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Mortality Rates Among Hospitalized Patients With COVID-19 Infection Treated With Tocilizumab and Corticosteroids: A Bayesian Reanalysis of a Previous Meta-analysis.
JAMA Netw Open. 2022 02 01; 5(2):e220548.JN

Abstract

Importance

A World Health Organization (WHO) meta-analysis found that tocilizumab was associated with reduced mortality in hospitalized patients with COVID-19. However, uncertainty remains concerning the magnitude of tocilizumab's benefits and whether its association with mortality benefit is similar across respiratory subgroups.

Objective

To use bayesian methods to assess the magnitude of mortality benefit associated with tocilizumab and the differences between respiratory support subgroups in hospitalized patients with COVID-19.

Design, Setting, and Participants

A bayesian hierarchical reanalysis of the WHO meta-analysis of tocilizumab studies published in 2020 and 2021 was performed. Main results were estimated using weakly informative priors to exert little influence on the observed data. The robustness of these results was evaluated using vague and informative priors. The studies featured in the meta-analysis were randomized clinical tocilizumab trials of hospitalized patients with COVID-19. Only patients receiving corticosteroids were included.

Interventions

Usual care plus tocilizumab in comparison with usual care or placebo.

Main Outcomes and Measures

All-cause mortality at 28 days after randomization.

Results

Among the 5339 patients included in this analysis, most were men, with mean ages between 56 and 66 years. There were 2117 patients receiving simple oxygen only, 2505 receiving noninvasive ventilation (NIV), and 717 receiving invasive mechanical ventilation (IMV) in 15 studies from multiple countries and continents. Assuming weakly informative priors, the overall odds ratios (ORs) for survival were 0.70 (95% credible interval [CrI], 0.50-0.91) for patients receiving simple oxygen only, 0.81 (95% CrI, 0.63-1.03) for patients receiving NIV, and 0.89 (95% CrI, 0.61-1.22) for patients receiving IMV, respectively. The posterior probabilities of any benefit (OR <1) were notably different between patients receiving simple oxygen only (98.9%), NIV (95.5%), and IMV (75.4%). The posterior probabilities of a clinically meaningful association (absolute mortality risk difference >1%) were greater than 95% in patients receiving simple oxygen only and greater than 90% in patients receiving NIV. In contrast, the posterior probability of this clinically meaningful association was only approximately 67% in patients receiving IMV. The probabilities of tocilizumab superiority in the simple oxygen only subgroup compared with the NIV and IMV subgroups were 85% and 90%, respectively. Predictive intervals highlighted that only 72.1% of future tocilizumab IMV studies would show benefit. The conclusions did not change with different prior distributions.

Conclusions and Relevance

In this bayesian reanalysis of a previous meta-analysis of 15 studies of hospitalized patients with COVID-19 treated with tocilizumab and corticosteroids, use of simple oxygen only and NIV was associated with a probability of a clinically meaningful mortality benefit from tocilizumab. Future research should clarify whether patients receiving IMV also benefit from tocilizumab.

Authors+Show Affiliations

School of Medicine, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.HCor Research Institute, Sao Paulo, Brazil.Department of Internal Medicine, Columbia University, New York, New York.Department of Psychology, University of California, Davis.McGill Health University Center, Montreal, Québec, Canada.

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

35226077

Citation

Albuquerque, Arthur M., et al. "Mortality Rates Among Hospitalized Patients With COVID-19 Infection Treated With Tocilizumab and Corticosteroids: a Bayesian Reanalysis of a Previous Meta-analysis." JAMA Network Open, vol. 5, no. 2, 2022, pp. e220548.
Albuquerque AM, Tramujas L, Sewanan LR, et al. Mortality Rates Among Hospitalized Patients With COVID-19 Infection Treated With Tocilizumab and Corticosteroids: A Bayesian Reanalysis of a Previous Meta-analysis. JAMA Netw Open. 2022;5(2):e220548.
Albuquerque, A. M., Tramujas, L., Sewanan, L. R., Williams, D. R., & Brophy, J. M. (2022). Mortality Rates Among Hospitalized Patients With COVID-19 Infection Treated With Tocilizumab and Corticosteroids: A Bayesian Reanalysis of a Previous Meta-analysis. JAMA Network Open, 5(2), e220548. https://doi.org/10.1001/jamanetworkopen.2022.0548
Albuquerque AM, et al. Mortality Rates Among Hospitalized Patients With COVID-19 Infection Treated With Tocilizumab and Corticosteroids: a Bayesian Reanalysis of a Previous Meta-analysis. JAMA Netw Open. 2022 02 1;5(2):e220548. PubMed PMID: 35226077.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mortality Rates Among Hospitalized Patients With COVID-19 Infection Treated With Tocilizumab and Corticosteroids: A Bayesian Reanalysis of a Previous Meta-analysis. AU - Albuquerque,Arthur M, AU - Tramujas,Lucas, AU - Sewanan,Lorenzo R, AU - Williams,Donald R, AU - Brophy,James M, Y1 - 2022/02/01/ PY - 2022/2/28/entrez PY - 2022/3/1/pubmed PY - 2022/3/8/medline SP - e220548 EP - e220548 JF - JAMA network open JO - JAMA Netw Open VL - 5 IS - 2 N2 - Importance: A World Health Organization (WHO) meta-analysis found that tocilizumab was associated with reduced mortality in hospitalized patients with COVID-19. However, uncertainty remains concerning the magnitude of tocilizumab's benefits and whether its association with mortality benefit is similar across respiratory subgroups. Objective: To use bayesian methods to assess the magnitude of mortality benefit associated with tocilizumab and the differences between respiratory support subgroups in hospitalized patients with COVID-19. Design, Setting, and Participants: A bayesian hierarchical reanalysis of the WHO meta-analysis of tocilizumab studies published in 2020 and 2021 was performed. Main results were estimated using weakly informative priors to exert little influence on the observed data. The robustness of these results was evaluated using vague and informative priors. The studies featured in the meta-analysis were randomized clinical tocilizumab trials of hospitalized patients with COVID-19. Only patients receiving corticosteroids were included. Interventions: Usual care plus tocilizumab in comparison with usual care or placebo. Main Outcomes and Measures: All-cause mortality at 28 days after randomization. Results: Among the 5339 patients included in this analysis, most were men, with mean ages between 56 and 66 years. There were 2117 patients receiving simple oxygen only, 2505 receiving noninvasive ventilation (NIV), and 717 receiving invasive mechanical ventilation (IMV) in 15 studies from multiple countries and continents. Assuming weakly informative priors, the overall odds ratios (ORs) for survival were 0.70 (95% credible interval [CrI], 0.50-0.91) for patients receiving simple oxygen only, 0.81 (95% CrI, 0.63-1.03) for patients receiving NIV, and 0.89 (95% CrI, 0.61-1.22) for patients receiving IMV, respectively. The posterior probabilities of any benefit (OR <1) were notably different between patients receiving simple oxygen only (98.9%), NIV (95.5%), and IMV (75.4%). The posterior probabilities of a clinically meaningful association (absolute mortality risk difference >1%) were greater than 95% in patients receiving simple oxygen only and greater than 90% in patients receiving NIV. In contrast, the posterior probability of this clinically meaningful association was only approximately 67% in patients receiving IMV. The probabilities of tocilizumab superiority in the simple oxygen only subgroup compared with the NIV and IMV subgroups were 85% and 90%, respectively. Predictive intervals highlighted that only 72.1% of future tocilizumab IMV studies would show benefit. The conclusions did not change with different prior distributions. Conclusions and Relevance: In this bayesian reanalysis of a previous meta-analysis of 15 studies of hospitalized patients with COVID-19 treated with tocilizumab and corticosteroids, use of simple oxygen only and NIV was associated with a probability of a clinically meaningful mortality benefit from tocilizumab. Future research should clarify whether patients receiving IMV also benefit from tocilizumab. SN - 2574-3805 UR - https://www.unboundmedicine.com/medline/citation/35226077/Mortality_Rates_Among_Hospitalized_Patients_With_COVID_19_Infection_Treated_With_Tocilizumab_and_Corticosteroids:_A_Bayesian_Reanalysis_of_a_Previous_Meta_analysis_ L2 - https://jamanetwork.com/journals/jamanetworkopen/fullarticle/10.1001/jamanetworkopen.2022.0548 DB - PRIME DP - Unbound Medicine ER -