| アブストラクト | BACKGROUND: Baricitinib is widely used for immune-mediated diseases, yet real-world safety in underrepresented age groups and the temporal dynamics of adverse drug reactions (ADRs) remain insufficiently characterized. OBJECTIVE: To identify age-stratified ADR signals of baricitinib and to examine potential causal roles of Janus kinase (JAK) 1/2 inhibition in key ADRs. DESIGN: A retrospective pharmacovigilance study integrating disproportionality analysis, Mendelian randomization (MR), and time-to-onset (TTO) assessment. METHODS: Baricitinib-associated ADRs reported to the FDA Adverse Event Reporting System (FAERS; Q3-2018 to Q1-2024) were analyzed using Reporting Odds Ratio and Bayesian Confidence Propagation Neural Network, stratified by age (18-65 vs >/=66 years). TTO was modeled to characterize temporal patterns. Two-sample MR using eQTL-based instruments of JAK1/2 expression evaluated causal links with thrombosis and atrial fibrillation (AF). RESULTS: Among 5354 reports, infections were most frequent (28.3%). Thrombotic events (deep vein thrombosis, pulmonary embolism) were more prominent in the elderly (>/=66 years), whereas hepatic enzyme elevation and malignancies were more frequent in adults aged 18-65 years. MR suggested that higher JAK2 expression was protective against thrombosis (OR = 0.998, p = 0.028), whereas higher JAK1 expression conferred increased risk of AF (OR = 1.255, p = 0.043). TTO analysis showed that thrombotic ADRs tended to occur early after baricitinib initiation, whereas certain malignancies emerged later. CONCLUSION: This study highlights distinct age-dependent vulnerabilities to baricitinib-associated ADRs, with genetic evidence suggesting target-specific mechanisms underlying cardiovascular risk. These findings underscore the importance of age-tailored monitoring strategies and proactive pharmacovigilance in clinical practice. |
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| ジャーナル名 | Therapeutic advances in drug safety |
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| Pubmed追加日 | 2025/12/22 |
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| 投稿者 | Zeng, Huiqiong; Liu, Wei; Li, Aidong; Liu, Hanjiang; Li, Xiaojuan; Lai, Junda; Chen, Miaoqian; Xiong, Gaofeng; Zhang, Ye |
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| 組織名 | Traditional Chinese Medicine Department of Rheumatism, Women & Children Health;Institute Futian Shenzhen, Shenzhen, P.R. China.;First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,;Tianjin, China.;National Clinical Research Center for Chinese Medicine Acupuncture and;Moxibustion, Tianjin, China.;Department of Rehabilitation, The Second People's Hospital of Futian District,;Shenzhen, China.;Department of Safety Supervision Division, Guangdong Pharmaceutical Association,;Guangzhou, China.;Department of Public Health, Shenzhen Hospital of Southern Medical University,;Department of Human Life Sciences, Beijing Sport University, Beijing, China.;Department of Laboratory Medicine, Fu Xin Community Health Service Center,;Shenzhen, P.R. China.;Institute Futian Shenzhen, Shenzhen, Guangdong 518000, P.R. China. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/41426305/ |
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