Efficacy of early anti-inflammatory treatment with high doses of intravenous anakinra with or without glucocorticoids in patients with severe COVID-19 pneumonia.
Aged
Aged, 80 and over
Anti-Inflammatory Agents
/ administration & dosage
C-Reactive Protein
/ metabolism
COVID-19
/ mortality
Cohort Studies
Disease Progression
Drug Administration Schedule
Female
Glucocorticoids
/ administration & dosage
Humans
Injections, Intravenous
Interleukin 1 Receptor Antagonist Protein
/ administration & dosage
Italy
/ epidemiology
Kaplan-Meier Estimate
Male
Methylprednisolone
/ administration & dosage
Middle Aged
Pandemics
Respiration, Artificial
Retrospective Studies
SARS-CoV-2
Treatment Outcome
COVID-19 Drug Treatment
COVID-19 pneumonia
IL-1
anakinra
early treatment
glucocorticoid
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
31
10
2020
revised:
30
12
2020
accepted:
22
01
2021
pubmed:
9
2
2021
medline:
16
4
2021
entrez:
8
2
2021
Statut:
ppublish
Résumé
IL-1 plays a pivotal role in the inflammatory response during cytokine storm syndromes. 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. 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. 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). 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.
Sections du résumé
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.
Identifiants
pubmed: 33556464
pii: S0091-6749(21)00171-8
doi: 10.1016/j.jaci.2021.01.024
pmc: PMC7865089
pii:
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Glucocorticoids
0
Interleukin 1 Receptor Antagonist Protein
0
C-Reactive Protein
9007-41-4
Methylprednisolone
X4W7ZR7023
Types de publication
Controlled Clinical Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1217-1225Informations de copyright
Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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