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All Studies   All Outcomes    Recent:   

Siltuximab downregulates interleukin-8 and pentraxin 3 to improve ventilatory status and survival in severe COVID-19

Gritti et al., Leukemia, doi:10.1038/s41375-021-01299-x
May 2021  
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Prospective observational study of 30 hospitalized COVID-19 patients requiring ventilatory support in Italy, showing improved ventilatory status and survival with siltuximab treatment, particularly with the reduction of IL-8 and PTX3 levels 4 days after treatment. There was no control group.
Gritti et al., 24 May 2021, retrospective, Italy, peer-reviewed, 22 authors. Contact: g.gritti@asst-pg23.it.
This PaperSiltuximabAll
Abstract: Leukemia (2021) 35:2710–2714 https://doi.org/10.1038/s41375-021-01299-x LETTER INFECTIOUS MEDICINE, VIROLOGY Siltuximab downregulates interleukin-8 and pentraxin 3 to improve ventilatory status and survival in severe COVID-19 Giuseppe Gritti 1 Federico Raimondi2,3 Barbara Bottazzi4 Diego Ripamonti5 Ivano Riva6 Francesco Landi1,7 Leonardo Alborghetti5 Marco Frigeni1 Marianna Damiani6,8 Caterina Micò1 Stefano Fagiuoli9 Ferdinando Luca Lorini6 Lucia Gandini6,8 Luca Novelli 2 Jonathan P. Morgan10 Benjamin M. J. Owens10 Karan J. K. Kanhai10 Gordana Tonkovic Reljanovic11 Marco Rizzi5 Fabiano Di Marco 2,12 Alberto Mantovani3,13,14 Alessandro Rambaldi 1,15 ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● Received: 1 April 2021 / Accepted: 12 May 2021 / Published online: 24 May 2021 © The Author(s) 2021. This article is published with open access 1234567890();,: 1234567890();,: To the Editor: Severe coronavirus disease 2019 (COVID-19) is characterized by interstitial pneumonia/acute respiratory distress syndrome and hyperinflammation, with elevated levels of proinflammatory cytokines, such as interleukin-6 (IL-6), associated with mortality and patients requiring ventilator support [1–3]. Targeting the IL-6 signaling pathway has been identified as a potential strategy to mitigate the elevated cytokines and resulting hyperinflammation associated with COVID-19 [1]. Siltuximab is the first and only US Food and Drug Administration- and European Medicines Agency-approved monoclonal antibody that specifically binds to IL-6, thereby inactivating IL-6–induced signaling. Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41375021-01299-x. Siltuximab is currently approved for the treatment of adults with idiopathic multicentric Castleman disease [4]. The aim of this study was to examine the association between siltuximab treatment, serum cytokine and chemokine levels, and mortality and/or respiratory function in hospitalized patients with COVID-19 and acute respiratory distress syndrome. We designed a prospective, observational cohort study at the start of the pandemic in response to the urgent unmet need for an effective treatment for patients with SARS-CoV-2 pneumonia, hyperinflammation, and respiratory failure [5]. In accordance with clinical guidelines developed at the Papa Giovanni XXIII Hospital in Bergamo, Italy, siltuximab was initially supplied under a compassionate-use program for the emergency treatment of 30 patients with severe COVID-19 requiring ventilatory support. Consequently, an investigator-initiated study protocol was developed for immediate implementation. The study protocol was submitted and approved through the Hospital Ethics Board. Patients, or * Giuseppe Gritti g.gritti@asst-pg23.it 8 Postgraduate School of Anesthesiology and Intensive Care, University of Milan, Milan, Italy 1 Hematology Unit, Azienda Socio Sanitario Territoriale Papa Giovanni XXIII, Bergamo, Italy 9 Gastroenterology Unit, Azienda Socio Sanitario Territoriale Papa Giovanni XXIII, Bergamo, Italy 2 Pneumology Unit, Azienda Socio Sanitario Territoriale Papa Giovanni XXIII, Bergamo, Italy 10 EUSA Pharma, Hemel Hempstead, UK 11 ErgoMed PLC, Guildford, UK Postgraduate School of Respiratory Medicine, University of Milan, Milan, Italy 12 Department of Health Sciences, University of Milan, Milan, Italy 13 Department of Biomedical Sciences, Humanitas University, Milan,..
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AR reports consultancy fees ' 'from Amgen, Celgene, Gilead, Italfarmaco, Novartis, Omeros, Pfizer, and Roche; ' 'travel support from Amgen, Celgene, Gilead, Italfarmaco, Novartis, and Roche; ' 'and research grants from Amgen, Italfarmaco, and Roche. CM reports travel ' 'support from Medac. DR reports personal fees from Gilead, Janssen, and ViiV. ' 'FDM reports grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and ' 'Novartis; and personal fees from Almirall, AstraZeneca, Boehringer Ingelheim, ' 'Chiesi, GlaxoSmithKline, Guidotti/Malesci, Menarini, Mundipharma, Novartis, ' 'Teva, and Zambon. GG reports non-financial support from Gilead Kite, Janssen, ' 'Roche, and Takeda; and personal fees from Amgen, Autolus, Gilead Kite, ' 'Italfarmaco, IQVIA, Roche, and Takeda. IR reports travel support from ' 'Aferetica. SF reports grants from Gilead and Novartis; and personal fees from ' 'AbbVie, Astellas, Bayer, Gilead, Intercept, Kedrion, Merck Sharp & Dohme, and ' 'Novartis. BB and AM are inventors of patents on PTX3 and obtain royalties on ' 'related reagents. The other authors declare no competing interests.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Conflict of interest'}}, { 'value': 'We complied with all relevant ethical rules. The protocol and informed consent ' 'forms were approved by the Hospital Ethics Board at the Papa Giovanni XXIII ' 'Hospital in Bergamo, Italy. Patients, or their legal representative, provided ' 'either verbal or written consent to participate in the study.', 'order': 3, 'name': 'Ethics', 'group': { 'name': 'EthicsHeading', 'label': 'Ethics approval and consent to participate'}}]}
Late treatment
is less effective
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