Tocilizumab in patients with severe COVID-19: a retrospective cohort study
Open accessAbstract
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.
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- Authors
- Guaraldi, G., Meschiari, M., Cozzi-Lepri, A., Milic, J., Tonelli, R., Menozzi, M., Franceschini, E., Cuomo, G., Orlando, G., Borghi, V., Santoro, A., Di Gaetano, M., Puzzolante, C., Carli, F., Bedini, A., Corradi, L., Fantini, R., Castaniere, I., Tabbì, L., Girardis, M., Tedeschi, S., Giannella, M., Bartoletti, M., Pascale, R., Dolci, G., Brugioni, L., Pietrangelo, A., Cossarizza, A., Pea, F., Clini, E., Salvarani, C., Massari, M., Viale, P. L., & Mussini, C.
- Affiliations
- University of Modena and Reggio Emilia (IT)
- Azienda Ospedaliero-Universitaria di Modena (IT)
- University of Bologna (IT)
- University of Udine (IT)
- Azienda Sanitaria Unità Locale di Reggio Emilia (IT)
- Corresponding author
- Mussini, Cristina
- ORCID
- Guaraldi, Giovanni
- Meschiari, Marianna
- Tonelli, Roberto
- Menozzi, Marianna
- Franceschini, Erica
- Cuomo, Gianluca
- Orlando, Gabriella
- Santoro, Antonella
- Puzzolante, Cinzia
- Carli, Federica
- Bedini, Andrea
- Fantini, Riccardo
- Castaniere, Ivana
- Tabbì, Luca
- Girardis, Massimo
- Tedeschi, Sara
- Giannella, Maddalena
- Bartoletti, Michele
- Pascale, Renato
- Dolci, Giovanni
- Brugioni, Lucio
- Pietrangelo, Antonello
- Cossarizza, Andrea
- Pea, Federico
- Clini, Enrico
- Salvarani, Carlo
- Massari, Marco
- Mussini, Cristina
- Venue
- The Lancet Rheumatology
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 2
- Issue
- 8
- Pages
- e474-e484
- ISSN
- 2665-9913 (ISSN-L)
- PMC
- PMC7314456
- OpenAlex
- W3036398841
- Cited by
- 939
- References
- 36
- Citations by year
- 2026: 5 · 2025: 22 · 2024: 34 · 2023: 69 · 2022: 138 · 2021: 381 · 2020: 290
- FWCI
- 28.80
- Type
- journal article
- Language
- en
- Update notices
- erratum (2020-10-01)
- Open access
- bronze
- doi.org
- Locations
- The Lancet Rheumatology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System (University of Udine) (submittedVersion, cc-by-nc-nd)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by-nc-nd)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- FP7 Information and Communication Technologies
- Topics
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- tocilizumab, severe COVID-19 pneumonia, IL-6 receptor inhibition, invasive mechanical ventilation, mortality, subcutaneous tocilizumab, intravenous tocilizumab, standard of care treatment, SOFA score, cytokine storm, hydroxychloroquine, azithromycin, low molecular weight heparin
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