| アブストラクト | INTRODUCTION: The efficacy and safety of elexacaftor/tezacaftor/ivacaftor (ETI) have been established in prospective clinical trials. Liver function test elevations were observed in a greater proportion of patients receiving ETI compared with placebo; however, the relatively small number of patients and short duration of study preclude detection of rare but clinically significant associations with drug-induced liver injury (DILI). To address this gap, we assessed the real-world risk of DILI associated with ETI through data mining of the FDA adverse event reporting system (FAERS). METHODS: Disproportionality analyses were conducted on FAERS data from the fourth quarter of 2019 through the third quarter of 2022. Comparative patient demographics, onset time and outcomes for ETI-DILI were also obtained. RESULTS: 452 reports of DILI associated with ETI were found, representing 2.1 % of all adverse event reports for ETI. All disproportionality measures were significant for ETI-DILI at p < 0.05; the reporting odds ratio (ROR) (2.82) was comparable to that of drugs classified by FDA as "Most-DILI concern". The most notable demographic finding was a male majority (5:4 male to female ratio) for ETI-DILI compared to a female majority (4:5 male to female ratio) for non ETI-DILI. Median ETI-DILI onset time was 50.5 days, and hospitalization was the second most common complication. CONCLUSION: Using FAERS data, ETI was found to be disproportionately associated with DILI. Future research is needed to investigate the hepatotoxic mechanisms and assess potential mitigation strategies for ETI-induced hepatotoxicity. |
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| ジャーナル名 | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society |
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| 投稿日 | 2024/1/18 |
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| 投稿者 | Shi, Alan; Nguyen, Harold; Kuo, C Benson; Beringer, Paul M |
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| 組織名 | Department of Clinical Pharmacy, Mann School of Pharmacy and Pharmaceutical;Sciences, University of Southern California, 1985 Zonal Ave, Los Angeles, CA;90033, USA.;Department of Regulatory and Quality Sciences, Mann School of Pharmacy and;Pharmaceutical Sciences, University of Southern California, 1985 Zonal Ave, Los;Angeles, CA 90033, USA.;90033, USA; USC Anton Yelchin CF Clinic, 1510 San Pablo St, Los Angeles, CA;90033, USA. Electronic address: beringer@usc.edu. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/38233246/ |
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