Remdesivir and systemic corticosteroids for the treatment of COVID-19: A Bayesian re-analysis.


Journal

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
ISSN: 1878-3511
Titre abrégé: Int J Infect Dis
Pays: Canada
ID NLM: 9610933

Informations de publication

Date de publication:
Mar 2021
Historique:
received: 24 11 2020
revised: 25 01 2021
accepted: 26 01 2021
pubmed: 5 2 2021
medline: 10 4 2021
entrez: 4 2 2021
Statut: ppublish

Résumé

The global death toll from coronavirus disease 2019 (COVID-19) has exceeded 2 million, and treatments to decrease mortality are needed urgently. To examine the probabilities of a clinically meaningful reduction in mortality for remdesivir and systemic corticosteroids. This was a probabilistic re-analysis of clinical trial data for corticosteroids and remdesivir in the treatment of hospitalized patients with COVID-19 using a Bayesian random effects meta-analytic approach. Studies were identified from existing meta-analyses performed by the World Health Organization. Posterior probabilities of an absolute decrease in mortality compared with control patients, by subgroups based on oxygen requirements, were calculated for corticosteroids and remdesivir. Probabilities of ≥1%, ≥2% and ≥5% absolute decrease in mortality were quantified. For patients needing mechanical ventilation, the probability of ≥1% absolute decrease in mortality was 4% for remdesivir and 93% for corticosteroids. For patients needing supplemental oxygen without mechanical ventilation, the probability of ≥1% absolute decrease in mortality was 81% for remdesivir and 93% for dexamethasone. Finally, for patients who did not need oxygen support, the probability of ≥1% absolute decrease in mortality was 29% for remdesivir and 4% for dexamethasone. Using a Bayesian analytic approach, remdesivir had low probability of achieving a clinically meaningful reduction in mortality, except for patients needing supplemental oxygen without mechanical ventilation. Corticosteroids were more promising for patients needing oxygen support, especially mechanical ventilation. While awaiting more definitive studies, this probabilistic interpretation of the evidence will help to guide treatment decisions for clinicians, as well as guideline and policy makers.

Sections du résumé

BACKGROUND BACKGROUND
The global death toll from coronavirus disease 2019 (COVID-19) has exceeded 2 million, and treatments to decrease mortality are needed urgently.
OBJECTIVES OBJECTIVE
To examine the probabilities of a clinically meaningful reduction in mortality for remdesivir and systemic corticosteroids.
DESIGN, SETTING AND PARTICIPANTS METHODS
This was a probabilistic re-analysis of clinical trial data for corticosteroids and remdesivir in the treatment of hospitalized patients with COVID-19 using a Bayesian random effects meta-analytic approach. Studies were identified from existing meta-analyses performed by the World Health Organization.
MAIN OUTCOMES AND MEASURES METHODS
Posterior probabilities of an absolute decrease in mortality compared with control patients, by subgroups based on oxygen requirements, were calculated for corticosteroids and remdesivir. Probabilities of ≥1%, ≥2% and ≥5% absolute decrease in mortality were quantified.
RESULTS RESULTS
For patients needing mechanical ventilation, the probability of ≥1% absolute decrease in mortality was 4% for remdesivir and 93% for corticosteroids. For patients needing supplemental oxygen without mechanical ventilation, the probability of ≥1% absolute decrease in mortality was 81% for remdesivir and 93% for dexamethasone. Finally, for patients who did not need oxygen support, the probability of ≥1% absolute decrease in mortality was 29% for remdesivir and 4% for dexamethasone.
CONCLUSIONS AND RELEVANCE CONCLUSIONS
Using a Bayesian analytic approach, remdesivir had low probability of achieving a clinically meaningful reduction in mortality, except for patients needing supplemental oxygen without mechanical ventilation. Corticosteroids were more promising for patients needing oxygen support, especially mechanical ventilation. While awaiting more definitive studies, this probabilistic interpretation of the evidence will help to guide treatment decisions for clinicians, as well as guideline and policy makers.

Identifiants

pubmed: 33540128
pii: S1201-9712(21)00077-1
doi: 10.1016/j.ijid.2021.01.065
pmc: PMC7849442
pii:
doi:

Substances chimiques

Adrenal Cortex Hormones 0
remdesivir 3QKI37EEHE
Adenosine Monophosphate 415SHH325A
Alanine OF5P57N2ZX

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

671-676

Informations de copyright

Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Références

Lancet. 2020 May 16;395(10236):1569-1578
pubmed: 32423584
JAMA. 2020 Oct 6;324(13):1307-1316
pubmed: 32876695
Clin Infect Dis. 2021 May 4;72(9):e373-e381
pubmed: 32785710
N Engl J Med. 2020 Nov 5;383(19):1813-1826
pubmed: 32445440
N Engl J Med. 2021 Feb 25;384(8):693-704
pubmed: 32678530
N Engl J Med. 2021 Feb 11;384(6):497-511
pubmed: 33264556
JAMA. 2020 Sep 15;324(11):1048-1057
pubmed: 32821939
JAMA. 2020 Oct 6;324(13):1317-1329
pubmed: 32876697
JAMA. 2020 Oct 6;324(13):1330-1341
pubmed: 32876694
JAMA. 2020 Nov 10;324(18):1827-1828
pubmed: 33057573
BMJ. 1999 Aug 21;319(7208):508-12
pubmed: 10454409

Auteurs

Todd C Lee (TC)

Division of Infectious Diseases, Department of Medicine, McGill University, Montréal, Canada; Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montréal, Canada; Department of Epidemiology, Occupational Health, and Biostatistics, McGill University, Montréal, Canada. Electronic address: todd.lee@mcgill.ca.

Emily G McDonald (EG)

Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montréal, Canada; Division of General Internal Medicine, Department of Medicine, McGill University, Montréal, Canada.

Guillaume Butler-Laporte (G)

Department of Epidemiology, Occupational Health, and Biostatistics, McGill University, Montréal, Canada.

Luke B Harrison (LB)

Division of Infectious Diseases, Department of Medicine, McGill University, Montréal, Canada.

Matthew P Cheng (MP)

Division of Infectious Diseases, Department of Medicine, McGill University, Montréal, Canada.

James M Brophy (JM)

Department of Epidemiology, Occupational Health, and Biostatistics, McGill University, Montréal, Canada; Division of Cardiology, Department of Medicine, McGill University, Montréal, Canada.

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Classifications MeSH