Abstract
Coronavirus disease-2019 (COVID-19) represents a global public health nightmare. The “cytokine storm,” the most prominent underlying pathophysiologic mechanism of this disease, can theoretically be targeted at several stages. Janus kinase (JAK) inhibitors constitute a drug class that could ameliorate the inflammatory response and enhance antibody production. Herein, we aimed to evaluate the efficacy of JAK inhibitors in patients with COVID-19, performing the most updated relevant meta-analysis. We searched two major databases for randomized controlled trials (RCTs) enrolling adult patients with documented COVID-19 in the in-hospital setting, assigned either to JAK inhibitor treatment plus standard of care or standard of care alone. We set as primary efficacy outcome the endpoint of COVID-19 death on day 28 and as secondary efficacy composite outcome that of mechanical ventilation or initiation of extracorporeal membrane oxygenation (ECMO). We finally pooled data of interest from 4 RCTs in a total of 1338 subjects with documented COVID-19 infection, utilizing the following JAK inhibitors: baricitinib, ruxolitinib, tofacitinib, and nezulcitinib. Treatment with JAK inhibitor compared to control resulted in a significant reduction in the risk for COVID-19 death by 43%, while it also led to a significant decrease in the risk for mechanical ventilation or ECMO initiation by 36%. Herein, we demonstrate a clear benefit with JAK inhibitors added to standard of care in patients with COVID-19 in terms of risk reduction concerning major outcomes. Larger RCTs will elucidate their place in treatment armamentarium against COVID-19.
Keywords: COVID-19; Janus kinase inhibitor; Mechanical ventilation; Mortality.
【저자키워드】 COVID-19, mechanical ventilation, mortality., Janus kinase inhibitor, 【초록키워드】 Randomized controlled trial, Treatment, coronavirus disease, Meta-analysis, Efficacy, Baricitinib, Cytokine storm, Randomized controlled trials, mechanical ventilation, risk, outcome, database, RCT, coronavirus disease-2019, outcomes, extracorporeal membrane oxygenation, COVID-19 infection, Patient, death, ECMO, ruxolitinib, jak inhibitors, inhibitor, disease, Jak, mechanism, JAK inhibitor, RCTs, Kinase inhibitor, Tofacitinib, Inflammatory response, Janus kinase, antibody production, Standard of care, In-hospital, Endpoint, nezulcitinib, stages, subject, global public health, Adult patients, janus, significant decrease, risk reduction, benefit, ENhance, evaluate, added, searched, assigned, reduction in, concerning, Mechanical, nightmare, pathophysiologic, patients with COVID-19, 【제목키워드】 Randomized controlled trial, Meta-analysis,