Patients administered anakinra did not meet a study’s primary endpoint of proportion of patients who did not need mechanical ventilation 15 days after starting treatment for severe COVID-19 pneumonia.
Anakinra was not found to be more effective at reducing the need for mechanical ventilation for patients with severe COVID-19 pneumonia or hyperinflammation compared to the standard of care (SoC), according to a study recently published in JAMA.
“This study failed to meet the meet the primary efficacy endpoint of preventing mechanical ventilation, although improved oxygenation in terms of ratio of partial pressure O2 (Po2) to fraction of inspired O2 (FiO2) (Po2/ FiO2) was found in the anakinra group,” the study authors wrote.
Secondary endpoints evaluated (Po2/ FiO2) from baseline to day 15, intensive care unit (ICU) admission, and time to mechanical ventilation or death. ICU and time to mechanical ventilation or death were not significantly improved among patients on anakinra therapy compared to those on standard therapy.
COVID-19 pneumonia can be associated with hyperinflammation or increased interleukin (IL)– 1/IL-6 cytokines that can lead to poor outcomes. Anakinra is an IL–1 receptor antagonist used to treat symptoms such as COVID-19 hyperinflammation. In limited studies, anakinra was found to reduce mortality and mechanical ventilation outcomes. The European Medicines Agency approved the drug for patients with COVID-19 pneumonia that could progress to severe respiratory failure and need supplemental oxygen; however, evidence remains limited.
Investigators in Spain conducted The Clinical Trial of the Use of Anakinra in Cytokine Storm Syndrome Secondary to COVID-19 (ANA-COVID-GEAS)—a randomized, multicenter, open-label phase 2/3 clinical trial— to evaluate the safety and efficacy of anakinra compared to SoC for patients with severe COVID-19 pneumonia and hyperinflammation. SoC included hydroxychloroquine, lopinavir-ritonavir, and/or azithromycin.
The data suggest that anakinra did not significantly improve mortality outcomes or the need for mechanical ventilation among patients with COVID-19 pneumonia and hyperinflammation.
Among 92 patients in the anakinra cohort, an insignificant amount required mechanical ventilation compared to 87 in the SoC group (64 vs. 67 patients). However, anakinra is suggested to have a better antibiotic effect, as a greater number of participants treated with anakinra normal chest imaging at day 15.
Adverse events (AEs) occurred at a similar rate in both cohorts, with 12 patients developing infusion-related reactions and no patients developing neutropenia. The proportion of patients with at least 1 serious AE was the same between groups, with 4 patients experiening at least 1 serious AE associated with anakinra.
The most common serious AE was respiratory failure, which was observed in 4 patients in the anakinra group and in 7 patients in the SoC group. Acute respiratory distress syndrome was observed in 5 patients in the anakinra cohort and in 1 patient in the SoC cohort.
The study includes some limitations, the first of which being that it is an open-label design at risk of outcome bias. In addition, there are missing data, the authors did not account for the hospital effect, the anakinra group was administered more oxygen at baseline, and a smaller sample size showed lower detectable differences between primary and secondary outcomes.
“Use of anakinra together with SoC does not prevent the need for mechanical ventilation or reduce mortality risk compared with SoC alone in hospitalized patients with severe COVID-19 pneumonia and hyperinflammation,” the study authors wrote. However, “anakinra may have a role as an early treatment for patients with less-severe disease and inflammation.”
Fanlo, P, Gracia-Tello B, Aizpuru E, et al. Efficacy and Safety of Anakinra Plus Standard of Care for Patients With Severe COVID-19. Accessed April 10, 2023. JAMA Netw Open. 2023; doi:10.1001/jamanetworkopen.2023.7243