Janus kinase inhibitors and major COVID-19 outcomes: time to forget the two faces of Janus! A meta-analysis of randomized controlled trials.
Dimitrios PatouliasMichael DoumasChristodoulos PapadopoulosAsterios KaragiannisPublished in: Clinical rheumatology (2021)
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.
Keyphrases
- coronavirus disease
- acute respiratory distress syndrome
- mechanical ventilation
- extracorporeal membrane oxygenation
- sars cov
- respiratory failure
- healthcare
- public health
- systematic review
- intensive care unit
- respiratory syndrome coronavirus
- inflammatory response
- randomized controlled trial
- quality improvement
- type diabetes
- machine learning
- clinical trial
- big data
- emergency department
- adipose tissue
- rheumatoid arthritis
- combination therapy
- chronic pain
- pain management
- drug delivery
- metabolic syndrome
- artificial intelligence
- phase iii
- global health
- lps induced