Abstract
Background Severe COVID-19 is characterised by interstitial pneumonia and hyperinflammation, with elevated levels of pro-inflammatory cytokines, such as IL-6. Effective treatments are urgently needed, and IL-6 is a rational target to reduce hyperinflammation.
Methods An observational, control cohort, single-centre study initiated at the Papa Giovanni XXIII Hospital in Bergamo, Italy included patients with COVID-19 confirmed by a nasopharyngeal swab positive for severe acute respiratory syndrome coronavirus 2 RNA and interstitial pneumonia requiring ventilatory support. Patients were treated with either best supportive care and siltuximab or best supportive care alone. Propensity score matching was applied to minimise differences in baseline covariates between patient cohorts. The main outcome was mortality in siltuximab-treated patients compared with patients in the matched-control cohort. This study (Siltuximab in Severe COVID-19, SISCO) is registered with ClinicalTrials.gov, identifier NCT04322188.
Findings Thirty patients received siltuximab, while 188 control patients received only best supportive care. Siltuximab-treated patients were matched to 30 control patients using the propensity score analysis of baseline covariates. The 30-day mortality rate was significantly lower in the siltuximab-treated than the matched-control cohort patients (HR 0·462, 95% CI 0·221– 0·965); p=0·0399). The mean follow-up was 33·3 days (range 7–58 days) for the siltuximab-treated patients and 22·8 days (range 2–45 days) for the control cohort. Sixteen siltuximab-treated patients were discharged from hospital, four remained on mechanical ventilation, and 10 patients died.
Interpretation Patients with rapidly progressing COVID-19 respiratory failure requiring ventilatory support may benefit from treatment with siltuximab to reduce mortality and cytokine-driven hyperinflammation associated with severe disease. These findings require validation in a randomised controlled clinical trial.
Funding Papa Giovanni XXIII Hospital and the Italian Association for Cancer Research funded the study. EUSA Pharma supplied siltuximab, and provided funding for data collection, analysis, and development of the publication.
Competing Interest Statement
Declaration of interests Jonathan P Morgan, Benjamin MJ Owens and Karan JK Kanhai are employees of EUSA Pharma. Alessandro Rambaldi reports consultancy fees from Amgen, Novartis, Pfizer, Celgene, Italfarmaco, Gilead, Roche and Omeros, travel support from Amgen, Novartis, Celgene, Italfarmaco, Gilead and Roche, and research grants from Amgen, Italfarmaco and Roche, outside the submitted work. Caterina Mico reports travel support from Medac, outside the submitted work. Diego Ripamonti reports personal fees from Gilead, Janssen and ViiV, outside the submitted work. Fabiano Di Marco reports grants from Boehringer Ingelheim, GSK, Novartis and AZ, and personal fees from Boehringer Ingelheim, GSK, Chiesi, Zambon, Novartis, Guidotti/Malesci, AZ, Menarini, Mundipharma, TEVA and Almiral, outside the submitted work. Guiseppe Gritti reports non-financial support from Gilead Kite, Roche, Takeda and Janssen, and personal fees from Gilead Kite, Autolus, Roche, IQvia, Takeda, Amgen and Italfarmaco, outside the submitted work. Ivano Riva reports travel support from Aferetica outside the submitted work. Stefano Fagiuoli reports grants from Gilead and Novartis and personal fees from Gilead, Abbvie, MSD, Novartis, Bayer, Astellas, Kedrion, and Intercept, outside the submitted work. All other authors declare no competing interests.
Clinical Trial
NCT04322188
Funding Statement
Papa Giovanni XXIII Hospital and the Italian Association for Cancer Research funded the study. EUSA Pharma supplied siltuximab, and provided funding for data collection, analysis, and development of the publication.
Author Declarations
All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.
Yes
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
Yes
I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
Data Availability
All data will be made available upon reasonable requests submitted to the authors.
