Title

IMPACT OF BASELINE ALANINE AMINOTRANSFERASE LEVELS ON THE SAFETY AND EFFICACY OF REMDESIVIR IN MODERATE COVID-19 PATIENTS

Document Type

Conference Proceeding

Publication Date

11-2020

Publication Title

Hepatology

Abstract

Background: Several studies have reported hepatic impairment, in particular abnormal liver function tests in patients with mild to severe COVID-19. Remdesivir (RDV), a nucleotide analogue prodrug that inhibits viral RNA polymerases, has demonstrated favorable clinical efficacy and tolerability in moderate and severe COVID-19 patients. Here, we examined the safety and clinical outcomes in moderate COVID-19 patients with or without elevated baseline (BL) alanine aminotransferase (ALT) levels after RDV treatment.

Methods: We conducted an open-label, phase 3 trial of hospitalized patients with confirmed SARS-CoV-2 infection, oxygen saturation of >94% on room air, and radiological evidence of pneumonia. We randomized participants 1:1:1 to receive 5d or 10d of intravenous RDV once daily plus standard of care (SoC), or SoC only. Patients with ALT or AST> 5x the upper limit of normal (ULN) were excluded. Within this posthoc analysis, we grouped patient using AASLD criteria (ALT 35 U/L for males, 25 U/L for females) into low ALT group (BL ALT ≤ULN) and high ALT group (BL ALT>ULN). Within these ALT groups, we compared those who received RDV vs SoC. Covariates for adjustment included BL demographics (age, sex, race, region and obesity) and disease characteristics (symptom duration, oxygen support status). 2-point clinical improvement and recovery were evaluated using Cox proportional hazards. Clinical outcomes and adverse events (AEs) were assessed through day 28.

Results: Of 584 patients treated with RDV or SoC, 279 (48%) were in the high BL ALT group (183 [66%] RDV, 96 [34%] SoC). BL characteristics were similar for RDV vs SoC arms within high and low ALT groups, except for duration of symptoms before dosing (median RDV 7d vs SoC 9d, p=0.004) in low ALT group. AE profiles were generally similar for RDV vs SoC within high and low ALT groups (Table1). Hepatobiliary adverse events, particularly transaminase elevations, were not common but numerically higher with RDV in both high and low ALT groups. Clinical outcomes, including time to clinical recovery and 2-point clinical improvement were similar for RDV vs SoC within each of the high and low ALT groups.

Conclusion: In moderate COVID-19 patients, the adverse event profile and clinical outcomes of RDV vs SoC was generally similar for those with BL normal ALT and those with elevated ALT (1-5x ULN).

Volume

2020

Issue

72

First Page

88

Last Page

89

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