Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial.


Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
10 2021
Historique:
received: 22 06 2021
accepted: 10 08 2021
pubmed: 5 9 2021
medline: 27 10 2021
entrez: 4 9 2021
Statut: ppublish

Résumé

Early increase of soluble urokinase plasminogen activator receptor (suPAR) serum levels is indicative of increased risk of progression of coronavirus disease 2019 (COVID-19) to respiratory failure. The SAVE-MORE double-blind, randomized controlled trial evaluated the efficacy and safety of anakinra, an IL-1α/β inhibitor, in 594 patients with COVID-19 at risk of progressing to respiratory failure as identified by plasma suPAR ≥6 ng ml

Identifiants

pubmed: 34480127
doi: 10.1038/s41591-021-01499-z
pii: 10.1038/s41591-021-01499-z
pmc: PMC8516650
doi:

Substances chimiques

Interleukin 1 Receptor Antagonist Protein 0
Placebos 0
Receptors, Urokinase Plasminogen Activator 0

Types de publication

Clinical Trial, Phase III Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1752-1760

Commentaires et corrections

Type : CommentIn
Type : ErratumIn

Informations de copyright

© 2021. The Author(s).

Références

Rovina, N. et al. Soluble urokinase plasminogen activator receptor (suPAR) as an early predictor of severe respiratory failure in patients with COVID-19 pneumonia. Crit. Care 24, 187 (2020).
doi: 10.1186/s13054-020-02897-4
Azam, T. U. et al. Soluble urokinase receptor (suPAR) in COVID-19-related AKI. J. Am. Soc. Nephrol. 31, 2725–2735 (2021).
doi: 10.1681/ASN.2020060829
Renieris, G. et al. IL-1 mediates tissue specific inflammation and severe respiratory failure in Covid-19: clinical and experimental evidence. Preprint at medRxiv https://doi.org/10.1101/2021.04.09.21255190 (2021).
Rodrigues, T. S. et al. Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients. J. Exp. Med. 218, e20201707 (2021).
doi: 10.1084/jem.20201707
Kyriazopoulou, E. et al. An open label trial of anakinra to prevent respiratory failure in COVID-19. eLife 10, e66125 (2021).
doi: 10.7554/eLife.66125
Manson, J. J. et al. COVID-19-associated hyperinflammation and escalation of patient care: a retrospective longitudinal cohort study. Lancet Rheumatol. 2, e594–e602 (2020).
doi: 10.1016/S2665-9913(20)30275-7
Webb, B. J. et al. Clinical criteria for COVID-19-associated hyperinflammatory syndrome: a cohort study. Lancet Rheumatol. 2, e754–e763 (2020).
doi: 10.1016/S2665-9913(20)30343-X
Caricchio, R. et al. Preliminary predictive criteria for COVID-19 cytokine storm. Ann. Rheum. Dis. 80, 88–95 (2021).
doi: 10.1136/annrheumdis-2020-218323
RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 397, 1637–1645 (2021).
doi: 10.1016/S0140-6736(21)00676-0
Gordon, A. C. et al. Interleukin-6 receptor antagonists in critically ill patients with Covid-19. N. Engl. J. Med. 384, 1491–1502 (2021).
doi: 10.1056/NEJMoa2100433
Guimarães, P. O. et al. Tofacitinib in patients hospitalized with COVID-19 pneumonia. N. Engl. J. Med. 385, 406–415 (2021).
doi: 10.1056/NEJMoa2101643
Caricchio, R. et al. Effect of canakinumab vs placebo on survival without invasive ventilation in patients hospitalized with severe COVID-19. A randomized clinical trial. JAMA 236, 230–239 (2021).
doi: 10.1001/jama.2021.9508
Jamilloux, Y. et al. Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions. Autoimmun. Rev. 19, 102567 (2020).
doi: 10.1016/j.autrev.2020.102567
Bozzi, G. et al. Anakinra combined with methylprednisolone in patients with severe COVID-19 pneumonia and hyperinflammation: an observational cohort study. J. Allergy Clin. Immunol. 147, 561–566 (2021).
doi: 10.1016/j.jaci.2020.11.006
Cavalli, G. et al. Interleukin-1 and interleukin-6 inhibition compared with standard management in patients with COVID-19 and hyperinflammation: a cohort study. Lancet Rheumatol. 3, e253–e261 (2021).
doi: 10.1016/S2665-9913(21)00012-6
Kooistra, E. J. et al. Anakinra treatment in critically ill COVID-19 patients: a prospective cohort study. Crit. Care 24, 688 (2020).
doi: 10.1186/s13054-020-03364-w
Cauchois, R. et al. Early IL-1 receptor blockade in severe inflammatory respiratory failure complicating COVID-19. Proc. Natl Acad. Sci. USA 117, 18951–18953 (2020).
doi: 10.1073/pnas.2009017117
Pontali, E. et al. Efficacy of early anti-inflammatory treatment with high doses of intravenous anakinra with or without glucocorticoids in patients with severe COVID-19 pneumonia. J. Allergy Clin. Immunol. 147, 1217–1225 (2021).
doi: 10.1016/j.jaci.2021.01.024
Huet, T. et al. Anakinra for severe forms of COVID-19: a cohort study. Lancet Rheumatol. 2, e393–e400 (2020).
doi: 10.1016/S2665-9913(20)30164-8
CORIMUNO-19 Collaborative Group. Effect of anakinra versus usual care in adults in hospital with COVID-19 and mild-to-moderate pneumonia (CORIMUNO-ANA-1): a randomised controlled trial. Lancet Respir. Med. 9, 295–304 (2021).
doi: 10.1016/S2213-2600(20)30556-7
Balkhair, A. et al. Anakinra in hospitalized patients with severe COVID-19 pneumonia requiring oxygen therapy: results of a prospective, open-label, interventional study. Int. J. Infect. Dis. 103, 288–296 (2021).
doi: 10.1016/j.ijid.2020.11.149
Rosas, I. O. et al. Tocilizumab in hospitalized patients with severe Covid-19 pneumonia. N. Engl. J. Med. 384, 1503–1516 (2021).
doi: 10.1056/NEJMoa2028700
Salama, C. et al. Tocilizumab in patients hospitalized with Covid-19 pneumonia. N. Engl. J. Med. 384, 20–30 (2021).
doi: 10.1056/NEJMoa2030340
Stone, J. H. et al. Efficacy of tocilizumab in patients hospitalized with Covid-19. N. Engl. J. Med. 383, 2333–2344 (2020).
doi: 10.1056/NEJMoa2028836
Salvarani, C. et al. Effect of tocilizumab vs standard care on clinical worsening in patients hospitalized with COVID-19 pneumonia: a randomized clinical trial. JAMA Intern. Med. 181, 24–31 (2021).
doi: 10.1001/jamainternmed.2020.6615
Giamarellos-Bourboulis, E. J. et al. Complex immune dysregulation in COVID-19 patients with severe respiratory failure. Cell Host Microbe 27, 992–1000 (2020).
doi: 10.1016/j.chom.2020.04.009

Auteurs

Evdoxia Kyriazopoulou (E)

4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

Garyfallia Poulakou (G)

3rd Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

Haralampos Milionis (H)

1st Department of Internal Medicine, University of Ioannina, Medical School, Ioannina, Greece.

Simeon Metallidis (S)

1st Department of Internal Medicine, Aristotle University of Thessaloniki, Medical School, Thessaloniki, Greece.

Georgios Adamis (G)

1st Department of Internal Medicine, G. Gennimatas General Hospital of Athens, Athens, Greece.

Konstantinos Tsiakos (K)

2nd Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases, Athens, Greece.

Archontoula Fragkou (A)

Department of Internal Medicine, Elpis General Hospital, Athens, Greece.

Aggeliki Rapti (A)

2nd Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases, Athens, Greece.

Christina Damoulari (C)

4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

Massimo Fantoni (M)

Dipartimento Scienze di Laboratorio e Infettivologiche - Fondazione Policlinico Gemelli IRCCS, Roma, Italy.

Ioannis Kalomenidis (I)

1st Department of Critical Care and Pulmonary Medicine, Medical School, National and Kapodistrian University of Athens, Evangelismos General Hospital, Athens, Greece.

Georgios Chrysos (G)

2nd Department of Internal Medicine, Tzaneio General Hospital of Piraeus, Athens, Greece.

Andrea Angheben (A)

Department of Infectious Tropical Diseases and Microbiology, IRCSS Sacro Cuore Hospital, Negrar, Verona, Italy.

Ilias Kainis (I)

10th Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases of Athens, Athens, Greece.

Zoi Alexiou (Z)

2nd Department of Internal Medicine, Thriasio General Hospital of Eleusis, Athens, Greece.

Francesco Castelli (F)

Spedali Civili, Brescia ASST Spedali Civili Hospital, University of Brescia, Brescia, Italy.

Francesco Saverio Serino (FS)

Department of Internal Medicine, Hospital of Jesolo, Jesolo, Italy.

Maria Tsilika (M)

4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

Petros Bakakos (P)

1st Department of Chest Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

Emanuele Nicastri (E)

Department of Internal Medicine, Spallanzani Institute of Rome, Rome, Italy.

Vassiliki Tzavara (V)

1st Department of Internal Medicine, Korgialeneion-Benakeion General Hospital, Athens, Greece.

Evangelos Kostis (E)

Department of Therapeutics, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

Lorenzo Dagna (L)

Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS Ospedale San Raffaele & Vita-Salute San Raffaele University, Milan, Italy.

Panagiotis Koufargyris (P)

4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

Katerina Dimakou (K)

5th Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases, Athens, Greece.

Spyridon Savvanis (S)

Department of Internal Medicine, Elpis General Hospital, Athens, Greece.

Glykeria Tzatzagou (G)

1st Department of Internal Medicine, Papageorgiou General Hospital of Thessaloniki, Thessaloniki, Greece.

Maria Chini (M)

3rd Department of Internal Medicine and Infectious Diseases Unit, Korgialeneion-Benakeion General Hospital, Athens, Greece.

Giulio Cavalli (G)

Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS Ospedale San Raffaele & Vita-Salute San Raffaele University, Milan, Italy.

Matteo Bassetti (M)

Infectious Diseases Clinic, Ospedale Policlinico San Martino IRCCS and Department of Health Sciences, University of Genova, Genova, Italy.

Konstantina Katrini (K)

4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

Vasileios Kotsis (V)

3rd Department of Internal Medicine, Aristotle University of Thessaloniki, Medical School, Thessaloniki, Greece.

George Tsoukalas (G)

4th Department of Pulmonary Medicine, Sotiria General Hospital of Chest Diseases, Athens, Greece.

Carlo Selmi (C)

Department of Biomedical Sciences, Humanitas University, Milan, Italy & IRCCS Humanitas Research Hospital, Milan, Italy.

Ioannis Bliziotis (I)

1st Department of Internal Medicine, Asklepieio General Hospital of Voula, Athens, Greece.

Michael Samarkos (M)

1st Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

Michael Doumas (M)

2nd Department of Propedeutic Medicine, Aristotle University of Thessaloniki, Medical School, Thessaloniki, Greece.

Sofia Ktena (S)

4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

Aikaterini Masgala (A)

2nd Department of Internal Medicine, Konstantopouleio General Hospital, Athens, Greece.

Ilias Papanikolaou (I)

Department of Pulmonary Medicine, General Hospital of Kerkyra, Corfu, Greece.

Maria Kosmidou (M)

1st Department of Internal Medicine, University of Ioannina, Medical School, Ioannina, Greece.

Dimitra-Melia Myrodia (DM)

3rd Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

Aikaterini Argyraki (A)

Department of Internal Medicine, Sotiria General Hospital of Chest Diseases, Athens, Greece.

Chiara Simona Cardellino (CS)

Department of Infectious Tropical Diseases and Microbiology, IRCSS Sacro Cuore Hospital, Negrar, Verona, Italy.

Katerina Koliakou (K)

Hellenic Institute for the Study of Sepsis, Athens, Greece.

Eleni-Ioanna Katsigianni (EI)

Hellenic Institute for the Study of Sepsis, Athens, Greece.

Vassiliki Rapti (V)

3rd Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

Efthymia Giannitsioti (E)

2nd Department of Internal Medicine, Tzaneio General Hospital of Piraeus, Athens, Greece.

Antonella Cingolani (A)

Dipartimento Scienze di Laboratorio e Infettivologiche - Fondazione Policlinico Gemelli IRCCS, Roma, Italy.

Styliani Micha (S)

Hellenic Institute for the Study of Sepsis, Athens, Greece.

Karolina Akinosoglou (K)

Department of Internal Medicine, University of Patras, Rion, Greece.

Orestis Liatsis-Douvitsas (O)

Hellenic Institute for the Study of Sepsis, Athens, Greece.

Styliani Symbardi (S)

1st Department of Internal Medicine, Thriasio General Hospital of Eleusis, Athens, Greece.

Nikolaos Gatselis (N)

Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece.

Maria Mouktaroudi (M)

4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Hellenic Institute for the Study of Sepsis, Athens, Greece.

Giuseppe Ippolito (G)

Department of Internal Medicine, Spallanzani Institute of Rome, Rome, Italy.

Eleni Florou (E)

Hellenic Institute for the Study of Sepsis, Athens, Greece.

Antigone Kotsaki (A)

4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.

Mihai G Netea (MG)

Department of Internal Medicine and Center for Infectious Diseases, Radboud University, Nijmegen, The Netherlands.
Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.

Jesper Eugen-Olsen (J)

Department of Clinical Research, Copenhagen University Hospital, Amager and Hvidovre, Denmark.

Miltiades Kyprianou (M)

Hellenic Institute for the Study of Sepsis, Athens, Greece.

Periklis Panagopoulos (P)

2nd Department of Internal Medicine, Democritus University of Thrace, Medical School, Alexandroupolis, Greece.

George N Dalekos (GN)

Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece.

Evangelos J Giamarellos-Bourboulis (EJ)

4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece. egiamarel@med.uoa.gr.
Hellenic Institute for the Study of Sepsis, Athens, Greece. egiamarel@med.uoa.gr.

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