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

Tuteja S, Yu Z, Wilson O, Chen HC, Wendt F, Chung CP, Shah SC, Hunt CM, Suzuki A, Chanfreau C, Gorman BR, Joseph J, Luoh SW, Napolioni V, Robinson-Cohen C, Tao R, Zhou J, Chang KM, Hung AM, VA Million Veteran Program COVID-19 Science Initiative. Pharmacogenetic variants and risk of remdesivir-associated liver enzyme elevations in Million Veteran Program participants hospitalized with COVID-19. Clinical and translational science. 2022 Aug 1; 15(8):1880-1886.

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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.




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