Acute respiratory distress syndrome (ARDS) is a severe complication of COVID-19. It is associated with a high mortality rate, especially in older patients and those with pulmonary and other comorbidities.
In a non-randomized prospective phase II multicenter study, we tested whether treatment with ruxolitinib could improve the outcome of COVID-19 ARDS requiring invasive mechanical ventilation. We found that ruxolitinib improved outcomes reduced the need for supportive oxygen, and normalized lymphocyte counts and inflammatory markers.
Efficacy
Ruxolitinib is a first-in-class JAK1 and JAK2 inhibitor approved in the United States for treating steroid-refractory acute graft versus host disease (GRHD), polycythemia vera (PV), and myelofibrosis. It is also being studied in COVID-19-associated ARDS.
In patients with COVID-19, the onset of respiratory symptoms can be rapid and severe. Approximately 20% of people develop pneumonia, require hospitalization, and require oxygen support; 5% require admission to the intensive care unit (ICU) or invasive mechanical ventilation.
Acute respiratory distress syndrome (ARDS) is a life-threatening inflammatory lung condition that occurs when the body is not able to fight off inflammation. This can lead to severe respiratory failure and death if left untreated.
A study evaluating ruxolitinib in patients with COVID-19-associated ARDS found that it was effective in improving 28-day survival. However, the results were not statistically significant. This may be due to differences in study design and regional differences, including differences in how patients are treated. A larger sample is needed to determine whether trends toward increased efficacy in patient subgroups are clinically significant.
Safety
Ruxolitinib is safe and well tolerated when used for COVID-19-associated ARDS. It improves pulmonary function and reduces the need for oxygen.
Pirfenidone (ruxolitinib) is a phosphodiesterase 5 (PDE5) inhibitor that works by blocking the interaction between IL-6 and soluble IL-6 receptors. This is important because IL-6 can lead to a cytokine storm and eventually cause ARDS in patients with a severe COVID-19 infection.
The safety of ruxolitinib has been demonstrated in a phase 3 trial (RUXCOVID) conducted in 61 centers worldwide. The randomized, double-blind, placebo-controlled study compared ruxolitinib with the standard of care in 424 patients with COVID-19-associated ARDS. The trial was approved by the ethics committee at each participating institution and was conducted in compliance with the Declaration of Helsinki.
Tolerability
Ruxolitinib is a safe and effective medication for treating patients with myelofibrosis, polycythemia vera (PV), and steroid-refractory acute graft-versus-host disease. It is in the Janus kinase inhibitor class of medications.
Inhibits the signaling of Janus kinases 1 and 2 by blocking STAT3 phosphorylation in response to pro-inflammatory cytokines. Inhibition of the JAK/STAT pathway is associated with a reduction in inflammatory mediators, which has a positive effect on lung function and quality of life.
The medication is also used to treat a condition called granulomatous vasculitis, which can occur in people with myelofibrosis or PV who are not responding to other therapies. It is given by mouth, usually twice a day, to patients who are taking other medications.
The medication is also being tested for the prevention and treatment of respiratory failure caused by COVID-19-associated ARDS. It is being investigated in a clinical trial in hospitalized patients with COVID-19-associated ARDS requiring mechanical ventilation. It is available to eligible patients in the United States via an Expanded Access Program.
Adverse Events
Ruxolitinib is a Janus kinase (JAK) 1 and JAK2 inhibitor that has been shown to improve recovery time and 28-day mortality in patients with COVID-19-associated ARDS who require mechanical ventilation. This was a phase 3 randomized, double-blind, placebo-controlled trial.
In this study, 281 nonmechanically ventilated hospitalized patients with severe COVID-19-associated ARDS were randomly assigned to receive ruxolitinib 15 mg twice daily or matching dual-dose placebo tablets for 14 days. The trial was terminated early because it was underpowered to meet its primary endpoint.
The most common treatment-emergent adverse events were headaches and diarrhea. Grade 3 or more serious adverse events were more common in the ruxolitinib group. In addition, a high proportion of patients had a viral relapse or worsened disease after therapy. This may be a result of the derangement of the immune system in COVID-19-related ARDS, known as the cytokine storm. This condition involves an increase in the levels of cytokines such as interleukin (IL)-1b, IL-2, IL-6, and IL-10.