Baricitinib statistically significantly reduced COVID-19 related mortality: a systematic review and Meta-Analysis of five phase III randomised, blinded and placebo controlled clinical trials

Abstract

Due to high heterogeneity and risk of bias (RoB) found in previously published meta-analysis, a concrete conclusion on the efficacy of baricitinib in reducing mortality in COVID-19 patients was unable to form. Hence, this systematic-review and meta-analysis was conducted to analyse whether RoB, heterogeneity and optimal sample size from placebo controlled randomised controlled trials (RCTs) are still the problems to derive a concrete conclusion. Search engines PubMed/MEDLINE, ScienceDirect and other sources like preprints and reference lists were searched with appropriate keywords. The RoB and meta-analysis were conducted using RevMan 5.4. The grading of the articles was conducted using the GRADEPro Guideline Development Tool. Ten (10) RCTs were included in the current systematic-review. Only 5 low RoB articles are Phase III placebo controlled RCTs with high certainty level based on the GRADE grading system. For meta-analysis, based on 5 low RoB articles, baricitinib statistically significantly reduced mortality where the risk ratio (RR) = 0.68 [95% CI: 0.56 to 0.82; p < 0.0001; I2 = 0%; p = 0.85]. The absolute mortality effect (95% CI) based on the grading system was 35 fewer mortalities per 1000 COVID-19 patients where in the baricitinib and control groups the mortality was 7.4% and 10.9%, respectively. With the presence of optimal sample size of 3944 from 5 low RoB-placebo controlled RCTs which represent a minimum of 300 million population of people and with the presence of 0% of heterogeneity from meta-analysis, the effectiveness of baricitinib in reducing the mortality in COVID-19 patients is concretely proven.