tetano
Editor, Senior Moderator
Clin Transl Sci
. 2022 Jun 9.
doi: 10.1111/cts.13313. Online ahead of print.
Pharmacogenetic variants and risk of remdesivir-associated liver enzyme elevations in Million Veteran Program participants hospitalized with COVID-19
Sony Tuteja[SUP] 1 [/SUP], Zhihong Yu[SUP] 2 [/SUP], Otis Wilson[SUP] 2 [/SUP], Hua-Chang Chen[SUP] 2 [/SUP], Frank Wendt[SUP] 3 [/SUP], Cecilia P Chung[SUP] 2 [/SUP], Shailja C Shah[SUP] 4 [/SUP], Christine M Hunt[SUP] 5 [/SUP], Ayako Suzuki[SUP] 5 [/SUP], Catherine Chanfreau[SUP] 6 [/SUP], Bryan R Gorman[SUP] 7 [/SUP], Jacob Joseph[SUP] 8 [/SUP], Shiuh-Wen Luoh[SUP] 9 [/SUP], Valerio Napolioni[SUP] 10 11 [/SUP], Cassianne Robinson-Cohen[SUP] 12 [/SUP], Ran Tao[SUP] 13 [/SUP], Jin Zhou[SUP] 14 [/SUP], Kyong-Mi Chang[SUP] 1 [/SUP], Adriana M Hung[SUP] 2 [/SUP], VA Million Veteran Program COVID-19 Science Initiative
Affiliations
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.
. 2022 Jun 9.
doi: 10.1111/cts.13313. Online ahead of print.
Pharmacogenetic variants and risk of remdesivir-associated liver enzyme elevations in Million Veteran Program participants hospitalized with COVID-19
Sony Tuteja[SUP] 1 [/SUP], Zhihong Yu[SUP] 2 [/SUP], Otis Wilson[SUP] 2 [/SUP], Hua-Chang Chen[SUP] 2 [/SUP], Frank Wendt[SUP] 3 [/SUP], Cecilia P Chung[SUP] 2 [/SUP], Shailja C Shah[SUP] 4 [/SUP], Christine M Hunt[SUP] 5 [/SUP], Ayako Suzuki[SUP] 5 [/SUP], Catherine Chanfreau[SUP] 6 [/SUP], Bryan R Gorman[SUP] 7 [/SUP], Jacob Joseph[SUP] 8 [/SUP], Shiuh-Wen Luoh[SUP] 9 [/SUP], Valerio Napolioni[SUP] 10 11 [/SUP], Cassianne Robinson-Cohen[SUP] 12 [/SUP], Ran Tao[SUP] 13 [/SUP], Jin Zhou[SUP] 14 [/SUP], Kyong-Mi Chang[SUP] 1 [/SUP], Adriana M Hung[SUP] 2 [/SUP], VA Million Veteran Program COVID-19 Science Initiative
Affiliations
- PMID: 35684976
- DOI: 10.1111/cts.13313
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.