Safety and efficacy of anti-il6-receptor tocilizumab use in severe and critical patients affected by coronavirus disease 2019: A comparative analysis

Abstract

Background: As the novel SARS-CoV-2 pandemic occurred, no specific treatment was yet available. Inflammatory response secondary to viral infection might be the driver of severe diseases. We report the safety and efficacy (in terms of overall survival and hospital discharge) of the anti-IL6 tocilizumab (TCZ) in subjects with COVID-19. Methods: This retrospective, single-center analysis included all the patients consecutively admitted to our Hospital with severe or critical COVID-19 who started TCZ treatment from March 13th to April 03rd, 2020. A 1:2 matching to patients not treated with TCZ was performed according to age, sex, severity of disease, P/F, Charlson Comorbidity Index and length of time between symptoms onset and hospital admittance. Descriptive statistics and non-parametric tests to compare the groups were applied. Kaplan Meier probability curves and Cox regression models for survival, hospital discharge and orotracheal intubation were used. Results: Seventy-four patients treated with TCZ were matched with 148 matched controls. They were mainly males (81.5%), Caucasian (82.0%) and with a median age of 59 years. The majority (69.8%) showed critical stage COVID-19 disease. TCZ use was associated with a better overall survival (HR 0.499 [95% CI 0.262-0.952], p = 0.035) compared to controls but with a longer hospital stay (HR 1.658 [95% CI 1.088-2.524], p = 0.019) mainly due to biochemical, respiratory and infectious adverse events. Discussion: TCZ use resulted potentially effective on COVID-19 in terms of overall survival. Caution is warranted given the potential occurrence of adverse events. Financial support: Some of the tocilizumab doses used in the subjects included in this analysis were provided by the "Multicenter study on the efficacy and tolerability of tocilizumab in the treatment of patients with COVID-19 pneumonia" (EudraCT Number: 2020-001110-38) supported by the Italian National Agency for Drugs (AIFA). No specific funding support was planned for study design, data collection and analysis and manuscript writing of this paper.

Tocilizumab improves survival in severe COVID-19 pneumonia with persistent hypoxia: A retrospective cohort study with follow-up from Mumbai, India

“…to 48 of admission. Rossotti et al 16 reported tocilizumab use to be associated with a better overall survival (HR 0.499 [ 95% CI 0.262-0.952], p = 0.035) as compared to control, their inclusion criteria being respiratory rate more than or equal to 30 per min, Oxygen saturation less than or equal to 93% on room air or PaO2/FiO2 ratio being 300 or less.…”

Tocilizumab improves survival in severe COVID-19 pneumonia with persistent hypoxia: A retrospective cohort study with follow-up from Mumbai, India

“…Guaraldi et al 7 reported mortality in tocilizumab versus standard care group to be 7% and 20% respectively (P<.0001), with inclusion criteria being respiratory rate more than or equal to 30 per min, Oxygen saturation less than or equal to 93% on room air or PaO2/FiO2 ratio being 300 or less, and bilateral lung in ltrates more than 50% being present within 24 to 48 of admission. Rossotti et al 16 reported tocilizumab use to be associated with a better overall survival (HR 0.499 [ 95% CI 0.262-0.952], p=0.035) as compared to control, their inclusion criteria being respiratory rate more than or equal to 30 per min, Oxygen saturation less than or equal to 93% on room air or PaO2/FiO2 ratio being 300 or less.…”

A “Window of Therapeutic Opportunity” for Anti-Cytokine Therapy in Patients With Coronavirus Disease 2019

“…Furthermore, iatrogenic immunosuppression could promote bacterial, fungus, or viral infectious complications, as shown with the targeting of IL-6 with tocilizumab in observational studies on patients not requiring mechanical ventilation ( 18 , 55 ). Also at later stages, pharmacologically induced immunosuppression in already immunocompromised patients could adversely affect the course of the disease, as suggested by the finding of significantly longer periods of hospitalization and higher rates of mortality in ventilated patients treated with tocilizumab ( 15 , 16 ) or high-doses corticosteroids ( 56 , 57 ).…”