Corticosteroids plus tocilizumab superior to standard of care in COVID-19 cytokine storm
Corticosteroids plus tocilizumab demonstrated superior survival outcomes compared with standard or care and corticosteroids alone, or alongside anakinra, in patients with COVID-19 cytokine storm, according to data published in Chest.
“Uncontrolled and unabated cytokine release and a hyperinflammatory response termed as COVID-19 ‘cytokine storm’ (CCS), was described as a major determinant of poor survival,” Sonali Narain, MBBS, of the Barbara Zucker School of Medicine at Hofstra University and Northwell Health, and colleagues wrote. “Limited data existed to guide clinical decision-making in the absence of FDA-approved COVID-19 specific therapies. Faced with rapidly increasing rates of infection and hospitalizations, physicians repurposed immunomodulatory treatments in an attempt to curtail morbidity and mortality.”
To examine whether immunomodulatory therapies improve survival among patients with COVID-19 cytokine storm, Narain and colleagues conducted a retrospective analysis of electronic health records across the Northwell Health system, based in Great Neck, New York. In all, the researchers included 5,776 patients with COVID-19 hospitalized between March 1 and April 24. Cytokine storm was defined through inflammatory markers — ferritin levels greater than 700 ng/mL, C-reactive protein of more than 30 mg/dL or lactate dehydrogenase levels of more than 300 U/L.
All included patients were categorized into one of six groups. These included one standard of care group, defined as those who received no immunomodulatory treatment, and five groups in which participants received either corticosteroids, tocilizumab (Actemra, Genentech) or anakinra (Kineret, SOBI) alone or in combination with corticosteroids. The primary outcome was hospital mortality.
According to the researchers, patients treated with corticosteroids plus tocilizumab demonstrated lower mortality compared to those who received standard of care (HR = 0.44; 95% CI, 0.35-0.55). The tocilizumab-corticosteroids combination also resulted in survival outcomes that were superior to corticosteroids alone (HR = 0.66; 95% CI, 0.53-0.83), as well as corticosteroids plus anakinra (HR = 0.64; 95% CI, 0.50-0.81).
Meanwhile, corticosteroids, either alone (HR = 0.66; 95% CI, 0.57-0.76) or in combination with tocilizumab (HR = 0.43; 95% CI, 0.35-0.55) or anakinra (HR = 0.68; 95% C, :0.57-0.81) improved hospital survival compared with standard of care.
“The use of immunomodulatory drugs decreases mortality in the population of COVID-19 patients with evidence of hyperinflammatory response,” Narain told Healio Rheumatology. “The decreased mortality was especially seen in those receiving tocilizumab plus steroids when compared to no steroids, but even when compared to the group who received steroids alone. This role for combinations of immunomodulatory therapies needs to be elucidated in prospective clinical trials comparing combinations to steroids alone.
“Our study supports the RCT findings that steroids decrease mortality in severe COVID-19 patients who require oxygen supplementation,” she added. “Our study focused on patients with laboratory evidence of hyperinflammatory response. In addition, our study points to the likelihood of a further decrease in mortality with the addition of tocilizumab with steroids. This needs to be elucidated in an RCT comparing combination immunomodulatory therapies versus just steroids for COVID-19 patients with evidence of hyperinflammation.”