Effect of tocilizumab, sarilumab, and baricitinib on mortality among patients hospitalized for COVID-19 treated with corticosteroids: a systematic review and meta-analysis.

School of Medicine, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Department of Nutrition, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil. HCor Research Institute, São Paulo, Brazil. Division of Infectious Diseases, Department of Medicine, McGill University, Montréal, Canada; Department of Epidemiology, Occupational Health, and Biostatistics, McGill University, Montréal, Canada. Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montréal, Canada; Division of General Internal Medicine, Department of Medicine, McGill University, Montréal, Canada. Department of Epidemiology, Occupational Health, and Biostatistics, McGill University, Montréal, Canada; Division of Cardiology, Department of Medicine, McGill University, Montréal, Canada. Division of Infectious Diseases, Department of Medicine, McGill University, Montréal, Canada; Department of Epidemiology, Occupational Health, and Biostatistics, McGill University, Montréal, Canada; Clinical Practice Assessment Unit, Department of Medicine, McGill University, Montréal, Canada. Electronic address: todd.lee@mcgill.ca.

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2023;(1):13-21

Abstract

BACKGROUND Randomized controlled trials (RCT) established the mortality reduction by tocilizumab (Actemra), baricitinib (Olumiant), and sarilumab (Kevzara) in hospitalized COVID-19 patients. However, uncertainty remains about which treatment performs best in patients receiving corticosteroids. OBJECTIVES To estimate probabilities of noninferiority between baricitinib and sarilumab compared to tocilizumab in patients treated with corticosteroids. DATA SOURCES PubMed, Embase, Cochrane Library, and MedRxiv. STUDY ELIGIBILITY CRITERIA Eligible RCTs assigning hospitalized adults with COVID-19 treated with corticosteroids to tocilizumab or baricitinib or sarilumab versus standard of care or placebo (control). METHODS Reviewers independently abstracted published data and assessed study quality with the Risk of Bias 2 tool. Unpublished data, if required, were requested from authors of included studies. The outcome of interest was all-cause mortality at 28 days. PARTICIPANTS Twenty-seven RCTs with 13 549 patients were included. Overall, the risk of bias was low. Bayesian pairwise meta-analyses were used to aggregate results of each treatment versus control. The average odds ratio for mortality was 0.78 (95% credible interval [CrI]: 0.65, 0.94) for tocilizumab; 0.78 (95% CrI: 0.56, 1.03) for baricitinib; and 0.91 (95% CrI: 0.60, 1.40) for sarilumab. The certainty of evidence (GRADE) ranged from moderate to low. Bayesian meta-regressions with multiple priors were used to estimate probabilities of noninferiority (margin of 13% greater effect by tocilizumab). Compared to tocilizumab, there were ≤94% and 90% probabilities of noninferiority with baricitinib and sarilumab, respectively. RESULTS All but two studies included data with only indirect evidence for the comparison of interest. CONCLUSIONS Among hospitalized COVID-19 treated with corticosteroids, there are high probabilities that both baricitinib and sarilumab are associated with similar mortality reductions in comparison to tocilizumab.

Methodological quality

Publication Type : Meta-Analysis ; Review

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