Efficacy of tocilizumab for hospitalized patients with COVID-19 pneumonia and high IL-6 levels: A randomized controlled trial

Abstract

Acute respiratory distress syndrome; COVID-19; Interleukin-6

Síndrome de dificultat respiratòria aguda; COVID-19; Interleucina-6

Síndrome de dificultad respiratoria aguda; COVID-19; Interleucina-6

Background The objective of this clinical trial is to evaluate the efficacy and safety of IL-6 driven personalized treatment strategy with tocilizumab in patients with severe COVID-19 pneumonia. Trial design Randomized, controlled, open-label, single-center trial of a tocilizumab treatment strategy in adult patients hospitalized with severe COVID-19 pneumonia and IL-6 serum levels > 40 pg/mL. Methods Patients were randomized 1:1 to receive standard of care (SOC) or SOC plus one dose of tocilizumab. The primary outcome was death or need for invasive mechanical ventilation (IMV) within 28 days after randomization. Secondary outcomes included ICU admission, days on IMV and hospital stay. A meta-analysis of clinical trials to evaluate the effect of tocilizumab on mortality and need of IMV in patients with COVID-19 pneumonia was performed. Results Sixty-two patients were included: 30 in the SOC arm and 32 in the standard-treatment plus tocilizumab arm. The primary outcome occurred in 12.9% in the tocilizumab arm and 32.3% in the SOC arm(p = 0.068). There was a trend towards fewer days on IMV (7.5 vs 19.5 days, p = 0.073) and a shorter hospital stay (4 vs 8 days, p = 0.134) in the tocilizumab group. No serious adverse events were reported. The meta-analysis revealed a RR for death or IMV of 0.83 (95% CI: 0.77–0.89) in patients receiving tocilizumab, compared to patients receiving SOC. Conclusion Tocilizumab could be effective to prevent death or IMV in patients with severe COVID-19 pneumonia and high IL-6 serum levels. Safety profile of tocilizumab does not arise major concern in patients with severe COVID19.

Open Access Funding provided by Universitat Autonoma de Barcelona. This study received support of “Plataforma ISCIII de Soporte para la Investigación Clínica—SCReN (Spanish Clinical Research Network)” which is funded by ISCIII through the project sPT17/0017/0030 and PT20/00078, which are both integrated in the “Plan Estatal de I + D + I 2013–2016 y 2017–2020” and co-funded by the “ Fondo Europeo de Desarrollo Regional (FEDER) “Una manera de hacer Europa””. ASM was supported by the Instituto de Salud Carlos III (Juan Rodés postdoctoral fellowship grant number JR18/00022) during the study period. JSN and JEP are supported by the Instituto de Salud Carlos III (Rio Hortega predoctoral grant numbers CM22/00262 and CM22/00246).