Approved JAK inhibitor baricitinib shows promise against cytokine storm in COVID-19 clinical study

November 13, 2020

A clinical study involving 601 patients in Italy and Spain suggests that the JAK inhibitor drug baricitinib may enhance survival rates of patients with severe COVID-19, primarily by blunting the runaway immune inflammation known as "cytokine storm." While the authors are careful to note that their study was not a fully randomized trial with a placebo control group, the drug nonetheless had a notable effect, particularly in the Spanish treatment cohort, composed entirely of elderly patients over the age of 70. This suggests the treatment could address high rates of COVID-19 morbidity and mortality observed in this demographic worldwide. Further in vitro experiments in liver cell spheroids suggest the drug may also restrain abnormally high expression of the ACE2 receptor - required for entry of the SARS-CoV-2 virus - in these cells, helping to reduce viral infection of the liver, and likely other organs and tissues that do not normally express high levels of the ACE2 receptor. Using AI-based analyses, Justin Stebbing and colleagues had previously identified baricitinib, approved for the treatment of rheumatoid arthritis, as a promising treatment for COVID-19. They also previously found that the drug can reduce levels of the pro-inflammatory cytokine IL-6 in rheumatoid arthritis patients. Noting that levels of IL-6 have been reported to correlate with symptom severity in patients with COVID-19, Stebbing et al. enrolled a total of 179 hospitalized patients from Pisa, Italy, and 422 from Albacete, Spain. In the Pisa cohort, 37 patients were given baricitinib once daily for two weeks; of the 142 controls, 37 were matched with the drug recipient group using a "propensity score" based on the patients' age, sex, and several parameters related to their medical history. In Albacete, 46 patients were given a lower dose of the drug for shorter periods of time, due to safety considerations in this elderly cohort. As in Pisa, 46 of the 376 control patients were matched with the drug recipient cohort using the propensity score method. Overall, across both cohorts matched by propensity score, the patients who received baricitinib either died or received invasive mechanical ventilation at roughly half the rate (16.9%) of the untreated group (34.9%). Stebbing et al. note that randomized trials of the drug are currently underway. Based on their own results - including their additional experiments in liver cell spheroids - the authors note that they "eagerly await" the results of these trials.
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American Association for the Advancement of Science

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