Glucocorticoids Plus Tocilizumab May Improve Respiratory Outcomes in COVID-19-Related Cytokine Storm Syndrome

Treatment with glucocorticoids and tocilizumab may accelerate respiratory recovery and reduce in-hospital mortality and the likelihood of mechanical ventilation in patients with coronavirus disease 2019 (COVID-19)-associated cytokine storm syndrome (CSS), according to study results published in Annals of the Rheumatic Diseases.

Systemic hyperinflammation in patients with COVID-19-associated pneumonia is associated with significant morbidity and mortality. In the COVID High-Intensity Immunosuppression in Cytokine Storm Syndrome (CHIC) study, clinicians at the Zuyderland Medical Center in South Limburg, Netherlands, performed a historically-matched observational study to determine if immunosuppressive treatment vs supportive care alone could improve outcomes in patients with COVID-19-associated CSS.

Patients with COVID-19-associated CSS (n=86; 79% men) received treatment with intravenous methylprednisolone followed by interleukin-6 receptor blocker tocilizumab. Patients were matched 1:1 with a historic control population who received supportive care only.

The primary outcome of the study was hospital discharge or improvement of at least 2 stages on a 7-point scale, which included hospitalization status, activity status, oxygen requirements, and death.

Compared with patients in the control group, those in the treatment group were 79% more likely to achieve 2-stage improvement in respiratory status (hazard ratio [HR], 1.79; 95% CI, 1.20-2.67). This improvement was reached by a median of 7 days, before patients were discharged from the hospital. The effect size was larger in patients with elevated serum ferritin levels (>1419 µg/L) than those with lower serum ferritin levels (HR, 2.7 vs 1.6, respectively). At days 7 and 14, stage scores were better in the treatment vs control group (P <.0001 for both).

In-hospital mortality was 65% lower in the treatment group than in the control group (HR, 0.35; 95% CI, 0.19-0.65). At hospital day 14, the mortality rate in the treatment group was 11.6% compared with 38.4% in the control group (P <.0001). The likelihood of requiring mechanical ventilation was 71% lower in the treatment than control group (HR, 0.29; 95% CI, 0.14-0.60). The daily incidence of new mechanical ventilations was 1.3% vs 5.4% in the treatment vs control group, respectively (P =.0003). The duration of mechanical ventilation was similar between groups.

Pulmonary embolism occurred more frequently in the treatment than control group; however arrhythmias were less frequent in the treatment group, but neither of these trends were significant. 

Researchers acknowledged that a randomized controlled trial would have been ideal, but noted that clinicians were uncomfortable randomly assigning patients to receive standard care only, which was clearly insufficient.

“[W]e have shown here that a strategy involving a course of high-dose [methylprednisone], followed by [tocilizumab] in case of insufficient improvement, may accelerate respiratory recovery, lower hospital mortality and reduce the likelihood of invasive mechanical ventilation in COVID-19-associated CSS,” the researchers concluded. “CSS should be [recognized] and considered as a treatable complication of COVID-19 and immunosuppressive treatment should be started timely.”

Disclosures: Several authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.

Reference

Ramiro S, Mostard RLM, Magro-Checa C, et al. Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study [published July 20, 2020]. Ann Rheum Dis. doi:10.1136/annrheumdis-2020-218479