Janus kinases inhibitors for coronavirus disease-2019: A pairwise and Bayesian network meta-analysis

BACKGROUND: JAK (Janus kinases) inhibitors have been proposed as a promising treatment option for the coronavirus disease-2019 (COVID-19). However, the benefits of JAK inhibitors and the optimum thereof for COVID-19 have not been adequately defined. METHODS: Databases were searched from their inception dates to 17 June 2022. Eligible studies included randomized controlled trials and observational studies. Extracted data were analyzed by pairwise and network meta-analysis. The primary outcome was the coefficient of mortality. RESULTS: Twenty-eight studies of 8,206 patients were included and assessed qualitatively (modified Jadad and Newcastle–Ottawa Scale scores). A pairwise meta-analysis revealed that JAK inhibitors effectively reduced the mortality (OR = 0.54; 95% CI: 0.46–0.63; P < 0.00001; I(2) = 32%) without increasing the risk of adverse events (OR = 1.02; 95% CI: 0.88–1.18; P = 0.79; I(2) = 12%). In a network meta-analysis, clinical efficacy benefits were seen among different types of JAK inhibitors (baricitinib, ruxolitinib, and tofacitinib) without the observation of a declined incidence of adverse events. The assessment of rank probabilities indicated that ruxolitinib presented the greatest likelihood of benefits regarding mortality and adverse events. CONCLUSION: JAK inhibitors appear to be a promising treatment for COVID-19 concerning reducing mortality, and they do not increase the risk of adverse events vs. standard of care. A network meta-analysis suggests that mortality benefits are associated with specific JAK inhibitors, and among these, ruxolitinib presents the greatest likelihood of having benefits for mortality and adverse events. SYSTEMATIC REVIEW REGISTRATION: [www.crd.york.ac.uk/prospero], identifier [CRD42022343338].