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Compared with placebo, this Janus kinase inhibitor was associated with lower risk for death or respiratory failure in such patients.
In patients hospitalized with COVID-19, excess inflammation generally underlies clinical progression. By reducing cytokine production, Janus kinase (Jak) inhibitors tamp down inflammation. Now, investigators report results of an industry-supported trial of the Jak inhibitor tofacitinib in 289 patients in Brazil with COVID-19 pneumonia. Participants had been hospitalized for <72 hours and did not require mechanical ventilation or extracorporeal membrane oxygenation. At enrollment, 75% were receiving supplemental oxygen and 78% were receiving glucocorticoids. All were randomized 1:1 to tofacitinib or placebo; median time from onset of symptoms to randomization was 10 days.
Progression to death or respiratory failure occurred significantly less often with tofacitinib than placebo (18% vs. 29%; risk ratio, 0.63). Death from any cause and clinical status on an ordinal scale were more favorable in the tofacitinib group, but these differences were not statistically significant. Rates of serious infections or thromboembolic events were similar in both groups.
Accumulating evidence shows that adding Jak inhibitors to corticosteroids improves outcomes in hospitalized patients receiving supplemental oxygen but not requiring mechanical ventilation. The NIH and the Infectious Diseases Society of America both endorse use of the Jak inhibitor baricitinib in selected hospitalized patients. Tocilizumab, an interleukin-6 (IL-6) inhibitor, is recommended for similar patients (but not in combination with a Jak inhibitor until more is known about potential toxicities). For a patient recently hospitalized with COVID-19 who has an escalating oxygen requirement, elevated inflammatory markers, and rapid progression toward needing high-flow noninvasive or invasive mechanical ventilation, I would give a combination of dexamethasone (with remdesivir) plus either tocilizumab or a Jak inhibitor. We don’t yet know whether a Jak inhibitor or an IL-6 inhibitor would be better here; future trials should address this key question.
Créditos: Comité científico Covid