The association of remdesivir and in-hospital outcomes for COVID-19 patients treated with steroids
et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkab256, Aug 2021
PSM retrospective 3,372 hospitalized patients in the USA treated with steroids, showing no significant difference in mortality with remdesivir, but a lower risk of acute kidney injury.
Gérard, Zhou, Wu, Kamo, Choi, Kim show increased risk of acute kidney injury, Leo, Briciu, Muntean, Petrov show increased risk of liver injury, and Negru, Cheng, Mohammed show increased risk of cardiac disorders 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 followup14. This may reflect
antiviral efficacy being offset by serious adverse effects of treatment.
Standard of Care (SOC) for COVID-19 in the study country,
the USA, is very poor with very low average efficacy for approved treatments15.
Only expensive, high-profit treatments were approved for early treatment. Low-cost treatments were excluded, reducing the probability of early treatment due to access and cost barriers, and eliminating complementary and synergistic benefits seen with many low-cost treatments.
This may explain in part the very high mortality seen in this study.
Results may differ in countries with improved SOC.
|
risk of death, 0.9% lower, RR 0.99, p = 0.96, treatment 214 of 999 (21.4%), control 216 of 999 (21.6%), NNT 499, PSM.
|
|
risk of mechanical ventilation, no change, RR 1.00, p = 1.00, treatment 140 of 999 (14.0%), control 140 of 999 (14.0%), PSM.
|
|
risk of ICU admission, 17.1% higher, RR 1.17, p = 0.05, treatment 260 of 999 (26.0%), control 222 of 999 (22.2%), PSM.
|
| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
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.
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.
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8.
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9.
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10.
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12.
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Kuno et al., 9 Aug 2021, retrospective, propensity score matching, USA, peer-reviewed, 6 authors.
The association of remdesivir and in-hospital outcomes for COVID-19 patients treated with steroids
Background: Remdesivir has been shown to decrease SARS-CoV-2 viral loads and the duration of COVID-19 symptoms. However, current evidence regarding the association between remdesivir and in-hospital mortality for patients with COVID-19 steroid treatments is limited. We aimed to investigate whether remdesivir reduces in-hospital mortality among patients with COVID-19 treated with steroids.
Methods: In this retrospective multicentre study, we reviewed the medical records of 3372 patients discharged between 1 March 2020 and 30 March 2021, with laboratory confirmed COVID-19 in the Mount Sinai Health System and treated with steroids. We evaluated the effect of remdesivir on the outcomes using propensity score analyses. Subgroup analyses were conducted by stratification of patients by endotracheal intubation and COVID-19 antibody status. Acute kidney injury (AKI) was defined as an absolute serum creatinine increase of 0.3 mg/dL or a relative increase of 50%. Results: Of the 3372 eligible patients, 1336 (39.6%) received remdesivir. After 1:1 propensity score matching (N = 999 pairs), in-hospital mortality was similar between those with and without remdesivir (21.4% versus 21.6%, respectively, P = 0.96). Remdesivir was not significantly associated with in-hospital mortality regardless of endotracheal intubation or COVID-19 antibody status. However, there was a signal that remdesivir was associated with a reduced risk of AKI in the propensity matched analysis (17.5% versus 23.4%, respectively, P = 0.001). Conclusions: Remdesivir was not associated with reduced risk of in-hospital mortality in patients with COVID-19 treated with steroids but potentially associated with decreased risk of AKI. These findings should be confirmed in prospective studies focusing on COVID-19 patients treated with steroids.
COVID-19 and remdesivir
Author contributions Data curation, full access to all of the data in the study and responsibility taken for the integrity of the data and the accuracy of the data analysis: T.K., M.T. and N.N.E. Study concept and design, and drafting of the manuscript: T.K. Statistical analysis: T.K. and M.T. Administrative, technical, or material support, and study supervision: N.N.E. Acquisition, analysis, or interpretation of data, and critical revision of the manuscript for important intellectual content: all authors.
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DOI record:
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"abstract": "<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Remdesivir has been shown to decrease SARS-CoV-2 viral loads and the duration of COVID-19 symptoms. However, current evidence regarding the association between remdesivir and in-hospital mortality for patients with COVID-19 steroid treatments is limited. We aimed to investigate whether remdesivir reduces in-hospital mortality among patients with COVID-19 treated with steroids.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In this retrospective multicentre study, we reviewed the medical records of 3372 patients discharged between 1 March 2020 and 30 March 2021, with laboratory confirmed COVID-19 in the Mount Sinai Health System and treated with steroids. We evaluated the effect of remdesivir on the outcomes using propensity score analyses. Subgroup analyses were conducted by stratification of patients by endotracheal intubation and COVID-19 antibody status. Acute kidney injury (AKI) was defined as an absolute serum creatinine increase of 0.3 mg/dL or a relative increase of 50%.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Of the 3372 eligible patients, 1336 (39.6%) received remdesivir. After 1:1 propensity score matching (N = 999 pairs), in-hospital mortality was similar between those with and without remdesivir (21.4% versus 21.6%, respectively, P = 0.96). Remdesivir was not significantly associated with in-hospital mortality regardless of endotracheal intubation or COVID-19 antibody status. However, there was a signal that remdesivir was associated with a reduced risk of AKI in the propensity matched analysis (17.5% versus 23.4%, respectively, P = 0.001).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Remdesivir was not associated with reduced risk of in-hospital mortality in patients with COVID-19 treated with steroids but potentially associated with decreased risk of AKI. These findings should be confirmed in prospective studies focusing on COVID-19 patients treated with steroids.</jats:p></jats:sec>",
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