Promising results with glucocorticoids, tocilizumab for COVID-19-associated cytokine storm syndrome
medwireNews: Treatment with high-dose methylprednisolone, followed by the interleukin (IL)-6 inhibitor tocilizumab if needed, may improve outcomes for patients with COVID-19 and cytokine storm syndrome (CSS), suggest findings from the CHIC study published in the Annals of the Rheumatic Diseases.
CSS “is an important complication” occurring in up to a quarter of patients with SARS-CoV-2 infection, and is “often responsible for a fatal outcome,” say the study authors, led by rheumatologist Sofia Ramiro (Zuyderland Medical Center, Heerlen, the Netherlands).
EULAR explains in a press release that “[r]heumatologists were involved in this study because of their expertise in immunosuppressive treatment, as advised in recent EULAR Recommendations.”
The CHIC study included 86 patients hospitalized at the Zuyderland Medical Center with COVID-19 and CSS – defined as rapid respiratory deterioration plus elevated levels of two or more biomarkers (C-reactive protein >100 mg/L, ferritin >900 μg/L, and/or D-dimer >1500 μg/L) – who were treated with intravenous methylprednisolone 250 mg on day 1 followed by 80 mg on days 2–5, with an optional 2-day extension. The 37 patients who did not experience clinical improvement or had worsening respiratory status were also given a single infusion of tocilizumab 8 mg/kg between day 2 and day 5.
The outcomes of these patients were compared with those from a historic cohort of 86 age- and sex-matched patients with COVID-19-associated CSS who were treated at the same center. Across both groups, all patients except one also received antibiotic treatment according to local protocol, and 77–79% were given chloroquine.
Ramiro and team found that patients in the glucocorticoids/tocilizumab group were significantly more likely than those in the control group to achieve the primary composite outcome of discharge from hospital or an improvement in respiratory function of at least two stages on a World Health Organization-endorsed 7-point scale. Rates of the primary outcome were 74.4% and 51.2%, respectively, with a hazard ratio (HR) of 2.31 after adjustment for factors including BMI, smoking, and comorbidities.
Similarly, rates of in-hospital mortality (16.3 vs 47.7%) and mechanical ventilation (11.6 vs 27.9%) were significantly lower in the treatment compared with the control arm, with corresponding adjusted HRs of 0.26 and 0.22.
These findings remained consistent in sensitivity analyses excluding patients on mechanical ventilation at baseline, those treated with tocilizumab, or patients aged under 50 or at least 80 years.
Ramiro et al say that despite concerns about treating critically ill COVID-19 patients with glucocorticoids, “patients in the CHIC study tolerated the immunosuppressive therapy remarkably well and we did not find evidence for impaired viral clearance nor for bacterial superinfection.” However, they note that longer follow-up “is needed to give final resolution about the safety and efficacy of the strategy.”
Writing in the press release, study co-author Robert Landewé said: “Our study shows that the sickest COVID-19 patients, namely those with signs of cytokine storm, had a dramatic beneficial effect on glucocorticoids.
“This appears to be one of the contrasting points of our studies compared with others, namely that we have only treated cases with signs of cytokine storm [with glucocorticoids], and not all COVID19-patients.”
medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature Group
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