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Anakinra combined with methylprednisolone in patients with severe COVID-19 pneumonia and hyperinflammation: An
Giorgio Bozzi1, Davide Mangioni2, Francesca Minoia3
1Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Infectious Disease Unit, Milan, Italy.
Background:
Immunomodulants have been proposed to mitigate severe acute respiratory syndrome coronavirus 2-induced cytokine storm, which drives acute respiratory distress syndrome in coronavirus disease 2019 (COVID-19).
Objective:
We sought to determine efficacy and safety of the association of IL-1 receptor antagonist anakinra plus methylprednisolone in severe COVID-19 pneumonia with hyperinflammation.
Methods:
A secondary analysis of prospective observational cohort studies was carried out at an Italian tertiary health care facility. COVID-19 patients consecutively hospitalized (February 25, 2020, to March 30, 2020) with hyperinflammation (ferritin ≥1000 ng/mL and/or C-reactive protein >10 mg/dL) and respiratory failure (oxygen therapy from 0.4 FiO2 Venturi mask to invasive mechanical ventilation) were evaluated to investigate the effect of high-dose anakinra plus methylprednisolone on survival. Patients were followed from study inclusion to day 28 or death. Crude and adjusted (sex, age, baseline PaO2:FiO2 ratio, Charlson index, baseline mechanical ventilation, hospitalization to inclusion lapse) risks were calculated (Cox proportional regression model).
Results:
A total of 120 COVID-19 patients with hyperinflammation (median age, 62 years; 80.0% males; median PaO2:FiO2 ratio, 151; 32.5% on mechanical ventilation) were evaluated. Of these, 65 were treated with anakinra and methylprednisolone and 55 were untreated historical controls. At 28 days, mortality was 13.9% in treated patients and 35.6% in controls (Kaplan-Meier plots, P = .005). Unadjusted and adjusted risk of death was significantly lower for treated patients compared with controls (hazard ratio, 0.33, 95% CI, 0.15-0.74, P = .007, and HR, 0.18, 95% CI, 0.07-0.50, P = .001, respectively). No significant differences in bloodstream infections or laboratory alterations were registered.
Conclusions:
Treatment with anakinra plus methylprednisolone may be a valid therapeutic option in COVID-19 patients with hyperinflammation and respiratory failure, also on mechanical ventilation. Randomized controlled trials including the use of either agent alone are needed to confirm these results.
Insights
Anakinra and methylprednisolone significantly reduced mortality in severe COVID-19 patients with hyperinflammation. This combination therapy shows promise for critically ill patients, including those on mechanical ventilation.
Area of Science:
- Critical Care Medicine
- Infectious Diseases
- Pharmacology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can trigger a cytokine storm, leading to acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19).
- Immunomodulatory agents are being investigated to manage hyperinflammation associated with severe COVID-19.
Purpose of the Study:
- To evaluate the efficacy and safety of combining anakinra (IL-1 receptor antagonist) with methylprednisolone.
- To assess the impact of this combination therapy on survival in severe COVID-19 pneumonia patients experiencing hyperinflammation and respiratory failure.
Main Methods:
- Secondary analysis of a prospective observational cohort study at an Italian tertiary healthcare facility.
- Inclusion criteria: COVID-19 patients with hyperinflammation (ferritin ≥1000 ng/mL and/or C-reactive protein >10 mg/dL) and respiratory failure requiring oxygen therapy or mechanical ventilation.
- Comparison of outcomes between patients treated with high-dose anakinra plus methylprednisolone and untreated historical controls, followed for 28 days.
Main Results:
- 120 patients evaluated; 65 treated with anakinra and methylprednisolone, 55 untreated controls.
- 28-day mortality was significantly lower in the treated group (13.9%) compared to controls (35.6%) (P=.005).
- Adjusted hazard ratio for death was 0.18 (95% CI, 0.07-0.50; P=.001) for treated patients. No significant differences in infections or laboratory alterations were noted.
Conclusions:
- Anakinra combined with methylprednisolone appears to be a viable therapeutic option for severe COVID-19 patients with hyperinflammation and respiratory failure.
- The combination therapy demonstrated a significant reduction in mortality, even in patients requiring mechanical ventilation.
- Further randomized controlled trials are necessary to confirm these findings and evaluate individual agent efficacy.
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