Tocilizumab Plus Dexamethasone in Patients with Moderate-to-Severe COVID-19 Pneumonia: a Randomized Clinical Trial of the CORIMUNO-19 Study Group

Background: In moderate-to-severe COVID-19 pneumonia, dexamethasone (DEX) and tocilizumab (TCZ) reduce the occurrence of death and ventilatory support. The efficacy and safety of combining the two drugs remains to be investigated.Methods: Patients with moderate-to-severe COVID-19 pneumonia (WHO class 5) requiring oxygen (>3 L/min) were randomly assigned to receive DEX (10mg/d 5 days tapering up to 10 days) alone or combined with TCZ (8mg/kg IV) at day 1 possibly repeated with a fixed dose of 400 mg i.v at day 3. The primary outcome was time from randomization to mechanical ventilation support or death up to day 14, analyzed on an intent-to-treat basis using a Bayesian approach.Findings: A total of 453 patients were randomized, 3 withdrew consent, 450 were analyzed of whom 226 and 224 patients were assigned to receive DEX or TCZ+DEX, respectively. At day 14, mechanical ventilation or death occurred in 32/226 (14%) and 27/224 (12%) in the DEX and TCZ+DEX arms, respectively (Hazard ratio (HR) [90% credible interval (CrI)], 0.85 [0.55-1.31]). At day 14, WHO CPS scale was significantly improved in the TCZ+DEX arm (OR 0.69, (95% CrI, 0.49 to 0.97). On day 90, 24 deaths (11%) were observed in the DEX arm and 18 (8%) in the TCZ+DEX arm (HR 0.77, 95% CI 0.42-1.41). Patients with at least one serious adverse event were observed in 25 and 21% in DEX and TCZ+DEX arms, respectively.Interpretation: Mechanical ventilation need and mortality were not improved with combination of TCZ and DEX compared with DEX alone. The safety of both treatments was similar. However, given the wide confidence intervals for the estimate of effect, the findings do not allow for a definitive interpretation.Trial Registration: ClinicalTrials.gov number, NCT04476979.Funding: Funded by PHRCDeclaration of Interest: None to declare. Ethical Approval: The CORIMUNO Cohort and all embedded trials (i.e. trials using data collected in the CORIMUNO cohort) were approved by an ethics committee (CPP Île-de-France VI) and relevant authorities.