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

Due to high heterogeneity and risk of bias (RoB) found in previously published meta-analysis (MA), a concrete conclusion on the efficacy of baricitinib in reducing mortality in coronavirus disease 2019 (COVID-19) patients was unable to form. Hence, this systematic review and MA were conducted to analyse whether RoB, heterogeneity, and optimal sample size from placebo-controlled randomized 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 MA were conducted using RevMan 5.4. The grading of the articles was conducted using the GRADEPro Guideline Development Tool. Ten RCTs were included in the current systematic review. Only five low RoB articles are Phase III placebo-controlled RCTs with a high certainty level based on the GRADE grading system. For the MA, based on five low RoB articles, baricitinib statistically significantly reduced mortality where the risk ratio (RR) = 0.68 [95% confidence interval (95% CI) 0.56-0.82; P