ANAKINRA EFFICACY IN COVID-19 PNEUMONIA GUIDED BY SOLUBLE UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR: ASSOCIATION WITH THE INFLAMMATORY BURDEN OF THE HOST

Anakinra was approved by the European Medicines Agency and received Emergency Use Authorization by the Food and Drug Administration of the United States for patients with COVID-19 pneumonia at risk for severe respiratory failure (SRF) with blood levels of suPAR (soluble urokinase plasminogen activator receptor) ≥ 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 subcutaneously anakinra 100mg 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, 992 patients were enrolled. The incidence of SRF was 18.8% similar to the results of the phase III pivotal trial. The overall 30-day mortality was 9.5%. Participants were divided into four subgroups of 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 patients' subgroups by levels of inflammatory mediators and D-dimers. Results support similar efficacy of anakinra with the pivotal registrational trial for COVID-19 pneumonia. The lack of a comparator group is a limitation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04357366.