Glucocorticoids, tocilizumab may reduce complications in COVID-19-related cytokine storm
High-dose methylprednisolone, followed by tocilizumab if needed, may speed up respiratory recovery, decrease hospital mortality and prevent ventilation in patients with COVID-19-related cytokine storm syndrome, said researchers.
“Cytokine storm syndrome (CSS) has been increasingly more recognized as a complication of COVID-19 disease,” Sofia Ramiro, MD, PhD, of the Zuyderland Medical Center, in the Netherlands, told Healio Rheumatology. “Untreated, it has a very high mortality of up to 40%. It was, therefore, important to investigate the effect of different treatment strategies in this specific group. Furthermore, given the hyperinflammatory state of the CSS there was a strong rationale to treat patients with an immunosuppressive strategy.”
To examine whether intensive glucocorticoids, with or without tocilizumab (Actemra, Genentech), compared with supportive care only, could reduce mortality and prevent the need for ventilation among patients with COVID-19-associated cytokine storm syndrome, Ramiro and colleagues at the Zuyderland Medical Center began an experimental treatment strategy. Beginning April 1, 86 patients with COVID-19-associated cytokine storm syndrome received high-dose intravenous methylprednisolone for 5 consecutive days. Specifically, this regimen included 250mg on day 1 followed by 80mg on days 2-5.
Later, if respiratory conditions failed to improve sufficiently, researchers added a single 8 mg/kg infusion of tocilizumab on or after day 2. Data on 86 control patients with COVID-19-associated cytokine storm syndrome were retrospectively analyzed from a pool of 350 individuals admitted between March 7 and March 31. These patients were matched 1-to-1 with those in the treatment group based on age and sex. The primary outcome was two or more stages of improvement on a seven-item WHO-endorsed scale for severe influenza pneumonia trials, or hospital discharge. The secondary outcomes were hospital mortality and ventilation.
According to the researchers, patients in the treatment group demonstrated a 79% greater likelihood of reaching the primary outcome (HR = 1.8; 95% CI, 1.2-2.7) 7 days earlier, compared with those in the control group, who received supportive care only. Those in the treatment group also enjoyed 65% less mortality (HR = 0.35; 95%CI, 0.19-0.65) and 71% less invasive mechanical ventilation (HR = 0.29; 95%CI, 0.14-0.65). These effects remained constant following confounding and sensitivity analyses.
“A strategy involving a course of high-dose glucocorticoids, followed by tocilizumab if needed, has shown to accelerate respiratory recovery, lower hospital mortality and reduce the likelihood of invasive mechanical ventilation compared with supportive care only in COVID-19-associated CSS,” Ramiro said. “CSS should be recognized and considered as a treatable complication of COVID-19 and immunosuppressive treatment should be started timely. A treatment with high-dose glucocorticoids is a convenient choice since glucocorticoids are safe, widely available and inexpensive.”