Author: Denise Baez
Among hospitalised patients with coronavirus disease 2019 (COVID-19)-related cytokine storm, the combination of corticosteroids and tocilizumab was associated with superior survival outcomes versus standard of care and corticosteroids, alone or in combination with anakinra, according to a study published in CHEST.
In addition, “corticosteroid use either alone or in combination with tocilizumab or anakinra was associated with reduced hospital mortality compared with standard of care,” reported Dimitre G. Stefanov, PhD, Northwell Health, Manhasset, New York, and colleagues.
The findings come from a retrospective analysis of electronic health records of 5,776 patients with COVID-19 who were hospitalised between March 1, 2020, and April 24, 2020, across 12 hospitals that comprise the Northwell Health system in New York. All patients experienced COVID-19 related cytokine storm — defined as having ferritin levels >700ng/mL, C-reactive protein levels >30mg/dL or lactate dehydrogenase levels >300U/L.
Patients most frequently met criteria with high lactate dehydrogenase (76.2%) alone or in combination, followed by ferritin (63.2%) and C-reactive protein (8.4%). More than 80% of patients had an elevated D-dimer.
Patients were stratified according to type of immunomodulatory treatment they received while hospitalised: (1) standard of care only (n = 3,076; median age, 64.6 years); (2) corticosteroids only (n = 1,383; median age, 66.5 years); (3) corticosteroids plus tocilizumab (n = 454; median age, 64.5 years); (4) corticosteroids plus anakinra (n = 733; median age 65.7 years); (5) tocilizumab only (n = 73; median age, 62.4 years); and (6) anakinra only (n = 57; median age, 66.7 years). More than half of patients in each group were male (61.5%, 64.6%, 72.9%, 67.5%, 71.2%, and 66.7%, respectively).
In the timeframe of the analysis, hydroxychloroquine, azithromycin, colchicine, and vitamin C, either alone or in combination, were administered to all patients with COVID-19 as part of institutional protocols.
Patients treated with corticosteroids and tocilizumab had a 56% reduced mortality risk compared with patients who received standard of care alone (hazard ratio [HR] = 0.44; 95% confidence interval [CI], 0.35-0.55; P < .0001), a 34% reduced mortality risk compared with patients who received corticosteroids alone (HR = 0.66; 95% CI, 0.53-0.83; P = .004), and a 36% reduced mortality risk compared with patients who received corticosteroids plus anakinra (HR = 0.64; 95% CI, 0.50-0.81; P = .003).
“This association remained after controlling for covariates that influence mortality in COVID-19,” the authors noted.
Compared with standard of care, improved survival was seen for patients who received corticosteroids alone (HR = 0.66; 95% CI, 0.57-0.76; P< .0001), or in combination with tocilizumab (HR = 0.44; 95% CI, 0.35-0.55; P< .0001) or anakinra (HR = 0.68; 95% CI, 0.57-0.81; P< .0001).
There were increased rates of bacteremia and fungemia in the steroid groups compared with standard of care; however, despite this increase in the infection rate, improved survival remained in these cohorts.
“Our study is the largest retrospective analysis to date reporting on outcomes comparing the use of immunomodulatory therapies such as corticosteroids, tocilizumab, and anakinra in the treatment of COVID-19 cytokine storm,” the authors wrote. “Our findings suggest that patients receiving steroids and tocilizumab had the lowest mortality of all treatment groups. Corticosteroid use, either alone or in combination with tocilizumab or anakinra, was associated with lower hospital mortality compared with standard of care. A randomised clinical trial with head-to-head comparison of tocilizumab plus corticosteroids versus corticosteroids alone is warranted. Further investigation into the effect of dosing and timing of these drugs also needs to be elucidated.”