Acalabrutinib - New option to calm cytokine storm in severe Covid 19
As the Covid 19 pandemic is progressing new and new drugs are being tried to contain the severity of the disease.
Dr Mark Roschewski and colleagues have found that acalabrutinib may help calm cytokine storm in severe COVID-19 patients.
The drug acalabrutinib is FDA-approved treatment for several types of B cell cancers.
The drug improved the oxygenation levels and decreased molecular markers of inflammation in a majority of 19 patients hospitalized for the treatment of severe COVID-19. The study has been published in the journal Science Immunology.
A hyperactive immune response isn't unique to COVID-19. People with autoimmune diseases and cancer patients receiving immunotherapy can experience similar symptoms. These responses are referred to as macrophage activation syndrome, cytokine release syndrome -- or simply "cytokine storms."
Acalabrutinib was administered to 11 patients on supplemental oxygen and 8 patients on mechanical ventilation over a 10-to-14-day course of treatment.
At the end of treatment, 8 of 11 patients on supplemental oxygen were breathing room air, and 4 of 8 patients on ventilation were extubated, with 2 of the 8 breathing room air. Measurements of two proteins related to inflammation decreased in the majority of patients, with no signs of toxicity from the drug.
The study is not a clinical trial, but rather an off-label observational study to see if acalabrutinib could help dampen the massive immune response - sometimes called a "cytokine storm" - that is associated with the most severe cases of COVID-19.
Acalabrutinib inhibits the Bruton tyrosine kinase (BTK) protein, which aids immune cells called macrophages in activating a variety of other proteins in the body's innate immune response. Patients with severe COVID-19 have a hyperinflammatory immune response that appears to be driven by macrophage activation, leading to acute respiratory distress syndrome (ARDS) and often death.
Roschewski et al. also studied BTK activation and immune markers in whole blood from 4 COVID-19 patients and 5 healthy individuals. BTK activation levels and the presence of the inflammatory protein IL-6 were higher in the COVID-19 patients, further suggesting that BTK may play a critical role in the disease's progression.
An international prospective randomized controlled clinical trial is now underway to confirm the safety and efficacy of this BTK inhibitor as a therapeutic strategy against COVID-19, the authors note.
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