was higher in the post-EUA than the pre-EUA period for both baricitinib (IC, 0.84 [IC025, 0.59] to 1.51 [1.39]; ROR, 1.89 [95% confidence interval, 1.62-2.21] to 3.22 [2.98-3.48]) and tocilizumab (0.22 [0.16] to 0.54 [0.47]; 1.18 [1.14-1.23] to 1.50 [1.43-1.57]). Baricitinib for COVID-19 showed the highest disproportionality (IC, 2.90 [IC025, 2.70]; ROR, 11.95 [95% confidence interval, 10.33-13.83]). Gradient boosting machine achieved the highest AUROC (baricitinib, 0.728; tocilizumab, 0.702), and SHapley Additive exPlanations highlighted COVID-19 indication for baricitinib and RA for tocilizumab. Our findings suggest indication-dependent cardiovascular signals when immunomodulators are repurposed for acute viral infections, underscoring the need for context-aware evaluation in drug repurposing. |
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| ジャーナル名 | Medicine |
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| Pubmed追加日 | 2026/10/27 |
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| 投稿者 | Moon, Junmo; Lee, Chaemin; Lee, Seoyeong; Kim, Meehoh; Wen, Xuerong; Branda, Francesco; Oh, Jeongseon; Son, Yejun; Lee, Kyeongmin; Choi, Taelim; Yon, Dong Keon |
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| 組織名 | Center for Digital Health, Medical Science Research Institute, Kyung Hee;University College of Medicine, Seoul, South Korea.;Department of Biology, Kyung Hee University, Seoul, South Korea.;Department of Medicine, Ewha Womans University College of Medicine, Seoul, South;Korea.;Department of Food and Nutrition, Seoul National University College of Human;Ecology, Seoul, South Korea.;Department of Pharmacy Practice and Clinical Research, College of Pharmacy,;University of Rhode Island, Kingston, RI.;Unit of Medical Statistics and Molecular Epidemiology, Universita Campus;Bio-Medico di Roma, Rome, Italy.;Department of Precision Medicine, Kyung Hee University School of Medicine, Seoul,;South Korea.;Department of Pediatrics, Kyung Hee University Medical Center, Kyung Hee |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/42937805/ |
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