Pharmacogenetic variants and risk of remdesivir‐associated liver enzyme elevations in Million Veteran Program participants hospitalized with COVID‐19

Abstract Remdesivir is the first US Food and Drug Administration (FDA)‐approved drug for the treatment of coronavirus disease 2019 (COVID‐19). We conducted a retrospective pharmacogenetic study to examine remdesivir‐associated liver enzyme elevation among Million Veteran Program participants hospita...

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Main Authors: Sony Tuteja (Author), Zhihong Yu (Author), Otis Wilson (Author), Hua‐Chang Chen (Author), Frank Wendt (Author), Cecilia P. Chung (Author), Shailja C. Shah (Author), Christine M. Hunt (Author), Ayako Suzuki (Author), Catherine Chanfreau (Author), Bryan R. Gorman (Author), Jacob Joseph (Author), Shiuh‐Wen Luoh (Author), Valerio Napolioni (Author), Cassianne Robinson‐Cohen (Author), Ran Tao (Author), Jin Zhou (Author), Kyong‐Mi Chang (Author), Adriana M. Hung (Author), the VA Million Veteran Program COVID‐19 Science Initiative (Author)
Format: Book
Published: Wiley, 2022-08-01T00:00:00Z.
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100 1 0 |a Sony Tuteja  |e author 
700 1 0 |a Zhihong Yu  |e author 
700 1 0 |a Otis Wilson  |e author 
700 1 0 |a Hua‐Chang Chen  |e author 
700 1 0 |a Frank Wendt  |e author 
700 1 0 |a Cecilia P. Chung  |e author 
700 1 0 |a Shailja C. Shah  |e author 
700 1 0 |a Christine M. Hunt  |e author 
700 1 0 |a Ayako Suzuki  |e author 
700 1 0 |a Catherine Chanfreau  |e author 
700 1 0 |a Bryan R. Gorman  |e author 
700 1 0 |a Jacob Joseph  |e author 
700 1 0 |a Shiuh‐Wen Luoh  |e author 
700 1 0 |a Valerio Napolioni  |e author 
700 1 0 |a Cassianne Robinson‐Cohen  |e author 
700 1 0 |a Ran Tao  |e author 
700 1 0 |a Jin Zhou  |e author 
700 1 0 |a Kyong‐Mi Chang  |e author 
700 1 0 |a Adriana M. Hung  |e author 
700 1 0 |a the VA Million Veteran Program COVID‐19 Science Initiative  |e author 
245 0 0 |a Pharmacogenetic variants and risk of remdesivir‐associated liver enzyme elevations in Million Veteran Program participants hospitalized with COVID‐19 
260 |b Wiley,   |c 2022-08-01T00:00:00Z. 
500 |a 1752-8062 
500 |a 1752-8054 
500 |a 10.1111/cts.13313 
520 |a Abstract Remdesivir is the first US Food and Drug Administration (FDA)‐approved drug for the treatment of coronavirus disease 2019 (COVID‐19). We conducted a retrospective pharmacogenetic study to examine remdesivir‐associated liver enzyme elevation among Million Veteran Program participants hospitalized with COVID‐19 between March 15, 2020, and June 30, 2021. Pharmacogene phenotypes were assigned using Stargazer. Linear regression was performed on peak log‐transformed enzyme values, stratified by population, adjusted for age, sex, baseline liver enzymes, comorbidities, and 10 population‐specific principal components. Patients on remdesivir had higher peak alanine aminotransferase (ALT) values following treatment initiation compared with patients not receiving remdesivir. Remdesivir administration was associated with a 33% and 24% higher peak ALT in non‐Hispanic White (NHW) and non‐Hispanic Black (NHB) participants (p < 0.001), respectively. In a multivariable model, NHW CYP2C19 intermediate/poor metabolizers had a 9% increased peak ALT compared with NHW normal/rapid/ultrarapid metabolizers (p = 0.015); this association was not observed in NHB participants. In summary, remdesivir‐associated ALT elevations appear to be multifactorial, and further studies are needed. 
546 |a EN 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
690 |a Public aspects of medicine 
690 |a RA1-1270 
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786 0 |n Clinical and Translational Science, Vol 15, Iss 8, Pp 1880-1886 (2022) 
787 0 |n https://doi.org/10.1111/cts.13313 
787 0 |n https://doaj.org/toc/1752-8054 
787 0 |n https://doaj.org/toc/1752-8062 
856 4 1 |u https://doaj.org/article/7bae9f9cc503422b9e1b5d18da448c25  |z Connect to this object online.