Effect of JAK Inhibitors on the Risk of Death in Patients with Moderate to Severe COVID-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

BACKGROUND: The pathophysiology of COVID-19 involves a signalling pathway based on the Janus kinases (JAKs) and the signal transducer and activator of transcription (STAT) family of proteins. As such, there has been growing interest in exploring JAK inhibitors as potential therapeutic agents for this disease.

OBJECTIVE: To provide a comprehensive summary of the efficacy of JAK inhibitors in the treatment of COVID-19 through a systematic review and meta-analysis.

DATA SOURCES: A systematic literature search was conducted in multiple electronic databases (PubMed, Scopus, and the Cochrane Central Register of Controlled Trials) and preprint repositories, without language restrictions, to identify relevant studies published up to December 31, 2023.

STUDY SELECTION AND DATA EXTRACTION: The primary outcome of interest was all-cause mortality. Randomized controlled trials (RCTs) investigating the administration of JAK inhibitors in patients with COVID-19 were included.

DATA SYNTHESIS: Through the systematic literature search, a total of 20 RCTs meeting the inclusion criteria were identified. A random-effects model was employed to estimate the pooled odds ratio for death with administration of a JAK inhibitor relative to non-administration of such an agent, with 95% confidence interval. Meta-analysis of these trials revealed a significant reduction in mortality among patients with COVID-19 who received JAK inhibitors relative to those who did not receive these agents (pooled odds ratio 0.70, 95% confidence interval 0.58-0.84).

CONCLUSIONS: The results of this systematic review and meta-analysis suggest that JAK inhibitors, specifically baricitinib, may address the urgent need for effective treatments in the ongoing COVID-19 pandemic by reducing the risk of death among affected patients. However, further research, including larger-scale RCTs, is needed to establish the efficacy and safety of other JAK inhibitors in the treatment of COVID-19 and to generate more robust evidence regarding their use in this specific patient population.