Objectives To assess the safety and efficacy of interleukin (IL)−6 blockade with sarilumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation.
Methods We conducted an open-label study of sarilumab in severe COVID-19 pneumonia (PaO2/FiO2 <300 mm Hg) with hyperinflammation (elevated inflammatory markers and serum IL-6 levels). Sarilumab 400 mg was administered intravenously in addition to standard of care and results were compared with contemporary matched patients treated with standard of care alone. Clinical improvement, mortality, safety and predictors of response were assessed at 28 days.
Results Twenty-eight patients were treated with sarilumab and 28 contemporary patients receiving standard of care alone were used as controls. At day 28 of follow-up, 61% of patients treated with sarilumab experienced clinical improvement and 7% died. These findings were not significantly different from the comparison group (clinical improvement 64%, mortality 18%; p=NS). Baseline PaO2/FiO2 ratio >100 mm Hg and lung consolidation <17% at CT scan predicted clinical improvement in patients treated with sarilumab. Median time to clinical improvement in patients with lung consolidation <17% was shorter after sarilumab (10 days) than after standard treatment (24 days; p=0.01). The rate of infection and pulmonary thrombosis was similar between the two groups.
Conclusions At day 28, overall clinical improvement and mortality in patients with severe COVID-19 were not significantly different between sarilumab and standard of care. Sarilumab was associated with faster recovery in a subset of patients showing minor lung consolidation at baseline.
- anti-inflammatory agents, non-steroidal
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Handling editor Josef S Smolen
Collaborators SARI-RAF Study Group members: Piera Angelillo; Andrea Assanelli; Elena Baldissera; Nicola Boffini; Enrica Paola Bozzolo; Stefania Calvisi; Corrado Campochiaro; Valentina Da Prat; Diana Canetti; Adriana Cariddi; Antonella Castagna; Giulio Cavalli; Maria Pia Cicalese; Fabio Ciceri; Lorenzo Dagna; Francesco De Cobelli; Giacomo De Luca; Emanuel Della-Torre; Giuseppe Di Lucca; Gaetano di Terlizzi; Nicola Farina; Maria Fazio; Salvatore La Marca; Giovanni Landoni; Marco Lanzillotta; Gaia Mancuso; Giacomo Monti; Luca Moroni; Angela Napolitano; Chiara Oltolini; Diego Palumbo; Marco Ripa; Patrizia Rovere-Querini; Annalisa Ruggeri; Silvia Sartorelli; Paolo Scarpellini; Marzia Spessot; Alessandro Tomelleri; Moreno Tresoldi; Alberto Zangrillo.
Contributors Substantial contributions to the conception or design of the work, or the acquisition, analysis or interpretation of data: all authors. Drafting the work or revising it critically for important intellectual content: ED-T and LD drafted the work. All authors revised the manuscript and gave important intellectual contribution. Final approval of the version published: all author approved the final version of the manuscript. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding This study was supported by institutional funding.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Ethics approval This study was approved by the San Raffaele Hospital Ethical Committee (no. 34/int/2020).
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.