4CPS-314 3 day course of low dose subcutaneous anakinra in patients with refractory moderate–severe COVID-19: a proof-of-concept study

• Published in: European journal of hospital pharmacy. Science and practice 2021-03, Vol.28 (Suppl 1), p.A71-A72
• Main Authors: Calvo-Aranda, E, Canamares-Orbis, I, Novella-Navarro, M, Martinez-Alcala, A, Ortega De La O, MC, Escobar-Rodriguez, I, Sanchez-Aranda, F
• Format: Article
• Language: English
• Subjects: Conflicts of interest; Coronaviruses; COVID-19; Laboratories; Patients; Pneumonia; Severe acute respiratory syndrome coronavirus 2; Ventilation
• ISSN: 2047-9956; 2047-9964
• DOI: 10.1136/ejhpharm-2021-eahpconf.146

Background and importanceMany patients with moderate–severe COVID-19 develop immune dysregulation characterised by marked activation of innate immunity, elevation of acute phase reactants and release of proinflammatory cytokines (eg, interleukin 1 (IL-1) and IL-6), thus creating a hyperinflammatory state.Aim and objectivesTo determine the feasibility and safety of fighting hyperinflammation in patients with refractory moderate–severe COVID-19 by using a 3 day course of low dose subcutaneous anakinra.Material and methodsA prospective study was conducted in two hospitals in Spain, from 1 April to 8 May 2020, of nine hospitalised patients refractory to standard-of-care treatment with laboratory confirmed SARS-CoV-2 infection, a clinical course of at least 5 days, radiological pneumonia and moderate–severe COVID-19 according to clinical/analytical criteria. Patients received a daily subcutaneous dose of anakinra 100 mg for 3 consecutive days. The primary outcome was radiological improvement 72 hours after the first administration, together with appropriate clinical and analytical changes according to a combined set of response criteria. Secondary outcomes included incidence of serious adverse events, mortality, need for invasive ventilation at days 3 and 14, and days of hospitalisation.ResultsAll patients (aged 48–88 years) had bilateral pneumonia and received hydroxychloroquine; 7 received azithromycin, 5 ceftriaxone, 3 cyclosporine, 2 lopinavir/ritonavir, 1 interferon and 6 corticosteroids. Anakinra was introduced between 1 and 17 days (median 8 days) after admission. Six patients reached the primary outcome at day 3. An improvement in the chest X-ray at day 3 was observed in 7 of the 9 patients, and no radiological worsening was recorded in the 2 other patients. Median SpO2 at baseline was 92% (IQR 88–95), with a significant improvement of 97% (IQR 96–98) (p=0.007) at day 3. Significant differences were also observed in various laboratory parameters between days 0 and 3. No serious adverse events were observed. On days 3 and 14, no patient had died and none required invasive ventilation. One patient died after 21 days of hospitalisation; the remaining 8 were discharged (length of stay 6–45 days).Conclusion and relevanceIn this study of patients with refractory moderate–severe COVID-19, a 3 day course of low dose subcutaneous anakinra was effective and safe, resulting in radiological, clinical and analytical improvement in most cases. These observations requ