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While U.S. guidelines suggest hospitalized patients with severe COVID-19 receive remdesivir, the WHO has a conditional recommendation against its use in this setting. WHO guidelines are based, in part, on preliminary results of the WHO-sponsored SOLIDARITY trial (NEJM JW Infect Dis Feb 2021 and N Engl J Med 2021; 384:497), which did not show a reduction in mortality among hospitalized patients who received remdesivir. Now, final SOLIDARITY results have been published and a more nuanced picture has emerged.
In this open-label trial conducted in 35 countries, 8275 inpatients with COVID-19 were randomly assigned to receive remdesivir or control (no study drug). Overall, mortality was similar in both groups (14.5% [remdesivir] and 15.6% [control]). Among those who already required ventilation, mortality was 42.1% (remdesivir) and 38.6% (control). However, among those who did not require ventilation, mortality was lower in the remdesivir group: 11.9% vs. 13.5% (rate ratio, 0.86; P=0.02). Progression to ventilation also occurred less frequently in the remdesivir group.
WHO Solidarity Trial Consortium.Remdesivir and three other drugs for hospitalised patients with COVID-19: Final results of the WHO Solidarity randomised trial and updated meta-analyses. Lancet 2022 May 2; [e-pub]. (https://doi.org/10.1016/S0140-6736(22)00519-0)
Comment
Remdesivir is most likely to be beneficial when initiated early in the course of COVID-19. The PINETREE study showed that remdesivir prevents progression to hospitalization in high-risk outpatients with mild-to-moderate COVID-19 (NEJM JW Infect Dis Feb 2022 and N Engl J Med 2022; 386:305). Studies in hospitalized patients find the benefit of remdesivir is most evident in those who have severe COVID-19 but have not yet progressed to requiring ventilation (NEJM JW Infect Dis Dec 2020 and N Engl J Med 2020;383:1813). For patients hospitalized with COVID-19 and requiring oxygen, I prescribe a combination of remdesivir and dexamethasone — and if progression occurs, I add a second immunomodulatory agent (baricitinib or tocilizumab).