EFFECTIVENESS OF TYPE I AND TYPE III INTERFERONS AND JANUS KINASE INHIBITORS IN IMPROVING CLINICAL AND HEALTH-RELATED OUTCOMES AND THEIR SAFETY AMONG PATIENTS WITH CORONAVIRUS DISEASE 2019: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS

Abstract

Background: Presently, no purposely-developed drugs targeting coronavirus disease 2019 (COVID-19) exists. Existing studies suggest that viral dysregulation of host signalling pathway causes respiratory complications in patients. Type I Interferons (IFN-I), Type III Interferons (IFN-III) and Janus Kinase Inhibitors (JAKi), target the signalling pathway, thus facilitating clinical improvements. No review has synthesised the effectiveness and safety of these drugs on COVID-19 patients. Aim: To synthesise evidence evaluating effectiveness of IFN-I, IFN-III and JAKi against standard of care (SOC) in improving outcomes (reduced time to clinical improvement and need for ventilatory support [VS] as primary outcomes, reduced duration of hospital and intensive care units (ICU) stay, mortality as secondary outcomes) and their safety (less adverse events [AEs]) among COVID-19 patients. Design: A systematic review, network meta-analysis (NMA) and pairwise meta-analysis. Methods: PubMed, Embase, CENTRAL, Web of Science, Scopus, and CNKI were searched for randomised controlled trials examining effects of JAKi, IFN-I and IFN-III on adult COVID-19 patients in English/Chinese until January 2021. Two reviewers performed databases search, data extraction and risk of bias assessment. RStudio 1.3.1093 and RevMan 5.4 softwares were used to perform NMA and pairwise meta-analyses respectively. Results: Nine studies were included. NMA revealed JAKi was most effective in reducing time to clinical improvement, need for VS and mortality. IFN-I was most effective in reducing duration of hospital stay. Pairwise meta-analyses favoured IFN-I and JAKi over SOC in reducing all interested outcomes. Only AEs were relevant in studies using IFN-III. IFN-I, IFN-III and JAKi were safe and well-tolerated. Conclusions and Implications: Although current evidence was very uncertain about the effects and safety of IFN-I, IFN-III and JAKi on clinical and health-related outcomes in COVID-19 patients, it could suggest that IFN-I and JAKi could continue to be administered following local protocols while IFN-III should be administered with caution. Future trials for each intervention should recruit larger sample sizes and group patients according to COVID-19 severity to confirm findings.