An open label trial of anakinra to prevent respiratory failure in COVID-19

Evdoxia Kyriazopoulou; Periklis Panagopoulos; Symeon Metallidis; George N Dalekos; Garyphallia Poulakou; Nikolaos Gatselis; Eleni Karakike; Maria Saridaki; Georgia Loli; Aggelos Stefos; Danai Prasianaki; Sarah Georgiadou; Olga Tsachouridou; Vasileios Petrakis; Konstantinos Tsiakos; Maria Kosmidou; Vassiliki Lygoura; Maria Dareioti; Haralampos Milionis; Ilias C Papanikolaou; Karolina Akinosoglou; Dimitra-Melia Myrodia; Areti Gravvani; Aliki Stamou; Theologia Gkavogianni; Konstantina Katrini; Theodoros Marantos; Ioannis P Trontzas; Konstantinos Syrigos; Loukas Chatzis; Stamatios Chatzis; Nikolaos Vechlidis; Christina Avgoustou; Stamatios Chalvatzis; Miltiades Kyprianou; Jos Wm van der Meer; Jesper Eugen-Olsen; Mihai G Netea; Evangelos J Giamarellos-Bourboulis

doi:10.7554/eLife.66125

An open label trial of anakinra to prevent respiratory failure in COVID-19

Evdoxia Kyriazopoulou, Periklis Panagopoulos, Symeon Metallidis, George N Dalekos, Garyphallia Poulakou, Nikolaos Gatselis, Eleni Karakike, Maria Saridaki, Georgia Loli, Aggelos Stefos, Danai Prasianaki, Sarah Georgiadou, Olga Tsachouridou, Vasileios Petrakis, Konstantinos Tsiakos, Maria Kosmidou, Vassiliki Lygoura, Maria Dareioti, Haralampos Milionis, Ilias C PapanikolaouKarolina Akinosoglou, Dimitra-Melia Myrodia, Areti Gravvani, Aliki Stamou, Theologia Gkavogianni, Konstantina Katrini, Theodoros Marantos, Ioannis P Trontzas, Konstantinos Syrigos, Loukas Chatzis, Stamatios Chatzis, Nikolaos Vechlidis, Christina Avgoustou, Stamatios Chalvatzis, Miltiades Kyprianou, Jos Wm van der Meer, Jesper Eugen-Olsen, Mihai G Netea, Evangelos J Giamarellos-Bourboulis

Klinisk Forskningsafdeling AHH

141 Citationer (Scopus)

Abstract

Background: It was studied if early suPAR-guided anakinra treatment can prevent severe respiratory failure (SRF) of COVID-19.

Methods: A total of 130 patients with suPAR ≥6 ng/ml were assigned to subcutaneous anakinra 100 mg once daily for 10 days. Primary outcome was SRF incidence by day 14 defined as any respiratory ratio below 150 mmHg necessitating mechanical or non-invasive ventilation. Main secondary outcomes were 30-day mortality and inflammatory mediators; 28-day WHO-CPS was explored. Propensity-matched standard-of care comparators were studied.

Results: 22.3% with anakinra treatment and 59.2% comparators (hazard ratio, 0.30; 95% CI, 0.20-0.46) progressed into SRF; 30-day mortality was 11.5% and 22.3% respectively (hazard ratio 0.49; 95% CI 0.25-0.97). Anakinra was associated with decrease in circulating interleukin (IL)-6, sCD163 and sIL2-R; IL-10/IL-6 ratio on day 7 was inversely associated with SOFA score; patients were allocated to less severe WHO-CPS strata.

Conclusions: Early suPAR-guided anakinra decreased SRF and restored the pro-/anti-inflammatory balance.

Funding: This study was funded by the Hellenic Institute for the Study of Sepsis, Technomar Shipping Inc, Swedish Orphan Biovitrum, and the Horizon 2020 Framework Programme.

Clinical trial number: NCT04357366.

Originalsprog	Engelsk
Artikelnummer	e66125
Tidsskrift	eLife
Vol/bind	10
Sider (fra-til)	1-21
Antal sider	21
ISSN	2050-084X
DOI	https://doi.org/10.7554/eLife.66125
Status	Udgivet - 8 mar. 2021

Adgang til dokumentet

10.7554/eLife.66125

Andre filer og links

Link to publication in Scopus

Citationsformater

Kyriazopoulou, E., Panagopoulos, P., Metallidis, S., Dalekos, G. N., Poulakou, G., Gatselis, N., Karakike, E., Saridaki, M., Loli, G., Stefos, A., Prasianaki, D., Georgiadou, S., Tsachouridou, O., Petrakis, V., Tsiakos, K., Kosmidou, M., Lygoura, V., Dareioti, M., Milionis, H., ... Giamarellos-Bourboulis, E. J. (2021). An open label trial of anakinra to prevent respiratory failure in COVID-19. eLife, 10, 1-21. Artikel e66125. https://doi.org/10.7554/eLife.66125

Kyriazopoulou, E, Panagopoulos, P, Metallidis, S, Dalekos, GN, Poulakou, G, Gatselis, N, Karakike, E, Saridaki, M, Loli, G, Stefos, A, Prasianaki, D, Georgiadou, S, Tsachouridou, O, Petrakis, V, Tsiakos, K, Kosmidou, M, Lygoura, V, Dareioti, M, Milionis, H, Papanikolaou, IC, Akinosoglou, K, Myrodia, D-M, Gravvani, A, Stamou, A, Gkavogianni, T, Katrini, K, Marantos, T, Trontzas, IP, Syrigos, K, Chatzis, L, Chatzis, S, Vechlidis, N, Avgoustou, C, Chalvatzis, S, Kyprianou, M, van der Meer, JW, Eugen-Olsen, J, Netea, MG & Giamarellos-Bourboulis, EJ 2021, 'An open label trial of anakinra to prevent respiratory failure in COVID-19', eLife, bind 10, e66125, s. 1-21. https://doi.org/10.7554/eLife.66125

@article{c5efe98f32c04cd9baca3796ea70a25d,

title = "An open label trial of anakinra to prevent respiratory failure in COVID-19",

abstract = "Background: It was studied if early suPAR-guided anakinra treatment can prevent severe respiratory failure (SRF) of COVID-19.Methods: A total of 130 patients with suPAR ≥6 ng/ml were assigned to subcutaneous anakinra 100 mg once daily for 10 days. Primary outcome was SRF incidence by day 14 defined as any respiratory ratio below 150 mmHg necessitating mechanical or non-invasive ventilation. Main secondary outcomes were 30-day mortality and inflammatory mediators; 28-day WHO-CPS was explored. Propensity-matched standard-of care comparators were studied.Results: 22.3% with anakinra treatment and 59.2% comparators (hazard ratio, 0.30; 95% CI, 0.20-0.46) progressed into SRF; 30-day mortality was 11.5% and 22.3% respectively (hazard ratio 0.49; 95% CI 0.25-0.97). Anakinra was associated with decrease in circulating interleukin (IL)-6, sCD163 and sIL2-R; IL-10/IL-6 ratio on day 7 was inversely associated with SOFA score; patients were allocated to less severe WHO-CPS strata.Conclusions: Early suPAR-guided anakinra decreased SRF and restored the pro-/anti-inflammatory balance.Funding: This study was funded by the Hellenic Institute for the Study of Sepsis, Technomar Shipping Inc, Swedish Orphan Biovitrum, and the Horizon 2020 Framework Programme.Clinical trial number: NCT04357366.",

keywords = "Anakinra, COVID-19, Interleukin-10, Severe respiratory failure, SuPAR, Interleukin-6/blood, Humans, Middle Aged, Antigens, CD/blood, Male, Receptors, Urokinase Plasminogen Activator/blood, Incidence, Interleukin-10/blood, SARS-CoV-2, Injections, Subcutaneous, Aged, 80 and over, Female, COVID-19/drug therapy, Standard of Care, Treatment Outcome, Receptors, Cell Surface/blood, Respiration, Artificial, Respiratory Insufficiency/epidemiology, Anti-Inflammatory Agents/administration & dosage, Aged, Antigens, Differentiation, Myelomonocytic/blood, Interleukin 1 Receptor Antagonist Protein/administration & dosage",

author = "Evdoxia Kyriazopoulou and Periklis Panagopoulos and Symeon Metallidis and Dalekos, {George N} and Garyphallia Poulakou and Nikolaos Gatselis and Eleni Karakike and Maria Saridaki and Georgia Loli and Aggelos Stefos and Danai Prasianaki and Sarah Georgiadou and Olga Tsachouridou and Vasileios Petrakis and Konstantinos Tsiakos and Maria Kosmidou and Vassiliki Lygoura and Maria Dareioti and Haralampos Milionis and Papanikolaou, {Ilias C} and Karolina Akinosoglou and Dimitra-Melia Myrodia and Areti Gravvani and Aliki Stamou and Theologia Gkavogianni and Konstantina Katrini and Theodoros Marantos and Trontzas, {Ioannis P} and Konstantinos Syrigos and Loukas Chatzis and Stamatios Chatzis and Nikolaos Vechlidis and Christina Avgoustou and Stamatios Chalvatzis and Miltiades Kyprianou and {van der Meer}, {Jos Wm} and Jesper Eugen-Olsen and Netea, {Mihai G} and Giamarellos-Bourboulis, {Evangelos J}",

note = "{\textcopyright} 2021, Kyriazopoulou et al.",

year = "2021",

month = mar,

day = "8",

doi = "10.7554/eLife.66125",

language = "English",

volume = "10",

pages = "1--21",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications Ltd",

}

TY - JOUR

T1 - An open label trial of anakinra to prevent respiratory failure in COVID-19

AU - Kyriazopoulou, Evdoxia

AU - Panagopoulos, Periklis

AU - Metallidis, Symeon

AU - Dalekos, George N

AU - Poulakou, Garyphallia

AU - Gatselis, Nikolaos

AU - Karakike, Eleni

AU - Saridaki, Maria

AU - Loli, Georgia

AU - Stefos, Aggelos

AU - Prasianaki, Danai

AU - Georgiadou, Sarah

AU - Tsachouridou, Olga

AU - Petrakis, Vasileios

AU - Tsiakos, Konstantinos

AU - Kosmidou, Maria

AU - Lygoura, Vassiliki

AU - Dareioti, Maria

AU - Milionis, Haralampos

AU - Papanikolaou, Ilias C

AU - Akinosoglou, Karolina

AU - Myrodia, Dimitra-Melia

AU - Gravvani, Areti

AU - Stamou, Aliki

AU - Gkavogianni, Theologia

AU - Katrini, Konstantina

AU - Marantos, Theodoros

AU - Trontzas, Ioannis P

AU - Syrigos, Konstantinos

AU - Chatzis, Loukas

AU - Chatzis, Stamatios

AU - Vechlidis, Nikolaos

AU - Avgoustou, Christina

AU - Chalvatzis, Stamatios

AU - Kyprianou, Miltiades

AU - van der Meer, Jos Wm

AU - Eugen-Olsen, Jesper

AU - Netea, Mihai G

AU - Giamarellos-Bourboulis, Evangelos J

PY - 2021/3/8

Y1 - 2021/3/8

N2 - Background: It was studied if early suPAR-guided anakinra treatment can prevent severe respiratory failure (SRF) of COVID-19.Methods: A total of 130 patients with suPAR ≥6 ng/ml were assigned to subcutaneous anakinra 100 mg once daily for 10 days. Primary outcome was SRF incidence by day 14 defined as any respiratory ratio below 150 mmHg necessitating mechanical or non-invasive ventilation. Main secondary outcomes were 30-day mortality and inflammatory mediators; 28-day WHO-CPS was explored. Propensity-matched standard-of care comparators were studied.Results: 22.3% with anakinra treatment and 59.2% comparators (hazard ratio, 0.30; 95% CI, 0.20-0.46) progressed into SRF; 30-day mortality was 11.5% and 22.3% respectively (hazard ratio 0.49; 95% CI 0.25-0.97). Anakinra was associated with decrease in circulating interleukin (IL)-6, sCD163 and sIL2-R; IL-10/IL-6 ratio on day 7 was inversely associated with SOFA score; patients were allocated to less severe WHO-CPS strata.Conclusions: Early suPAR-guided anakinra decreased SRF and restored the pro-/anti-inflammatory balance.Funding: This study was funded by the Hellenic Institute for the Study of Sepsis, Technomar Shipping Inc, Swedish Orphan Biovitrum, and the Horizon 2020 Framework Programme.Clinical trial number: NCT04357366.

AB - Background: It was studied if early suPAR-guided anakinra treatment can prevent severe respiratory failure (SRF) of COVID-19.Methods: A total of 130 patients with suPAR ≥6 ng/ml were assigned to subcutaneous anakinra 100 mg once daily for 10 days. Primary outcome was SRF incidence by day 14 defined as any respiratory ratio below 150 mmHg necessitating mechanical or non-invasive ventilation. Main secondary outcomes were 30-day mortality and inflammatory mediators; 28-day WHO-CPS was explored. Propensity-matched standard-of care comparators were studied.Results: 22.3% with anakinra treatment and 59.2% comparators (hazard ratio, 0.30; 95% CI, 0.20-0.46) progressed into SRF; 30-day mortality was 11.5% and 22.3% respectively (hazard ratio 0.49; 95% CI 0.25-0.97). Anakinra was associated with decrease in circulating interleukin (IL)-6, sCD163 and sIL2-R; IL-10/IL-6 ratio on day 7 was inversely associated with SOFA score; patients were allocated to less severe WHO-CPS strata.Conclusions: Early suPAR-guided anakinra decreased SRF and restored the pro-/anti-inflammatory balance.Funding: This study was funded by the Hellenic Institute for the Study of Sepsis, Technomar Shipping Inc, Swedish Orphan Biovitrum, and the Horizon 2020 Framework Programme.Clinical trial number: NCT04357366.

KW - Anakinra

KW - COVID-19

KW - Interleukin-10

KW - Severe respiratory failure

KW - SuPAR

KW - Interleukin-6/blood

KW - Humans

KW - Middle Aged

KW - Antigens, CD/blood

KW - Male

KW - Receptors, Urokinase Plasminogen Activator/blood

KW - Incidence

KW - Interleukin-10/blood

KW - SARS-CoV-2

KW - Injections, Subcutaneous

KW - Aged, 80 and over

KW - Female

KW - COVID-19/drug therapy

KW - Standard of Care

KW - Treatment Outcome

KW - Receptors, Cell Surface/blood

KW - Respiration, Artificial

KW - Respiratory Insufficiency/epidemiology

KW - Anti-Inflammatory Agents/administration & dosage

KW - Aged

KW - Antigens, Differentiation, Myelomonocytic/blood

KW - Interleukin 1 Receptor Antagonist Protein/administration & dosage

UR - http://www.scopus.com/inward/record.url?scp=85103308795&partnerID=8YFLogxK

U2 - 10.7554/eLife.66125

DO - 10.7554/eLife.66125

M3 - Journal article

C2 - 33682678

SN - 2050-084X

VL - 10

SP - 1

EP - 21

JO - eLife

JF - eLife

M1 - e66125

ER -

An open label trial of anakinra to prevent respiratory failure in COVID-19

Abstract

Adgang til dokumentet

Andre filer og links

Fingeraftryk

Citationsformater