Inflammatory parameter analysis in severe COVID-19 patients treated with tocilizumab

ABSTRACT

Background and importance Tocilizumab (TCZ) is an immunosuppressor drug, IL-6 inhibitor, indicated for the treatment of rheumatoid arthritis and cytokine release syndrome associated with CAR T cell therapy. It was proposed as a compassionate treatment for severe COVID-19 due to its potential benefit as anticytokine therapy with IL-6 as the target, one of the most relevant cytokines involved in the cytokine storm induced by COVID-19. Aim and objectives The main objective was to evaluate TCZ effectiveness in the modification of inflammatory parameters in severe COVID-19 patients. Material and methods A retrospective observational study was conducted in 46 patients with COVID-19 admitted to an intensive care unit (ICU) and treated with TCZ from 20 March to 20 May 2020 at a tertiary hospital. Variables analysed were age, sex, levels of IL-6, C reactive protein (CRP), ferritin, lymphocytes count and D-dimer on days 0, 1, 3, 7 and 14 after TCZ administration. Days in the ICU, deaths and patient outcomes were also obtained. Results Median age was 64 years and 67.4% of patients were men. IL-6 levels on day 0 were 293 pg/mL, peaking at 416 pg/mL on day 3 and decreasing to 241.9 pg/mL on day 7. CRP levels increased above the normal range (median 53.35 mg/L on day 0) in all patients before initiation of therapy with TCZ and decreased on day 7 (median 3 mg/L). Serum ferritin decreased from 1798 mg/L on day 1 to 1197.5 mg/L on day 7 before TCZ. Lymphocyte count increased from 570 to 1365 lymphocytes/mL on day 7. D-dimer level on day 0 was 2008 ng/mL and increased to 3910 ng/mL on day 7 and decreased to 1723 ng/mL on day 14. Length in ICU stay was 16.4 days compared with the mean stay of the total number of ICU COVID patients, which was 26.1 days. Mortality was 19.6%, 15.2% remained in hospital at the end of the study and 65.2% were discharged. Conclusion and relevance The results showed an improvement in inflammatory markers with TCZ treatment, as well as a decrease in length of stay in the ICU, similar to findings reported in the literature. Nevertheless, because of potential bias due to patients receiving different treatments before and after TCZ and the small sample size, it is necessary to confirm these results in controlled clinical studies.