Tocilizumab in patients with severe COVID-19: a retrospective cohort study
Prof Giovanni Guaraldi, MD Marianna Meschiari, Alessandro Cozzi-Lepri, MD Jovana Milic, Roberto Tonelli, MD Marianna Menozzi, Erica Franceschini, MD Gianluca Cuomo, PhD Gabriella Orlando, MD Vanni Borghi, MD Antonella Santoro, Margherita Di Gaetano, PhD Cinzia Puzzolante, MD, A Bedini MD Federica Carli, Andrea Bedini, MD Luca Corradi, MD Riccardo Fantini, Ivana Castaniere, PhD, I Castaniere MD Luca Tabbì, Prof Massimo Girardis, MD Sara Tedeschi, Prof Maddalena Giannella, PhD Michele Bartoletti, MD Renato Pascale, MD Giovanni Dolci, Lucio Brugioni, Antonello Pietrangelo, Prof Andrea Cossarizza, Federico Pea, Prof Enrico Clini, MD Carlo Salvarani, Marco Massari, Prof Pier Luigi Viale, Prof Cristina Mussini
The Lancet Rheumatology, doi:10.1016/s2665-9913(20)30173-9
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.
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