Comparative study of monoclonal anti-IL6 antibodies in severe new coronavirus disease COVID-19 patients. Retrospective cohort study

Abstract

Introduction. Novel coronavirus infection (COVID-19) is characterized by systemic hyper-inflammation with elevated inflammatory cytokines, that has been recognized as a leading cause of severity COVID-19. Many clinical evidences have indicated the importance of anti-inflammatory immunomodulation therapy in severe COVID-19, especially anti-IL6 monoclonal antibodies. Objectives. Comparative study of the monoclonal anti-IL6 antibodies in severe COVID-19 patients. Materials and methods. Single-center observational retrospective cohort study included three groups of hospitalized COVID-19 patients treated with one-dose tocilizumab (Group 1, 200 patients), levilimab (Group 2, 100 patients), and olokizumab (Group 3, 100 patients). Main parameters at baseline included: C-reactive protein serum concentration, and lung CT score. End-points included: sepsis and in-hospital death. Results. No significant difference in demographic characteristics and main parameters at baseline were found. A comparative analysis of clinical outcomes in the group revealed a statistically significant increase in the risk of sepsis and death in the levilimab group compared with the tocilizumab and olokizumab groups. When comparing the “Lethal outcome” indicator depending on the drug, we were unable to identify significant differences (p = 0.259, Fisher's exact test for multi-field tables), as in the “Sepsis” outcome (p = 0.587, Fisher's exact test for multi-field tables) When comparing tocilizumab for s/c and i.v. administration, we were unable to identify statistically significant differences (p = 0.293, Exact test Fisher) The odds of sepsis in the subcutaneous group were 2.28 times lower than in the intravenous group; the odds differences were not statistically significant (OR = 0.44, 95% CI 0.1–1.88). Conclusions. The use in patients with severe COVID-19 of different drugs of monoclonal antibodies against interleukin 6 did not reveal significant differences in deaths between tocilizumab, levilimab and olokizumab. The identified differences between the drugs in the incidence of sepsis and death require further randomized controlled trials.