Use and effectiveness of remdesivir for the treatment of patients with covid-19 using data from the Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS): a multicentre cohort study

Abstract

Objectives The use of remdesivir (RDV) as the first drug approved for coronavirus disease 2019 (COVID-19) remains controversial. Based on the Lean European Open Survey on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infected patients (LEOSS), we aim to contribute timing-focused complementary real-world insights to its evaluation. Methods SARS-CoV-2 infected patients between January 2020 and December 2021 treated with RDV were matched 1:1 to controls considering sociodemographics, comorbidities and clinical status. Multiple imputations were used to account for missing data. Effects on fatal outcome were estimated using uni- and multivariable Cox regression models. Results We included 9,687 patients. For those starting RDV administration in the complicated phase, Cox regression for fatal outcome showed an adjusted hazard ratio (aHR) of 0.59 (95%CI 0.41–0.83). Positive trends could be obtained for further scenarios: an aHR of 0.51 (95%CI 0.16–1.68) when RDV was initiated in uncomplicated and of 0.76 (95% CI 0.55–1.04) in a critical phase of disease. Patients receiving RDV with concomitant steroids exhibited a further reduction in aHR in both, the complicated (aHR 0.50, 95%CI 0.29–0.88) and critical phase (aHR 0.63, 95%CI 0.39–1.02). Conclusion Our study results elucidate that RDV use, in particular when initiated in the complicated phase and accompanied by steroids is associated with improved mortality. However, given the limitations of non-randomized trials in estimating the magnitude of the benefit of an intervention, further randomized trials focusing on the timing of therapy initiation seem warranted.

Remdesivir Use in the Real-World Setting: An Overview of Available Evidence

“…Rapid elimination of SARS-CoV-2 was observed (median 6 vs. 16 days; p < 0.001) [41]. Among COVID-19 patients with complicated disease or those admitted to the ICU, those with concurrent use of corticosteroids displayed a reduced in-hospital mortality rate [42,43], in agreement with previous results from the RECOVERY trial [44]. Treatment with dexamethasone, RDV, or both in patients hospitalized with COVID-19 was associated with a lower frequency of neurological complications in an additive manner, such that the greatest benefit was observed in patients who received both drugs together [45].…”

Corticosteroids in COVID-19: pros and cons

“…A combination of nirmatrelvir-ritonavir (paxlovid) showed improved outcomes such as mortality ( 61 ). Remdesivir was the first antiviral agent approved for COVID-19 and has continued to be recommended as it has remained effective in improving outcomes in patients with mild to moderate COVID-19 ( 62 , 63 ). Other antiviral agents approved for COVID-19 include molnupiravir and nirmatrelvir, and these agents have been showed to be continuously effective despite the emerging strains such as the Omicron variant ( 64 ).…”