Use of Anakinra to Prevent Mechanical Ventilation in Severe COVID‐19: A Case Series

Abstract

Objective To report the clinical experience with anakinra in preventing mechanical ventilation in patients with coronavirus disease 2019 (COVID‐19), symptoms of cytokine storm syndrome, and acute hypoxemic respiratory failure. Methods To be included in this retrospective case series, patients must have had severe acute respiratory syndrome coronavirus 2 (SARS–CoV‐2), fever, ferritin levels >1,000 ng/ml with 1 additional laboratory marker of hyperinflammation, and acute hypoxemic respiratory failure. Acute hypoxemic respiratory failure was defined as requiring 15 liters of supplemental oxygen via a nonrebreather mask combined with 6‐liter nasal cannula or use of ≥95% oxygen by high‐flow nasal cannula. We excluded patients in whom there was suspicion of bacterial infection or who were receiving immunosuppressants. Subcutaneous anakinra was initiated at 100 mg every 6 hours and gradually tapered off completely. The primary outcome was the prevention of mechanical ventilation. Results Of the 14 patients who met the criteria, 11 patients received anakinra for a maximum of 19 days. Seven of the patients who started anakinra treatment ≤36 hours after onset of acute hypoxemic respiratory failure did not require mechanical ventilation, and all were discharged home. Four patients who started anakinra ≥4 days after onset of acute hypoxemic respiratory failure required mechanical ventilation. Of those, 3 patients were extubated (2 discharged home and 1 remained hospitalized), and 1 died. All 3 patients who met the criteria but did not receive anakinra required mechanical ventilation. Two patients were extubated (1 discharged home and 1 remained hospitalized), and 1 remained on mechanical ventilation. Conclusion Our data suggest that anakinra could be beneficial in treating COVID‐19 patients with evidence of cytokine storm syndrome when initiated early after onset of acute hypoxemic respiratory failure. Our patient selection and treatment approach should be considered for investigation in a clinical trial to determine the safety and efficacy of anakinra in treating patients with COVID‐19 and symptoms of cytokine storm syndrome.

Defining Kawasaki Disease and Pediatric Multi-Inflammatory Syndrome During SARS-CoV-2 Epidemic in Italy: Results From A National, Multicenter Survey.

“…We would suggest, in absence of stronger clinical evidence, that early treatment with both IVIG (2 gr/kg/day) and glucocorticoids (methylprednisone 2 mg/kg/day) is indicated in KawaCOVID patients; in our experience treatment with parenteral anakinra (from 2 mg/kg/day to 10 mg/kg/day) is indicated in those patients with rapid clinical worsening or if clinical improvement is not reached within 48 hours since starting IVIG and corticosteroids. Our hypothesis seems to be con rmed from Navallo-Millan et al, suggesting that anakinra could be bene cial in COVID-19 adult patients with evidence of cytokine storm syndrome when initiated early after the onset of Acute Hypoxic Respiratory Failure 22 .…”

Rheumatic Musculoskeletal Diseases and COVID-19 A Review of the First 6 Months of the Pandemic

“…Due to the pathophysiological similarities pertaining to the macrophage activation between HLH and the hyperinflammation seen in the second phase of COVID-19, a small number of patients have been treated with the IL-1 receptor antagonist anakinra. Two case series report anakinra treatment in 9 and 11 patients, respectively ( 131 , 132 ). Eight out of nine and seven out of 11 patients treated with anakinra did not require invasive ventilation.…”

Anakinra as rescue therapy to treat patients with severe COVID-19 refractory to tocilizumab

“…Thus, a 7-day course of anakinra did not suppose an added risk factor for bacterial superinfection in these non-intubated patients. The short half-live of anakinra (4 to 6 hours) and relatively short length of treatment may suppose an advantage compared with other biologic drugs such as IL-6 or TNF inhibitors in terms of preventing bacterial infection [5,15].…”