Survival and outcomes of tocilizumab use in severe and critically ill COVID-19 patients not responding to steroids Background

ABSTRACT

Background: Mortality and morbidity are highest in severe and critically ill patients with COVID -19 pneumonia. Recently corticosteroids have shown a definite mortality benefit in these patients. In this study we used interleukin-6 inhibitor, tocilizumab in patients who failed to show any clinical improvement after initial treatment with steroids. Patients and Methods: This is a retrospective observational study in Severe and critical COVID 19 patients, who got admitted to intensive care unit and subsequently received tocilizumab were included. Patients who worsened clinically or had no change in oxygen requirement even after 24hrs of receiving Intravenous methylprednisolone at a dose of 1-2mg/kg/day had received tocilizumab (maximum total dose of 800mg) intravenously. All-cause mortality and progression to mechanical ventilation at day 28 were the primary outcome measures. Clinical improvement and oxygen requirements after tocilizumab administration along with trends in inflammatory markers were secondary outcome. Secondary infections rates and other drug related side effects were also noted. Results: A total of 51 patients who did not show clinical improvement even after 24 hours of intravenous steroids and received tocilizumab were included. In these patients, there was a significant decrease in oxygen requirement by day 3 and clinical improvement by day 7 of tocilizumab administration. Among the inflammatory markers, we observed elevated median baseline values of CRP (114.2 mg/L) , IL-6 (55.4 pg/ml) and Neutrophil to Lymphocyte Ratio (12.4). Out of these only CRP showed a significant decrease after the drug administration. 13 (26.5%) of the 49 patients who were on non-invasive or conventional oxygen support progressed to mechanical ventilation. The day 28 all-cause mortality rate was 10/51(19.6%). 10(19.6%) of the 51 patients had life threatening infections, 1 patient had colonic perforation and 1 patient had transaminitis following tocilizumab administration. Conclusion: Early and timely administration of tocilizumab is a viable option in selected severe and critical covid 19 patients who do not respond to initial steroids. When given along with steroids?, incidence of life threatening infections seems to increase, hence a high suspicion of secondary infection should be kept.