Clin Microbiol Infect. 2022 Jul 18:S1198-743X(22)00372-X. doi: 10.1016/j.cmi.2022.07.008. Online ahead of print.
ABSTRACT
BACKGROUND: Randomized controlled trials [RCT] established the mortality reduction by tocilizumab, baricitinib and sarilumab in hospitalized COVID-19 patients. However, uncertainty remains about which treatment performs best in patients receiving corticosteroids.
OBJECTIVE: 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 SELECTION: Eligible RCTs assigning hospitalized adults with COVID-19 treated with corticosteroids to tocilizumab or baricitinib or sarilumab vs. standard of care or placebo (control).
DATA EXTRACTION: 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 Unpublished data, if required, were requested from authors of included studies.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.
DATA SYNTHESIS: 27 RCTs with 13549 patients were included. Overall, the risk of bias was low. Bayesian pairwise meta-analyses were used to aggregate results of each treatment vs. 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 up to 94 % and 90 % probabilities of noninferiority with baricitinib and sarilumab, respectively.
LIMITATIONS: All but 2 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.
PMID:35863630 | PMC:PMC9293401 | DOI:10.1016/j.cmi.2022.07.008