Tocilizumab in Severe COVID-19 Disease: Does Timing Matters?

Abstract

Rationale: The COVID-19 pandemic has affected nearly every country, becoming a global health problem with social and economic consequences for years to come. To date, there are several agents under active investigation as potential treatments, among them is the interleukin-6 receptor blocker tocilizumab. Early observational studies have identified an association between the use of tocilizumab and a decreased risk of intubation and/or death, however randomized clinical trials have not found a significant benefit yet. The aim of our study was to assess whether the timing of tocilizumab influenced the outcome of patients with severe COVID-19. Methods: This is a retrospective observational study involving 56 Ecuadorian patients treated with corticosteroids plus tocilizumab after a confirmed diagnosis of severe COVID-19 respiratory disease in the context of a hyperinflammatory state. A hyperinflammatory state was defined by the SIRS criteria plus at least 1 of the following three: i.) CRP >100 mg/L, ii.) serum ferritin >900 μg/L on one occasion or a twofold increase of the level at admission within 48 hours;or iii.) D-dimer level >1500 μg/L. Descriptive statistics were reported. A point-biserial correlation was conducted to assess the relationship between symptomatic days prior treatment with survival status. Furthermore, a chi-square test for association was performed between corticosteroids/tocilizumab dosage and survival status. All the data was analyzed using SPSS, version 24.0 software (SPSS Inc., Chicago, IL, USA). For all test a p-value of less than 0.05 will be considered statistically significant. Results: The sample mean age was 61.7 (SD 10.9) years with a 7:3 male/female ratio. 76.8% (n=43) patients survived with a mean time to hospital discharge of 11.5 days (SD 12.0). Regarding treatment, average days prior to corticosteroids administration was 2.6 (SD 2.5), while 11.1 (SD 9.0) was for tocilizumab. A statistically significant negative correlation between days prior tocilizumab administration and survival status was reported (rpb =-.290, n = 56, p = .030) (Figure 1). On the other hand, no significant association between tocilizumab dosage and survival status was determined (χ2 (5) = 3.566, p = .600). Same analyses with corticosteroids yielded non-significant results. Conclusion: Early administration of tocilizumab was associated with a greater likelihood of surviving, an observation that could not be reproduced with corticosteroids. The association between tocilizumab dosage and survival status, however, was not statistically significant. Further large-scale studies are needed to confirm the exact role of the timing of tocilizumab in patients with severe COVID-19. (Table Presented).