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

Jianyi Niu; Zhiwei Lin; Zhenfeng He; Xiaojing Yang; Lijie Qin; Shengchuan Feng; Lili Guan; Luqian Zhou; Rongchang Chen

doi:10.3389/fmed.2022.973688

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

Front Med (Lausanne). 2022 Nov 23:9:973688. doi: 10.3389/fmed.2022.973688. eCollection 2022.

Authors

Jianyi Niu^{1

2}, Zhiwei Lin^{1

2}, Zhenfeng He^{1

2}, Xiaojing Yang^{1

2}, Lijie Qin^{1

2}, Shengchuan Feng^{1

2}, Lili Guan^{1

2}, Luqian Zhou^{1

2}, Rongchang Chen^{1

2

3}

Affiliations

¹ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
² Respiratory Mechanics Laboratory, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
³ Key Laboratory of Shenzhen Respiratory Diseases, Institute of Shenzhen Respiratory Diseases, Shenzhen People's Hospital (The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University), Shenzhen, Guangdong, China.

Abstract

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].

Keywords: COVID-19; JAK inhibitors; adverse events; mortality; network meta-analysis.

Publication types

Systematic Review