Kyriazopoulou Evdoxia, Akinosoglou Karolina, Florou Eleni, Kouriannidi Elli, Bogosian Artemis, Tsachouridou Olga, Syrigos Konstantinos N, Gatselis Nikolaos, Milionis Haralampos, Papanikolaou Ilias C, Sympardi Styliani, Dafni Maria, Alevizou Antonia, Amvrazi Alexia-Vasiliki, Alexandrou Errika, Archontoulis Kyprianos, Argyraki Katerina, Alexiou Zoi, Georgiou Yakinthi, Gkogka Dimitra, Kyrailidi Foteini, Kalyva Vassiliki, Nikolopoulou Triantafilli, Ioannou Sofia, Bakakos Petros, Karathanassiou Georgia, Koklanos Kyriakos, Miletis Dionysios-Nikolaos, Tili Anna-Maria, Vakkas Lampros, Vila Ioanna, Panagopoulos Periklis, Samarkos Michael, Chrysos George, Dalekos George N, Poulakou Garyphallia, Metallidis Symeon, Giamarellos-Bourboulis Evangelos J
Fourth Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Department of Internal Medicine, University of Patras, Rion, Greece.
Int J Antimicrob Agents. 2025 Jan;65(1):107405. doi: 10.1016/j.ijantimicag.2024.107405. Epub 2024 Dec 6.
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.
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.
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.
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.
ClinicalTrials.gov, NCT04357366.
阿那白滞素已获得欧洲药品管理局的批准，并获得美国食品药品监督管理局的紧急使用授权，用于患有新型冠状病毒肺炎且有严重呼吸衰竭（SRF）风险、可溶性尿激酶型纤溶酶原激活物受体（suPAR）血药浓度≥6 ng/mL的患者。我们报告了一项针对大量人群的II期开放标签单臂SAVE试验的最终结果。
新型冠状病毒肺炎且suPAR水平≥6 ng/mL的患者接受皮下注射阿那白滞素100 mg，每日一次，共10天。主要结局是第14天时SRF的发生率。次要结局包括30天死亡率、根据治疗开始时间延迟的SRF发生率、安全性以及与宿主炎症负担的相关性。
从2020年3月至2022年3月，共纳入992例患者。SRF的发生率为18.8%，与III期关键SAVE-MORE试验的结果相似。总体30天死亡率为9.5%。根据症状出现与开始使用阿那白滞素之间的时间延迟，将参与者分为4个亚组。所有亚组的SRF发生率相似。报告的严重不良事件发生率为15.4%；只有3例可能与阿那白滞素有关。最常见的不良事件是肝功能检查指标升高。与关键III期试验的事后比较显示，按炎症介质和D-二聚体水平划分的患者亚组中，阿那白滞素的疗效相似。
结果支持阿那白滞素的疗效与新型冠状病毒肺炎关键注册试验的疗效相似。缺乏对照组是一个局限性。
ClinicalTrials.gov，NCT04357366。
