Anakinra efficacy in COVID-19 pneumonia guided by soluble urokinase plasminogen activator receptor: Association with the inflammatory burden of the host
Year: 2024
Type: article
Study design: Clinical Trial
Abstract: BACKGROUND: Anakinra was approved by the European Medicines Agency and received Emergency Use Authorization by the United States Food and Drug Administration for patients with COVID-19 pneumonia at risk for severe respiratory failure (SRF) with blood levels of soluble urokinase plasminogen activator receptor (suPAR) ≥ 6 ng/mL. We report the final results of the phase II open-label single-arm SAVE trial in a large population. METHODS: Patients with COVID-19 pneumonia and suPAR levels ≥ 6 ng/mL received subcutaneous anakinra 100 mg once daily for 10 days. The primary outcome was the incidence of SRF by day 14. Secondary outcomes were 30-day mortality, incidence of SRF according to time delay for start of treatment, safety, and associations with the inflammatory burden of the host. RESULTS: From March 2020 to March 2022, a total of 992 patients were enrolled. The incidence of SRF was 18.8%, similar to the results of the phase III pivotal SAVE-MOREtrial. The overall 30-day mortality was 9.5%. Participants were divided into 4 subgroups according to time delay between symptoms onset and start of anakinra. The incidence of SRF was similar for all subgroups. Serious adverse events were reported in 15.4%; only 3 were possibly related to anakinra. The most common adverse event was increased liver function tests. A post hoc comparison with the pivotal phase III trial showed similar anakinra outcomes among patient subgroups by levels of inflammatory mediators and D-dimers. CONCLUSIONS: Results support the efficacy of anakinra as being similar to that of the pivotal registrational trial for COVID-19 pneumonia. The lack of a comparator group is a limitation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04357366.
Authors: Evdoxia Kyriazopoulou, Karolina Akinosoglou, Eleni Florou, Elli Kouriannidi, Artemis Bogosian, Olga Tsachouridou, Konstantinos N. Syrigos, Nikolaos Gatselis, Haralampos Milionis, Ilias C. Papanikolaou, Styliani Sympardi, Maria Dafni, Antonia Alevizou, Alexia-Vasiliki Amvrazi, Errika Alexandrou, Kyprianos Archontoulis, Katerina Argyraki, Zoi Alexiou, Yakinthi Georgiou, Dimitra Gkogka, Foteini Kyrailidi, Vassiliki Kalyva, Triantafilli Nikolopoulou, Sofia Ioannou, Petros Bakakos, Georgia Karathanassiou, Kyriakos Koklanos, Dionysios-Nikolaos Miletis, Anna-Maria Tili, Lampros Vakkas, Ioanna Vila, Periklis Panagopoulos, Michael Samarkos, George Chrysos, George N. Dalekos, Garyphallia Poulakou, Symeon Metallidis, Evangelos J. Giamarellos-Bourboulis
Institutions: National and Kapodistrian University of Athens, University of Patras, Hellenic Institute for the Study of Sepsis, Aristotle University of Thessaloniki, University Hospital of Larissa, General Hospital of Larisa, Greece, University of Ioannina, Corfu General Clinic, General Hospital of Athens G. Genimatas, Democritus University of Thrace, Tzaneion General Hospital
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,280
OpenAlex ID: W4405098224