Efficacy of early anti-inflammatory treatment with high doses of intravenous anakinra with or without glucocorticoids in patients with severe COVID-19 pneumonia - 05/04/21

Doi : 10.1016/j.jaci.2021.01.024

Emanuele Pontali, MD ^a,^{∗
These authors contributed equally to this work}, Stefano Volpi, MD, PhD ^b,^{∗
These authors contributed equally to this work}, Alessio Signori, PhD ^c, Giancarlo Antonucci, MD ^a, Marco Castellaneta, MD ^a, Davide Buzzi, MD ^a, Amedeo Montale, MD ^a, Marta Bustaffa, MD ^b, Alessia Angelelli, MD ^b, Roberta Caorsi, MD ^b, Elisa Giambruno, MD ^a, Nicoletta Bobbio, MD ^a, Marcello Feasi, MD ^a, Ilaria Gueli, MD ^b, Francesca Tricerri, MD ^a, Francesca Calautti, Pharm D ^a, Elio Castagnola, MD ^b, Andrea Moscatelli, MD ^b, Gian Andrea Rollandi, MD ^a, Angelo Ravelli, MD, Prof ^b, Giovanni Cassola, MD ^a,^{∗
These authors contributed equally to this work}, Maria Pia Sormani, PhD ^c,^d,^{∗
These authors contributed equally to this work}, Marco Gattorno, MD ^b,^⁎^{∗
These authors contributed equally to this work}
^a Ente Ospedaliero Ospedale Galliera, Genoa, Italy
^b IRCCS G. Gaslini, Genoa, Italy
^c Department of Health Sciences, Section of Biostatistics, University of Genoa, Italy
^d Ospedale Policlinico San Martino-IRCCS, Genoa, Italy

^∗Corresponding author: Marco Gattorno, MD, Center for Autoinflammatory Diseases and Immunodeficiencies, IRCCS G. Gaslini, 16145, Genova, Italy.Center for Autoinflammatory Diseases and ImmunodeficienciesIRCCS G. GasliniGenova16145Italy

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Abstract

Background

IL-1 plays a pivotal role in the inflammatory response during cytokine storm syndromes.

Objective

Our aim was to analyze the efficacy and safety of early anti-inflammatory treatment (AIT) with intravenous anakinra with or without glucocorticoids in coronavirus disease 2019 (COVID-19) pneumonia.

Methods

We performed a retrospective single-center cohort study of patients admitted for COVID-19 pneumonia from February 26 to April 29, 2020, to assess the efficacy of early AIT with intravenous anakinra (100 mg every 8 hours for 3 days, with tapering) alone or in combination with a glucocorticoid (intravenous methylprednisolone, 1-2 mg/kg daily, with tapering). The standard of care (SOC) treatment was hydroxychloroquine and/or azithromycin with or without antivirals and anticoagulants. Late rescue AIT with anakinra or tocilizumab was also evaluated. Treatment effect on overall survival was assessed by a propensity score–adjusted Cox model.

Results

A total of 128 patients were analyzed; 63 patients received early AIT (30 received anakinra alone and 33 received anakinra plus a glucocorticoid) at admission, and 65 patients did not receive early AIT and were used as controls; of the latter 65 patients, 44 received the SOC treatment alone and 21 received the SOC treatment plus late rescue AIT. After adjustment for all the unbalanced baseline covariates, early AIT reduced the hazard of mortality by 74% (adjusted hazard ratio [HR] = 0.26; P < .001). The effect was similar in patients receiving anakinra alone (adjusted HR = 0.28; P = .04) and anakinra plus a glucocorticoid (adjusted HR = 0.33; P = .07). Late rescue treatment did not show a significant advantage over SOC treatment alone (adjusted HR = 0.82; P = .70).

Conclusions

This study suggests, on a larger series of patients with COVID-19 pneumonia, the potential efficacy and safety of the early use of high doses of intravenous anakinra with or without glucocorticoids.

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Graphical abstract

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Key words : IL-1, anakinra, glucocorticoid, early treatment, COVID-19 pneumonia

Abbreviations used : AIT, COVID-19, CRP, Fio₂, HR, ICU, IPW, LDH, MAS, OS, PS, SARS-CoV-2, SOC

Plan

Methods

Patients

Outcomes and statistical analysis

Results

Patients

Mortality and progression to invasive mechanical ventilation

Behavior of the inflammatory and respiratory parameters and comparison between anakinra alone and anakinra plus a glucocorticoid in responding patients

Safety

Discussion

Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.

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Vol 147 - N° 4

P. 1217-1225 - avril 2021 Retour au numéro

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Efficacy of early anti-inflammatory treatment with high doses of intravenous anakinra with or without glucocorticoids in patients with severe COVID-19 pneumonia - 05/04/21

Abstract

Background

Objective

Methods

Results

Conclusions

Graphical abstract

Plan

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