Repurposed Tocilizumab in Patients with Severe COVID-19

Abstract

The coronavirus disease 2019 (COVID-19) has caused a global pandemic, resulting in considerable morbidity and mortality. Tocilizumab, an inhibitor of IL-6, has been widely repurposed as a treatment of severely ill patients without robust evidence supporting its use. In this study, we aimed to systematically describe the effectiveness of treatment and prevention of the cytokine storms in COVID-19 patients with tocilizumab. In this multicentered retrospective and observational cohort study, 65 patients with COVID-19 receiving tocilizumab and 130 not receiving tocilizumab were propensity score matched at a ratio of 2:1 based on age, sex, and comorbidities from January 20, 2020 to March 18, 2020 in Wuhan, China. After adjusting for confounding, the detected risk for in-hospital death was lower in the tocilizumab group versus nontocilizumab group (hazard ratio = 0.47; 95% confidence interval = 0.25–0.90; p = 0.023). Moreover, use of tocilizumab was associated with a lower risk of acute respiratory distress syndrome (odds ratio = 0.23; 95% confidence interval = 0.11–0.45; p < 0.0001). Furthermore, patients had heightened inflammation and more dysregulated immune cells before treatment, which might aggravate disease progression. After tocilizumab administration, abnormally elevated IL-6, C-reactive protein, fibrinogen, and activated partial thromboplastin time decreased. Tocilizumab may be of value in prolonging survival in patients with severe COVID-19, which provided a novel strategy for COVID-19–induced cytokine release syndrome. Our findings could inform bedside decisions until data from randomized, controlled clinical trials become available.

Efficacy and secondary infection risk of tocilizumab, sarilumab and anakinra in COVID‐19 patients: A systematic review and meta‐analysis

“…Thirdly, every doctor has a different treatment for clinical diagnostic and treatment algorithms, which would allow for adjustment by other factors. 3 , 25 , 26 , 27 In addition, the inclusion of zero‐event trials can sometimes decrease the effect size estimate and narrow the CIs.…”

Intensive Care Patients from the First COVID-19 Wave: One-Year Survival after Tocilizumab Treatment

“…The meta-analysis by Wei et al describes a possible positive effect of tocilizumab, especially for critical patients, and follow-up data of the largest and blinded clinical trials are still being conducted [40]. According to Stone et al, it is not possible to exclude that the treatments decreased the harmful inflammatory syndrome, but there is no evidence of a positive effect: further follow-up trials could clarify the value of this potential effect [41,42].…”

Complement C5a and Clinical Markers as Predictors of COVID-19 Disease Severity and Mortality in a Multi-Ethnic Population

“…Hence, tocilizumab and sarilumab were proposed as promising therapeutic strategies to reduce mortality in COVID-19, by blocking IL-6 signalling, and ameliorating the deleterious effects of the inflammatory storm ( 20 ). The RECOVERY trial study recently demonstrated the effectiveness of tocilizumab and dexamethasone combined in improving the survival rate and reducing the risk for ventilatory assistance in COVID-19 patients ( 21 ).…”

“…The RECOVERY trial study recently demonstrated the effectiveness of tocilizumab and dexamethasone combined in improving the survival rate and reducing the risk for ventilatory assistance in COVID-19 patients (21).…”