Tocilizumab Improves the Prognosis of COVID-19 in Patients with High IL-6

Abstract

Background: Despite direct viral effect, 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. Significant effect of TCZ on death was demonstrated in patients with 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 administration in COVID-19 reduces mortality and speed up clinical improvement in patients with a baseline concentration of IL-6>100 pg/ml, particularly if they need oxygen supplementation due to SpO2 ≤90%.Funding Statement: The study was supported by the Polish Association of Epidemiologists and Infectiologists and Medical Research Agency.Declaration of Interests: RF reports grants from Abbvie, Gilead, Merck, personal fees from Gilead, Abbvie, Merck, Roche, and non-financial support from Abbvie, Gilead, and Merck outside the submitted work. DZM, PP reports personal fees from Gilead and Abbvie, outside the submitted work. JJ reports personal fees from Gilead, Abbvie, Bausch Health, Merck, Promed, Roche, and non-financial support from Abbvie, Gilead, and Merck outside the submitted work. KS reports personal fees from Gilead, Abbvie, Merck, outside the submitted work KT reports personal fees from Gilead, Abbvie, Merck, Promed, Roche, and non-financial support from Abbvie, Gilead, and Merck outside the submitted work. JK reports personal fees from Gilead, Merck, ViiV, Janssen outside the submitted work. IML reports personal fees from Gilead, Abbvie and Pfizer ABK, JP, BB, KK, MP, AP, DK, MTZ, CI, MRog, MRor declare no competing interests.Ethics Approval Statement: The study received the approval of the Ethics Committee of the Medical University of Białystok.