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

Kyriazopoulou, E.; Poulakou, G.; Milionis, H.; Metallidis, S.; Adamis, G.; Tsiakos, K.; Fragkou, A.; Rapti, A.; Damoulari, C.; Fantoni, M.; Kalomenidis, I.; Chrysos, G.; Angheben, A.; Kainis, I.; Alexiou, Z.; Castelli, F.; Serino, F. S.; Tsilika, M.; Bakakos, P.; Nicastri, E.; Tzavara, V.; Kostis, E.; Dagna, L.; Koufargyris, P.; Dimakou, K.; Savvanis, S.; Tzatzagou, G.; Chini, M.; Cavalli, Giulio.; Bassetti, M.; Katrini, K.; Kotsis, V.; Tsoukalas, G.; Selmi, C.; Bliziotis, I.; Samarkos, M.; Doumas, M.; Ktena, S.; Masgala, A.; Papanikolaou, I.; Kosmidou, M.; Myrodia, D. -M.; Argyraki, A.; Cardellino, C. S.; Koliakou, K.; Katsigianni, E. -I.; Rapti, V.; Giannitsioti, E.; Cingolani, A.; Micha, S.; Akinosoglou, K.; Liatsis-Douvitsas, O.; Symbardi, S.; Gatselis, N.; Mouktaroudi, M.; Ippolito, G.; Florou, E.; Kotsaki, A.; Netea, M. G.; Eugen-Olsen, J.; Kyprianou, M.; Panagopoulos, P.; Dalekos, G. N.; Giamarellos-Bourboulis, E. J.

doi:10.1038/s41591-021-01499-z

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−1, 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.

Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial / Kyriazopoulou, E.; Poulakou, G.; Milionis, H.; Metallidis, S.; Adamis, G.; Tsiakos, K.; Fragkou, A.; Rapti, A.; Damoulari, C.; Fantoni, M.; Kalomenidis, I.; Chrysos, G.; Angheben, A.; Kainis, I.; Alexiou, Z.; Castelli, F.; Serino, F. S.; Tsilika, M.; Bakakos, P.; Nicastri, E.; Tzavara, V.; Kostis, E.; Dagna, L.; Koufargyris, P.; Dimakou, K.; Savvanis, S.; Tzatzagou, G.; Chini, M.; Cavalli, Giulio.; Bassetti, M.; Katrini, K.; Kotsis, V.; Tsoukalas, G.; Selmi, C.; Bliziotis, I.; Samarkos, M.; Doumas, M.; Ktena, S.; Masgala, A.; Papanikolaou, I.; Kosmidou, M.; Myrodia, D. -M.; Argyraki, A.; Cardellino, C. S.; Koliakou, K.; Katsigianni, E. -I.; Rapti, V.; Giannitsioti, E.; Cingolani, A.; Micha, S.; Akinosoglou, K.; Liatsis-Douvitsas, O.; Symbardi, S.; Gatselis, N.; Mouktaroudi, M.; Ippolito, G.; Florou, E.; Kotsaki, A.; Netea, M. G.; Eugen-Olsen, J.; Kyprianou, M.; Panagopoulos, P.; Dalekos, G. N.; Giamarellos-Bourboulis, E. J.. - In: NATURE MEDICINE. - ISSN 1078-8956. - 27:10(2021), pp. 1752-1760. [10.1038/s41591-021-01499-z]