Administration of tocilizumab to patients with high concentrations of IL-6 in the course of COVID-19 is associated with a better prognosis

Flisiak, R.; Jaroszewicz, J.; Rogalska, M.; Lapinski, T.; Berkan-Kawinska, A.; Bolewska, B.; Tudrujek-Zdunek, M.; Kozielewicz, D.; Rorat, M.; Leszczynski, P.; Klos, K.; Kowalska, J.; Pabjan, P.; Piekarska, A.; Mozer-Lisewska, I.; Tomasiewicz, K.; Pawlowska, M.; Simon, K.; Polanska, J.; Zarebska-Michaluk, D.

Background Despite the direct viral activity, the pathogenesis of coronavirus disease 2019 (COVID-19) includes an overproduction of cytokines including interleukin 6 (IL-6). Therefore tocilizumab (TCZ), a monoclonal antibody against IL-6 receptors, became considered as a possible therapeutic option. Methods Patients were selected from the SARSTer national database, which included 2332 individuals with COVID-19 and the current study included 825 adult patients with moderate to severe course. The retrospective analysis was performed in 170 patients treated with TCZ and 655 without this medication or any other anti-cytokine therapy. The end-points of treatment effectiveness were a rate of death, need for mechanical ventilation, and clinical improvement. Results Patients treated with TCZ were balanced compared to non-TCZ regarding gender, age, BMI, and prevalence of coexisting conditions. The reduced death rate was demonstrated in patients treated with TCZ and baseline IL-6 >100 pg/ml (hazard ratio [HR]: 0.27, 95% confidence interval [CI]:0.10-0.78), or those needing oxygen supplementations who worsened within 7 days of hospitalization (HR: 0.38, 95% CI:0.16-0.88). The best effectiveness of TCZ was achieved in patients with a combination of baseline IL-6>100 pg/ml and either SpO2[≤]90% (HR for death, mechanical ventilation, and clinical improvement after 21 or 28 days: 0.07, 0.14, 5.53, 5.18 respectively) or requiring oxygen supplementation (HR for death and clinical improvement after 21 or 28 days, 0.18, 2.66, 2.85 respectively). Conclusions Tocilizumab administered for COVID-19 in patients with a baseline concentration of IL-6>100 pg/ml is associated with reduced mortality and faster clinical improvement, particularly if there is a need for oxygen supplementation due to SpO2[≤]90%.