Remdesivir-based therapy improved recovery of patients with COVID-19 in the SARSTer multicentre, real-world study

Flisiak et al., Polish Archives of Internal Medicine, doi:10.20452/pamw.15735, SARSTer

Nov 2020

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Retrospective study comparing 122 remdesivir patients and 211 lopinavir/ritonavir patients, showing higher rates of clinical improvement with remdesivir and lower mortality (not statistically significant).

Gérard, Zhou, Wu, Kamo, Choi, Kim show significantly increased risk of acute kidney injury with remdesivir.

Remdesivir efficacy disappears with longer followup. Mixed-effects meta-regression of efficacy as a function of followup duration across all remdesivir studies shows decreasing efficacy with longer followup7. This may reflect antiviral efficacy being offset by serious adverse effects of treatment.

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risk of death, 48.9% lower, RR 0.51, p = 0.18, treatment 5 of 122 (4.1%), control 17 of 211 (8.1%), NNT 25, odds ratio converted to relative risk, all patients, day 28.

SpO₂<95%, 58.0% lower, RR 0.42, p = 0.13, treatment 4 of 82 (4.9%), control 14 of 119 (11.8%), NNT 15, odds ratio converted to relative risk.

no clinical improvement, 56.5% lower, RR 0.44, p = 0.01, treatment 9 of 122 (7.4%), control 36 of 211 (17.1%), NNT 10, odds ratio converted to relative risk.

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1. Gérard et al., Remdesivir and Acute Renal Failure: A Potential Safety Signal From Disproportionality Analysis of the WHO Safety Database, Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.2145.wiley.com, doi.org.

2. Zhou et al., Acute Kidney Injury and Drugs Prescribed for COVID-19 in Diabetes Patients: A Real-World Disproportionality Analysis, Frontiers in Pharmacology, doi:10.3389/fphar.2022.833679.frontiersin.org, doi.org.

3. Wu et al., Acute Kidney Injury Associated With Remdesivir: A Comprehensive Pharmacovigilance Analysis of COVID-19 Reports in FAERS, Frontiers in Pharmacology, doi:10.3389/fphar.2022.692828.frontiersin.org, doi.org.

4. Kamo et al., Association of Antiviral Drugs for the Treatment of COVID-19 With Acute Renal Failure, In Vivo, doi:10.21873/invivo.13637.iiarjournals.org, doi.org.

5. Choi et al., Comparative effectiveness of combination therapy with nirmatrelvir–ritonavir and remdesivir versus monotherapy with remdesivir or nirmatrelvir–ritonavir in patients hospitalised with COVID-19: a target trial emulation study, The Lancet Infectious Diseases, doi:10.1016/S1473-3099(24)00353-0.sciencedirect.com, doi.org.

6. Kim et al., Investigating the Safety Profile of Fast‐Track COVID‐19 Drugs Using the FDA Adverse Event Reporting System Database: A Comparative Observational Study, Pharmacoepidemiology and Drug Safety, doi:10.1002/pds.70043.wiley.com, doi.org.

7. c19early.org, c19early.org/smeta.html.c19early.org/smeta.html.

Flisiak et al., 3 Nov 2020, retrospective, Poland, peer-reviewed, 23 authors, study period 1 March, 2020 - 31 August, 2020, SARSTer trial. Contact: robert.flisiak1@gmail.com.

This Paper Remdesivir All

Remdesivir-based therapy improved recovery of patients with COVID-19 in the SARSTer multicentre, real-world study

Robert Flisiak, Dorota Zarębska-Michaluk, Aleksandra Berkan-Kawińska, Magdalena Tudrujek-Zdunek, Magdalena Rogalska, Anna Piekarska, Dorota Kozielewicz, Krzysztof Kłos, Marta Rorat, Beata Bolewska, Anna Szymanek-Pasternak, Włodzimierz Mazur, Beata Lorenc, Regina Podlasin, Katarzyna Sikorska, Barbara Oczko-Grzesik, Cezary Iwaszkiewicz, Bartosz Szetela, Paweł Pabjan, Małgorzata Pawłowska, Krzysztof Tomasiewicz, Joanna Polańska, Jerzy Jaroszewicz

Polish Archives of Internal Medicine, doi:10.20452/pamw.15735

Remdesivir use in COVID-19 103 supportive care was available, but the rapid worldwide spread of COVID-19 has raised a desperate need to invent an antiviral agent active against SARS-CoV-2. At first, the search for an effective therapy focused on drug repurposing and new ways of using approved agents with confirmed activity against other viruses. Among them, a compound of lopinavir and ritonavir was identified. Lopinavir, acting as an inhibitor of human immunodeficiency virus (HIV) protease, coadministered with ritonavir to increase its bioavailability, was demonstrated to have in vitro activity against both SARS-CoVs and MERS-CoVs. 1-5 The positive impact of lopinavir / ritonavir on the clinical outcome and reduction of the viral load in nasopharyngeal swabs was documented in patients participating in an open-label study performed during the outbreak of SARS in 2003. 2,3 Three case reports and a single retrospective study focused Introduction In December 2019, a new pathogen associated with an outbreak of respiratory tract infections was discovered in Wuhan, China. It was identified as a novel coronavirus termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), closely related to the already known betacoronaviruses responsible for epidemics named with the acronyms SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome). The outbreak of the disease cause by SARS-CoV-2, coronavirus disease 2019 (COVID-19), was announced a global pandemic by the World Health Organization (WHO) in March 2020. The clinical spectrum of SARS-CoV-2 infection ranges from asymptomatic or mild, selflimited respiratory tract disease to severe progressive pneumonia leading to acute respiratory distress syndrome and death due to multiorgan failure. At the beginning of the epidemic, only

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