TY - JOUR
T1 - Pharmacogenetic variants and risk of remdesivir-associated liver enzyme elevations in Million Veteran Program participants hospitalized with COVID-19
AU - the VA Million Veteran Program COVID-19 Science Initiative
AU - Tuteja, Sony
AU - Yu, Zhihong
AU - Wilson, Otis
AU - Chen, Hua Chang
AU - Wendt, Frank
AU - Chung, Cecilia P.
AU - Shah, Shailja C.
AU - Hunt, Christine M.
AU - Suzuki, Ayako
AU - Chanfreau, Catherine
AU - Gorman, Bryan R.
AU - Joseph, Jacob
AU - Luoh, Shiuh Wen
AU - Napolioni, Valerio
AU - Robinson-Cohen, Cassianne
AU - Tao, Ran
AU - Zhou, Jin
AU - Chang, Kyong Mi
AU - Hung, Adriana M.
N1 - Publisher Copyright:
© 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
PY - 2022/8
Y1 - 2022/8
N2 - 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.
AB - 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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U2 - 10.1111/cts.13313
DO - 10.1111/cts.13313
M3 - Article
C2 - 35684976
AN - SCOPUS:85133557381
SN - 1752-8054
VL - 15
SP - 1880
EP - 1886
JO - Clinical and Translational Science
JF - Clinical and Translational Science
IS - 8
ER -