Tocilizumab in patients with severe COVID-19: a retrospective cohort study

Giovanni Guaraldi, Marianna Meschiari, Alessandro Cozzi-Lepri, Jovana Milic, Roberto Tonelli, Marianna Menozzi, Erica Franceschini, Gianluca Cuomo, Gabriella Orlando, Vanni Borghi, Antonella Santoro, Margherita Di Gaetano, Cinzia Puzzolante, Federica Carli, Andrea Bedini, Luca Corradi, Riccardo Fantini, Ivana Castaniere, Luca Tabbì, Massimo GirardisSara Tedeschi, Maddalena Giannella, Michele Bartoletti, Renato Pascale, Giovanni Dolci, Lucio Brugioni, Antonello Pietrangelo, Andrea Cossarizza, Federico Pea, Enrico Clini, Carlo Salvarani, Marco Massari, Pier Luigi Viale, Cristina Mussini

Research output: Contribution to journalArticlepeer-review

Abstract

Background: No therapy is approved for COVID-19 pneumonia. The aim of this study was to assess the role of tocilizumab in reducing the risk of invasive mechanical ventilation and death in patients with severe COVID-19 pneumonia who received standard of care treatment.

Methods: This retrospective, observational cohort study included adults (≥18 years) with severe COVID-19 pneumonia who were admitted to tertiary care centres in Bologna and Reggio Emilia, Italy, between Feb 21 and March 24, 2020, and a tertiary care centre in Modena, Italy, between Feb 21 and April 30, 2020. All patients were treated with the standard of care (ie, supplemental oxygen, hydroxychloroquine, azithromycin, antiretrovirals, and low molecular weight heparin), and a non-randomly selected subset of patients also received tocilizumab. Tocilizumab was given either intravenously at 8 mg/kg bodyweight (up to a maximum of 800 mg) in two infusions, 12 h apart, or subcutaneously at 162 mg administered in two simultaneous doses, one in each thigh (ie, 324 mg in total), when the intravenous formulation was unavailable. The primary endpoint was a composite of invasive mechanical ventilation or death. Treatment groups were compared using Kaplan-Meier curves and Cox regression analysis after adjusting for sex, age, recruiting centre, duration of symptoms, and baseline Sequential Organ Failure Assessment (SOFA) score.

Findings: Of 1351 patients admitted, 544 (40%) had severe COVID-19 pneumonia and were included in the study. 57 (16%) of 365 patients in the standard care group needed mechanical ventilation, compared with 33 (18%) of 179 patients treated with tocilizumab (p=0·41; 16 [18%] of 88 patients treated intravenously and 17 [19%] of 91 patients treated subcutaneously). 73 (20%) patients in the standard care group died, compared with 13 (7%; p<0·0001) patients treated with tocilizumab (six [7%] treated intravenously and seven [8%] treated subcutaneously). After adjustment for sex, age, recruiting centre, duration of symptoms, and SOFA score, tocilizumab treatment was associated with a reduced risk of invasive mechanical ventilation or death (adjusted hazard ratio 0·61, 95% CI 0·40-0·92; p=0·020). 24 (13%) of 179 patients treated with tocilizumab were diagnosed with new infections, versus 14 (4%) of 365 patients treated with standard of care alone (p<0·0001).

Interpretation: Treatment with tocilizumab, whether administered intravenously or subcutaneously, might reduce the risk of invasive mechanical ventilation or death in patients with severe COVID-19 pneumonia.

Funding: None.

Original languageEnglish
Pages (from-to)e474-e484
JournalThe Lancet Rheumatology
Volume2
Issue number8
DOIs
Publication statusPublished - Aug 2020

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