Abstract
BackgroundSevere hypoxic respiratory failure from COVID-19 pneumonia carries a high mortality risk. There is uncertainty surrounding which patients benefit from corticosteroids in combination with tocilizumab and the dosage and timing of these agents. The balance of controlling inflammation without increasing the risk of secondary infection is difficult. At present, dexamethasone 6 mg is the standard of care in COVID-19 hypoxia; whether this is the ideal choice of steroid or dosage remains to be proven.ObjectivesThe primary objective was to assess the impact on mortality of tocilizumab only, corticosteroids only, and combination therapy in patients with COVID-19 respiratory failure.MethodsA multihospital, retrospective study of adult patients with severe respiratory failure from COVID-19 who received supportive therapy, corticosteroids, tocilizumab, or combination therapy were assessed for 28-day mortality, biomarker improvement, and relative risk of infection. Propensity-matched analysis was performed between corticosteroid alone and combination therapies to further assess mortality benefit.ResultsThe steroid-only, tocilizumab-only, and combination groups showed hazard reduction in mortality at 28 days when compared with supportive therapy. In a propensity-matched analysis, the combination group (daily equivalent dexamethasone 10 mg and tocilizumab 400 mg) had an improved 28-day mortality compared with the steroid-only group (daily equivalent dexamethasone 10 mg; hazard ratio (95% CI) = 0.56 (0.38-0.84), P = 0.005] without increasing the risk of infection.Conclusion and RelevanceCombination of tocilizumab and corticosteroids was associated with improved 28-day survival when compared with corticosteroids alone. Modification of steroid dosing strategy as well as steroid type may further optimize therapeutic effect of the COVID-19 treatment.
Highlights
Initially there was hesitancy to use corticosteroids given harm demonstrated in prior outbreaks,2 the randomized evaluation of COVID-19 therapy (RECOVERY) trial demonstrated mortality benefit in COVID-19 patients who required supplemental oxygen
Multihospital cohort study of patients admitted from March 1 to June 25, 2020, to the New York University (NYU) Langone Health System to evaluate the efficacy of corticosteroids in conjunction with tocilizumab in COVID-19 patients with severe hypoxic respiratory failure
Patients were divided into 4 groups: [1] 314 patients received corticosteroids only; [2] 125 patients received tocilizumab only; [3] 223 patients received both corticosteroids and tocilizumab, and [4] 505 patients did not receive corticosteroids or tocilizumab
Summary
Mitigation of inflammation improves survival in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection resulting in COVID-19 and hypoxemia. initially there was hesitancy to use corticosteroids given harm demonstrated in prior outbreaks, the randomized evaluation of COVID-19 therapy (RECOVERY) trial demonstrated mortality benefit in COVID-19 patients who required supplemental oxygen. Given the rapid evolution of standard of care, other studies evaluating the efficacy and safety of corticosteroids in COVID-19 patients were halted. These halted studies left unanswered questions surrounding the most efficacious dose and formulation of corticosteroids.Annals of Pharmacotherapy 00(0)Nonsteroid immunomodulating pharmaceuticals have been investigated in the treatment of COVID-19 because elevation in inflammatory cytokines, including interleukin (IL)-6 and tumor necrosis factor α, was correlated with viral replication, severity of illness, and outcome, including mortality. Tocilizumab, a recombinant humanized antihuman IL-6 receptor monoclonal antibody, has been shown to have a role in the treatment of COVID-19; the optimal timing and dosage are unknown.. Given the rapid evolution of standard of care, other studies evaluating the efficacy and safety of corticosteroids in COVID-19 patients were halted.. Given the rapid evolution of standard of care, other studies evaluating the efficacy and safety of corticosteroids in COVID-19 patients were halted.4-6 These halted studies left unanswered questions surrounding the most efficacious dose and formulation of corticosteroids. Methods: A multihospital, retrospective study of adult patients with severe respiratory failure from COVID-19 who received supportive therapy, corticosteroids, tocilizumab, or combination therapy were assessed for 28-day mortality, biomarker improvement, and relative risk of infection. In a propensity-matched analysis, the combination group (daily equivalent dexamethasone 10 mg and tocilizumab 400 mg) had an improved 28-day mortality compared with the steroid-only group (daily equivalent dexamethasone 10 mg; hazard ratio (95% CI) = 0.56 (0.38-0.84), P = 0.005] without increasing the risk of infection. Modification of steroid dosing strategy as well as steroid type may further optimize therapeutic effect of the COVID-19 treatment
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