Anakinra for severe forms of COVID-19: a cohort study

Abstract

Background Coronaviruses can induce the production of interleukin (IL)-1β, IL-6, tumour necrosis factor, and other cytokines implicated in autoinflammatory disorders. It has been postulated that anakinra, a recombinant IL-1 receptor antagonist, might help to neutralise the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related hyperinflammatory state, which is considered to be one cause of acute respiratory distress among patients with COVID-19. We aimed to assess the off-label use of anakinra in patients who were admitted to hospital for severe forms of COVID-19 with symptoms indicative of worsening respiratory function.Methods The Ana-COVID study included a prospective cohort from Groupe Hospitalier Paris Saint-Joseph (Paris, France) and a historical control cohort retrospectively selected from the Groupe Hospitalier Paris Saint-Joseph COVID cohort, which began on March 18, 2020. Patients were included in the prospective cohort if they were aged 18 years or older and admitted to Groupe Hospitalier Paris Saint-Joseph with severe COVID-19-related bilateral pneumonia on chest x-ray or lung CT scan. The other inclusion criteria were either laboratory-confirmed SARS-CoV-2 or typical lung infiltrates on a lung CT scan, and either an oxygen saturation of 93% or less under oxygen 6 L/min or more, or aggravation (saturation ≤93% under oxygen 3 L/min) with a loss of 3% of oxygen saturation in ambient air over the previous 24 h. The historical control group of patients had the same inclusion criteria. Patients in the anakinra group were treated with subcutaneous anakinra (100 mg twice a day for 72 h, then 100 mg daily for 7 days) as well as the standard treatments at the institution at the time. Patients in the historical group received standard treatments and supportive care. The main outcome was a composite of either admission to the intensive care unit (ICU) for invasive mechanical ventilation or death.The main analysis was done on an intention-to-treat basis (including all patients in the anakinra group who received at least one injection of anakinra). FindingsFrom March 24 to April 6, 2020, 52 consecutive patients were included in the anakinra group and 44 historical patients were identified in the Groupe Hospitalier Paris Saint-Joseph COVID cohort study. Admission to the ICU for invasive mechanical ventilation or death occurred in 13 (25%) patients in the anakinra group and 32 (73%) patients in the historical group (hazard ratio [HR] 0•22 [95% CI 0•11-0•41; p<0•0001). The treatment effect of anakinra remained significant in the multivariate analysis (HR 0•22 [95% CI 0•10-0•49]; p=0•0002). An increase in liver aminotransferases occurred in seven (13%) patients in the anakinra group and four (9%) patients in the historical group.Interpretation Anakinra reduced both need for invasive mechanical ventilation in the ICU and mortality among patients with severe forms of COVID-19, without serious side-effects. Confirmation of efficacy will require con trolled trials.

Anakinra After Corticosteroid and/or Tocilizumab Treatment in Patients with Severe COVID-19 Pneumonia and Moderate Hyperinflammation. A Retrospective Cohort Study.

“…This higher dose of anakinra was associated with a 24% rate of severe adverse effects and a 14% rate of infectious complications. In the present study, no patients had infectious complications, probably because of the lower dose of anakinra; this nding was also reported in a recent study [13] that used similar doses of anakinra.…”

An Antioxidant Enzyme Therapeutic for COVID‐19

“…[8] Treatment of hyperinflammation and immunosuppression are highly recommended to address the immediate need to reduce mortality. [2] Current immunosuppression options include steroids, [9] intravenous immunoglobulin, [10] selective cytokine blockade (e.g., anakinra [11] or tocilizumab [12] ), and Janus kinase inhibition. [13] In light of the findings that elevated levels of reactive oxygen species (ROS) is strongly correlated with inflammation, [14] oxidative injury, [15] as well as viral infection and replication, [16][17][18] we speculate that regu lating the ROS level in COVID-19 patients could be effective for the treatment of hyperinflammation, protection of tissues from oxidative injury, and repression of viral replication.…”

Immunomodulatory Therapeutic Proteins in COVID‐19: Current Clinical Development and Clinical Pharmacology Considerations

“…30 Another study on the off-label use of anakinra in 52 patients who were admitted to the hospital for severe forms of COVID-19 with symptoms indicative of worsening respiratory function showed that anakinra reduced both need for invasive mechanical ventilation in the ICU and mortality, without serious side effects. 31 Randomized, controlled trials are being conducted in patients with moderate to critical pneumonia associated with COVID-19 at intravenous doses up to 400 mg daily. Subcutaneous anakinra is being evaluated at 100 mg once daily or every 6 to 16 hours in patients with COVID-19.…”