Acute respiratory distress syndrome (ARDS) is a severe COVID-19 side effect. It is associated with a high mortality rate, particularly in older individuals and those with pulmonary and other comorbidities. We examined whether ruxolitinib therapy could improve the outcome of COVID-19 ARDS patients requiring invasive mechanical ventilation in a non-randomized prospective phase II multicenter study.
Our findings show that ruxolitinib improves outcomes, reduces the need for oxygen treatment, and restores normal lymphocyte counts and inflammatory markers. Roxolitinib, a first-in-class JAK1 and JAK2 inhibitor, has been approved in the United States for the treatment of myelofibrosis, polycythemia vera, and acute graft versus host disease (GRHD) refractory to steroids. Furthermore, it is being studied in ARDS in conjunction with COVID-19.
In COVID-19 patients, the onset of respiratory symptoms can be sudden and severe. 20% of pneumonia patients require hospitalization, oxygen support, and invasive artificial ventilation; 5% require intensive care unit (ICU) admission. A life-threatening lung condition known as acute respiratory distress syndrome (ARDS) develops when the body is unable to control inflammation. If left untreated, this can lead to severe respiratory failure and mortality. According to one study, ruxolitinib substantially improved 28-day survival in patients with COVID-19-induced ARDS.
However, the results were not statistically significant. This could be due to differences in study design and regional variations, such as differences in patient care. A larger sample size is needed to determine whether clinically significant trends toward greater efficacy in patient subgroups exist. Ruxolitinib, when used to treat COVID-19-related ARDS, improves pulmonary function and reduces the need for oxygen while remaining secure and well tolerated. Pirfenidone (ruxolitinib) inhibits IL-6 interaction with soluble IL-6 receptors by working as a PDE5 inhibitor.
This is important because IL-6 can cause a cytokine storm in people with severe COVID-19 infection, leading to ARDS. Ruxolitinib's safety was demonstrated in a phase 3 study (RUXCOVID) conducted in 61 locations around the world. The trial, which compared ruxolitinib to the standard of care in 424 patients with COVID-19-associated ARDS, was approved by the ethics committees at each participating institution and carried out in accordance with the Declaration of Helsinki.
Roxolitinib is a safe and dependable drug for the therapy of myelofibrosis, polycythemia vera (PV), and steroid-refractory acute graft-versus-host disease. It refers to a class of drugs known as Janus kinase inhibitors. STAT3 phosphorylation is blocked in response to pro-inflammatory cytokines, blocking Janus kinase 1 and 2 signaling. A reduction in inflammatory mediators is related to JAK/STAT pathway inhibition, which improves lung function and quality of life. Furthermore, the drug is used to treat granulomatous vasculitis, a condition that can occur in people who have PV or myelofibrosis and are not responding to other treatments. It is usually given orally twice daily to patients who are taking other medications.
The drug is being tested for the prevention and treatment of respiratory failure caused by COVID-19-associated ARDS in a clinical study involving hospitalized COVID-19-associated ARDS patients who require mechanical ventilation. It is available to qualified individuals in the United States through an expanded access program. The Janus kinase (JAK) 1 and JAK2 inhibitor roxolitinib enhanced recovery times and 28-day mortality in patients with COVID-19-associated ARDS who required artificial breathing. This research employed a phase III randomized, double-blind, placebo-controlled experiment. The trial was stopped early due to insufficient ability to accomplish its primary endpoint.
Roxolitinib 15 mg twice daily or corresponding dual-dose placebo tablets were given at random to 281 nonmechanically ventilated hospitalized patients with severe COVID-19-associated ARDS for 14 days. The most common side effects that emerged during therapy were headache and diarrhea. More severe adverse events (grade 3 or higher) occurred more commonly in the ruxolitinib group. Following treatment, a significant percentage of people reported a viral relapse or worsening of their condition. This could be due to the cytokine storm, an immune system imbalance seen in COVID-19-induced ARDS. This illness causes an increase in the levels of cytokines such as interleukin (IL)-1b, IL-2, IL-6, and IL-10.
