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Remdesivir and systemic corticosteroids for the treatment of COVID-19: A Bayesian re-analysis
Todd C Lee1, Emily G McDonald2, Guillaume Butler-Laporte3
1Division 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.
Background:
The global death toll from coronavirus disease 2019 (COVID-19) has exceeded 2 million, and treatments to decrease mortality are needed urgently.
Objectives:
To examine the probabilities of a clinically meaningful reduction in mortality for remdesivir and systemic corticosteroids.
Design, Setting And Participants:
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:
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:
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:
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.
Insights
Remdesivir showed a low probability of reducing COVID-19 mortality, except in patients needing oxygen. Corticosteroids, particularly dexamethasone, were more effective for patients requiring oxygen support, especially mechanical ventilation.
Area of Science:
- Infectious Diseases
- Critical Care Medicine
- Pharmacology
Background:
- Coronavirus disease 2019 (COVID-19) has caused over 2 million global deaths.
- Urgent need for effective treatments to reduce COVID-19 mortality.
Purpose of the Study:
- To probabilistically re-analyze clinical trial data for remdesivir and systemic corticosteroids.
- To examine the likelihood of a clinically meaningful reduction in mortality for these treatments in COVID-19 patients.
Main Methods:
- Bayesian random effects meta-analysis of existing World Health Organization meta-analyses.
- Calculation of posterior probabilities for absolute mortality decrease (≥1%, ≥2%, ≥5%) by oxygen requirement subgroups.
Main Results:
- For mechanical ventilation patients, remdesivir had 4% probability vs. 93% for corticosteroids.
- For supplemental oxygen patients (no ventilation), remdesivir had 81% probability vs. 93% for dexamethasone.
- For no oxygen support patients, remdesivir had 29% probability vs. 4% for dexamethasone.
Conclusions:
- Remdesivir has a low probability of reducing COVID-19 mortality, except in patients needing supplemental oxygen.
- Corticosteroids demonstrate higher promise for patients needing oxygen support, especially mechanical ventilation.
- Probabilistic analysis aids clinicians and policymakers in COVID-19 treatment decisions pending further studies.
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