tetano
Editor, Senior Moderator
Nat Med
. 2021 Sep 3.
doi: 10.1038/s41591-021-01499-z. Online ahead of print.
Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial
Evdoxia Kyriazopoulou[SUP] 1 [/SUP], Garyfallia Poulakou[SUP] 2 [/SUP], Haralampos Milionis[SUP] 3 [/SUP], Simeon Metallidis[SUP] 4 [/SUP], Georgios Adamis[SUP] 5 [/SUP], Konstantinos Tsiakos[SUP] 6 [/SUP], Archontoula Fragkou[SUP] 7 [/SUP], Aggeliki Rapti[SUP] 6 [/SUP], Christina Damoulari[SUP] 1 [/SUP], Massimo Fantoni[SUP] 8 [/SUP], Ioannis Kalomenidis[SUP] 9 [/SUP], Georgios Chrysos[SUP] 10 [/SUP], Andrea Angheben[SUP] 11 [/SUP], Ilias Kainis[SUP] 12 [/SUP], Zoi Alexiou[SUP] 13 [/SUP], Francesco Castelli[SUP] 14 [/SUP], Francesco Saverio Serino[SUP] 15 [/SUP], Maria Tsilika[SUP] 1 [/SUP], Petros Bakakos[SUP] 16 [/SUP], Emanuele Nicastri[SUP] 17 [/SUP], Vassiliki Tzavara[SUP] 18 [/SUP], Evangelos Kostis[SUP] 19 [/SUP], Lorenzo Dagna[SUP] 20 [/SUP], Panagiotis Koufargyris[SUP] 1 [/SUP], Katerina Dimakou[SUP] 21 [/SUP], Spyridon Savvanis[SUP] 7 [/SUP], Glykeria Tzatzagou[SUP] 22 [/SUP], Maria Chini[SUP] 23 [/SUP], Giulio Cavalli[SUP] 20 [/SUP], Matteo Bassetti[SUP] 24 [/SUP], Konstantina Katrini[SUP] 1 [/SUP], Vasileios Kotsis[SUP] 25 [/SUP], George Tsoukalas[SUP] 26 [/SUP], Carlo Selmi[SUP] 27 [/SUP], Ioannis Bliziotis[SUP] 28 [/SUP], Michael Samarkos[SUP] 29 [/SUP], Michael Doumas[SUP] 30 [/SUP], Sofia Ktena[SUP] 1 [/SUP], Aikaterini Masgala[SUP] 31 [/SUP], Ilias Papanikolaou[SUP] 32 [/SUP], Maria Kosmidou[SUP] 3 [/SUP], Dimitra-Melia Myrodia[SUP] 2 [/SUP], Aikaterini Argyraki[SUP] 33 [/SUP], Chiara Simona Cardellino[SUP] 11 [/SUP], Katerina Koliakou[SUP] 34 [/SUP], Eleni-Ioanna Katsigianni[SUP] 34 [/SUP], Vassiliki Rapti[SUP] 2 [/SUP], Efthymia Giannitsioti[SUP] 10 [/SUP], Antonella Cingolani[SUP] 8 [/SUP], Styliani Micha[SUP] 34 [/SUP], Karolina Akinosoglou[SUP] 35 [/SUP], Orestis Liatsis-Douvitsas[SUP] 34 [/SUP], Styliani Symbardi[SUP] 36 [/SUP], Nikolaos Gatselis[SUP] 37 [/SUP], Maria Mouktaroudi[SUP] 1 34 [/SUP], Giuseppe Ippolito[SUP] 17 [/SUP], Eleni Florou[SUP] 34 [/SUP], Antigone Kotsaki[SUP] 1 [/SUP], Mihai G Netea[SUP] 38 39 [/SUP], Jesper Eugen-Olsen[SUP] 40 [/SUP], Miltiades Kyprianou[SUP] 34 [/SUP], Periklis Panagopoulos[SUP] 41 [/SUP], George N Dalekos[SUP] 37 [/SUP], Evangelos J Giamarellos-Bourboulis[SUP] 42 43 [/SUP]
Affiliations
Abstract
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[SUP]-1[/SUP], 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26-0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P < 0.0001); the respective median decrease of Sequential Organ Failure Assessment (SOFA) score on day 7 from baseline was 0 and 1 points (OR = 0.63, P = 0.004). Twenty-eight-day mortality decreased (hazard ratio = 0.45, P = 0.045), and hospital stay was shorter.
. 2021 Sep 3.
doi: 10.1038/s41591-021-01499-z. Online ahead of print.
Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial
Evdoxia Kyriazopoulou[SUP] 1 [/SUP], Garyfallia Poulakou[SUP] 2 [/SUP], Haralampos Milionis[SUP] 3 [/SUP], Simeon Metallidis[SUP] 4 [/SUP], Georgios Adamis[SUP] 5 [/SUP], Konstantinos Tsiakos[SUP] 6 [/SUP], Archontoula Fragkou[SUP] 7 [/SUP], Aggeliki Rapti[SUP] 6 [/SUP], Christina Damoulari[SUP] 1 [/SUP], Massimo Fantoni[SUP] 8 [/SUP], Ioannis Kalomenidis[SUP] 9 [/SUP], Georgios Chrysos[SUP] 10 [/SUP], Andrea Angheben[SUP] 11 [/SUP], Ilias Kainis[SUP] 12 [/SUP], Zoi Alexiou[SUP] 13 [/SUP], Francesco Castelli[SUP] 14 [/SUP], Francesco Saverio Serino[SUP] 15 [/SUP], Maria Tsilika[SUP] 1 [/SUP], Petros Bakakos[SUP] 16 [/SUP], Emanuele Nicastri[SUP] 17 [/SUP], Vassiliki Tzavara[SUP] 18 [/SUP], Evangelos Kostis[SUP] 19 [/SUP], Lorenzo Dagna[SUP] 20 [/SUP], Panagiotis Koufargyris[SUP] 1 [/SUP], Katerina Dimakou[SUP] 21 [/SUP], Spyridon Savvanis[SUP] 7 [/SUP], Glykeria Tzatzagou[SUP] 22 [/SUP], Maria Chini[SUP] 23 [/SUP], Giulio Cavalli[SUP] 20 [/SUP], Matteo Bassetti[SUP] 24 [/SUP], Konstantina Katrini[SUP] 1 [/SUP], Vasileios Kotsis[SUP] 25 [/SUP], George Tsoukalas[SUP] 26 [/SUP], Carlo Selmi[SUP] 27 [/SUP], Ioannis Bliziotis[SUP] 28 [/SUP], Michael Samarkos[SUP] 29 [/SUP], Michael Doumas[SUP] 30 [/SUP], Sofia Ktena[SUP] 1 [/SUP], Aikaterini Masgala[SUP] 31 [/SUP], Ilias Papanikolaou[SUP] 32 [/SUP], Maria Kosmidou[SUP] 3 [/SUP], Dimitra-Melia Myrodia[SUP] 2 [/SUP], Aikaterini Argyraki[SUP] 33 [/SUP], Chiara Simona Cardellino[SUP] 11 [/SUP], Katerina Koliakou[SUP] 34 [/SUP], Eleni-Ioanna Katsigianni[SUP] 34 [/SUP], Vassiliki Rapti[SUP] 2 [/SUP], Efthymia Giannitsioti[SUP] 10 [/SUP], Antonella Cingolani[SUP] 8 [/SUP], Styliani Micha[SUP] 34 [/SUP], Karolina Akinosoglou[SUP] 35 [/SUP], Orestis Liatsis-Douvitsas[SUP] 34 [/SUP], Styliani Symbardi[SUP] 36 [/SUP], Nikolaos Gatselis[SUP] 37 [/SUP], Maria Mouktaroudi[SUP] 1 34 [/SUP], Giuseppe Ippolito[SUP] 17 [/SUP], Eleni Florou[SUP] 34 [/SUP], Antigone Kotsaki[SUP] 1 [/SUP], Mihai G Netea[SUP] 38 39 [/SUP], Jesper Eugen-Olsen[SUP] 40 [/SUP], Miltiades Kyprianou[SUP] 34 [/SUP], Periklis Panagopoulos[SUP] 41 [/SUP], George N Dalekos[SUP] 37 [/SUP], Evangelos J Giamarellos-Bourboulis[SUP] 42 43 [/SUP]
Affiliations
- PMID: 34480127
- DOI: 10.1038/s41591-021-01499-z
Abstract
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[SUP]-1[/SUP], 85.9% (n = 510) of whom were receiving dexamethasone. At day 28, the adjusted proportional odds of having a worse clinical status (assessed by the 11-point World Health Organization Clinical Progression Scale (WHO-CPS)) with anakinra, as compared to placebo, was 0.36 (95% confidence interval 0.26-0.50). The median WHO-CPS decrease on day 28 from baseline in the placebo and anakinra groups was 3 and 4 points, respectively (odds ratio (OR) = 0.40, P < 0.0001); the respective median decrease of Sequential Organ Failure Assessment (SOFA) score on day 7 from baseline was 0 and 1 points (OR = 0.63, P = 0.004). Twenty-eight-day mortality decreased (hazard ratio = 0.45, P = 0.045), and hospital stay was shorter.