Background Immunomodulants have been proposed to mitigate SARS-Cov-2-induced cytokine storm, which drives acute respiratory distress syndrome in COVID-19. Objective To determine efficacy and safety of the association of IL-1 receptor antagonist anakinra plus methylprednisolone in severe COVID-19 pneumonia with hyperinflammation. Methods Secondary analysis of prospective observational cohort studies at an Italian tertiary health-care facility. COVID-19 patients consecutively hospitalized (02/25/2020 to 03/30/2020), with hyperinflammation (ferritin ≥1000ng/mL and/or C-reactive protein >10mg/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 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=0.005). Unadjusted and adjusted risk of death was significantly lower for treated patients compared to controls (HR 0.33 (95%CI 0.15-0.74), p=0.007 and HR 0.18 (95%CI 0.07-0.50), p=0.001, 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 use of either agent alone are needed to confirm these results.

Anakinra combined with methylprednisolone in patients with severe COVID-19 pneumonia and hyperinflammation: an observational cohort study / G. Bozzi, D. Mangioni, F. Minoia, S. Aliberti, G. Grasselli, L. Barbetta, V. Castelli, E. Palomba, L. Alagna, A. Lombardi, R. Ungaro, C. Agostoni, M. Baldini, F. Blasi, M. Cesari, G. Costantino, A.L. Fracanzani, N. Montano, V. Monzani, A. Pesenti, F. Peyvandi, M. Sottocorno, A. Muscatello, G. Filocamo, A. Gori, A. Bandera. - In: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. - ISSN 0091-6749. - 27:1(2021), pp. 28-33. [10.1016/j.jaci.2020.11.006]

Anakinra combined with methylprednisolone in patients with severe COVID-19 pneumonia and hyperinflammation: an observational cohort study

D. Mangioni
Secondo
;
S. Aliberti
Conceptualization
;
G. Grasselli;A. Lombardi;R. Ungaro;C. Agostoni;F. Blasi;M. Cesari;G. Costantino;A.L. Fracanzani;N. Montano;A. Pesenti;F. Peyvandi;A. Gori;A. Bandera
2021

Abstract

Background Immunomodulants have been proposed to mitigate SARS-Cov-2-induced cytokine storm, which drives acute respiratory distress syndrome in COVID-19. Objective To determine efficacy and safety of the association of IL-1 receptor antagonist anakinra plus methylprednisolone in severe COVID-19 pneumonia with hyperinflammation. Methods Secondary analysis of prospective observational cohort studies at an Italian tertiary health-care facility. COVID-19 patients consecutively hospitalized (02/25/2020 to 03/30/2020), with hyperinflammation (ferritin ≥1000ng/mL and/or C-reactive protein >10mg/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 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=0.005). Unadjusted and adjusted risk of death was significantly lower for treated patients compared to controls (HR 0.33 (95%CI 0.15-0.74), p=0.007 and HR 0.18 (95%CI 0.07-0.50), p=0.001, 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 use of either agent alone are needed to confirm these results.
COVID-19; SARS-COV-2; anakinra; anti-interleukin 1; corticosteroids; hyperinflammation; immunomodulation; mechanical ventilation; methylprednisolone; respiratory failure
Settore MED/10 - Malattie dell'Apparato Respiratorio
Settore MED/09 - Medicina Interna
Settore MED/17 - Malattie Infettive
Settore MED/41 - Anestesiologia
Settore MED/38 - Pediatria Generale e Specialistica
19-nov-2020
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/791209
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