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Effect of anakinra on mortality in patients with COVID-19: a systematic review and patient-level meta-analysis

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International Collaborative Group for Anakinra in COVID-19. / Effect of anakinra on mortality in patients with COVID-19 : a systematic review and patient-level meta-analysis. In: The Lancet Rheumatology. 2021 ; Vol. 3, No. 10. pp. e690-e697.

Bibtex

@article{9e7fa140dbdd414dac50f941a42bfc74,
title = "Effect of anakinra on mortality in patients with COVID-19: a systematic review and patient-level meta-analysis",
abstract = "Background: Anakinra might improve the prognosis of patients with moderate to severe COVID-19 (ie, patients requiring oxygen supplementation but not yet receiving organ support). We aimed to assess the effect of anakinra treatment on mortality in patients admitted to hospital with COVID-19.Methods: For this systematic review and individual patient-level meta-analysis, a systematic literature search was done on Dec 28, 2020, in Medline (PubMed), Cochrane, medRxiv, bioRxiv, and the ClinicalTrials.gov databases for randomised trials, comparative studies, and observational studies of patients admitted to hospital with COVID-19, comparing administration of anakinra with standard of care, or placebo, or both. The search was repeated on Jan 22, 2021. Individual patient-level data were requested from investigators and corresponding authors of eligible studies; if individual patient-level data were not available, published data were extracted from the original reports. The primary endpoint was mortality after 28 days and the secondary endpoint was safety (eg, the risk of secondary infections). This study is registered on PROSPERO (CRD42020221491).Findings: 209 articles were identified, of which 178 full-text articles fulfilled screening criteria and were assessed. Aggregate data on 1185 patients from nine studies were analysed, and individual patient-level data on 895 patients were provided from six of these studies. Eight studies were observational and one was a randomised controlled trial. Most studies used historical controls. In the individual patient-level meta-analysis, after adjusting for age, comorbidities, baseline ratio of the arterial partial oxygen pressure divided by the fraction of inspired oxygen (PaO2/FiO2), C-reactive protein (CRP) concentrations, and lymphopenia, mortality was significantly lower in patients treated with anakinra (38 [11%] of 342) than in those receiving standard of care with or without placebo (137 [25%] of 553; adjusted odds ratio [OR] 0·32 [95% CI 0·20-0·51]). The mortality benefit was similar across subgroups regardless of comorbidities (ie, diabetes), ferritin concentrations, or the baseline PaO2/FiO2. In a subgroup analysis, anakinra was more effective in lowering mortality in patients with CRP concentrations higher than 100 mg/L (OR 0·28 [95% CI 0·17-0·47]). Anakinra showed a significant survival benefit when given without dexamethasone (OR 0·23 [95% CI 0·12-0·43]), but not with dexamethasone co-administration (0·72 [95% CI 0·37-1·41]). Anakinra was not associated with a significantly increased risk of secondary infections when compared with standard of care (OR 1·35 [95% CI 0·59-3·10]).Interpretation: Anakinra could be a safe, anti-inflammatory treatment option to reduce the mortality risk in patients admitted to hospital with moderate to severe COVID-19 pneumonia, especially in the presence of signs of hyperinflammation such as CRP concentrations higher than 100 mg/L.Funding: Sobi.",
author = "Evdoxia Kyriazopoulou and Thomas Huet and Giulio Cavalli and Andrea Gori and Miltiades Kyprianou and Peter Pickkers and Jesper Eugen-Olsen and Mario Clerici and Francisco Veas and Gilles Chatellier and Gilles Kaplanski and Netea, {Mihai G} and Emanuele Pontali and Marco Gattorno and Raphael Cauchois and Emma Kooistra and Matthijs Kox and Alessandra Bandera and H{\'e}l{\`e}ne Beaussier and Davide Mangioni and Lorenzo Dagna and {van der Meer}, {Jos W M} and Giamarellos-Bourboulis, {Evangelos J} and Gilles Hayem and {International Collaborative Group for Anakinra in COVID-19}",
note = "{\textcopyright} 2021 Elsevier Ltd. All rights reserved.",
year = "2021",
month = oct,
doi = "10.1016/S2665-9913(21)00216-2",
language = "English",
volume = "3",
pages = "e690--e697",
journal = "The Lancet Rheumatology",
issn = "2665-9913",
publisher = "Lancet Publishing Group",
number = "10",

}

RIS

TY - JOUR

T1 - Effect of anakinra on mortality in patients with COVID-19

T2 - a systematic review and patient-level meta-analysis

AU - Kyriazopoulou, Evdoxia

AU - Huet, Thomas

AU - Cavalli, Giulio

AU - Gori, Andrea

AU - Kyprianou, Miltiades

AU - Pickkers, Peter

AU - Eugen-Olsen, Jesper

AU - Clerici, Mario

AU - Veas, Francisco

AU - Chatellier, Gilles

AU - Kaplanski, Gilles

AU - Netea, Mihai G

AU - Pontali, Emanuele

AU - Gattorno, Marco

AU - Cauchois, Raphael

AU - Kooistra, Emma

AU - Kox, Matthijs

AU - Bandera, Alessandra

AU - Beaussier, Hélène

AU - Mangioni, Davide

AU - Dagna, Lorenzo

AU - van der Meer, Jos W M

AU - Giamarellos-Bourboulis, Evangelos J

AU - Hayem, Gilles

AU - International Collaborative Group for Anakinra in COVID-19

N1 - © 2021 Elsevier Ltd. All rights reserved.

PY - 2021/10

Y1 - 2021/10

N2 - Background: Anakinra might improve the prognosis of patients with moderate to severe COVID-19 (ie, patients requiring oxygen supplementation but not yet receiving organ support). We aimed to assess the effect of anakinra treatment on mortality in patients admitted to hospital with COVID-19.Methods: For this systematic review and individual patient-level meta-analysis, a systematic literature search was done on Dec 28, 2020, in Medline (PubMed), Cochrane, medRxiv, bioRxiv, and the ClinicalTrials.gov databases for randomised trials, comparative studies, and observational studies of patients admitted to hospital with COVID-19, comparing administration of anakinra with standard of care, or placebo, or both. The search was repeated on Jan 22, 2021. Individual patient-level data were requested from investigators and corresponding authors of eligible studies; if individual patient-level data were not available, published data were extracted from the original reports. The primary endpoint was mortality after 28 days and the secondary endpoint was safety (eg, the risk of secondary infections). This study is registered on PROSPERO (CRD42020221491).Findings: 209 articles were identified, of which 178 full-text articles fulfilled screening criteria and were assessed. Aggregate data on 1185 patients from nine studies were analysed, and individual patient-level data on 895 patients were provided from six of these studies. Eight studies were observational and one was a randomised controlled trial. Most studies used historical controls. In the individual patient-level meta-analysis, after adjusting for age, comorbidities, baseline ratio of the arterial partial oxygen pressure divided by the fraction of inspired oxygen (PaO2/FiO2), C-reactive protein (CRP) concentrations, and lymphopenia, mortality was significantly lower in patients treated with anakinra (38 [11%] of 342) than in those receiving standard of care with or without placebo (137 [25%] of 553; adjusted odds ratio [OR] 0·32 [95% CI 0·20-0·51]). The mortality benefit was similar across subgroups regardless of comorbidities (ie, diabetes), ferritin concentrations, or the baseline PaO2/FiO2. In a subgroup analysis, anakinra was more effective in lowering mortality in patients with CRP concentrations higher than 100 mg/L (OR 0·28 [95% CI 0·17-0·47]). Anakinra showed a significant survival benefit when given without dexamethasone (OR 0·23 [95% CI 0·12-0·43]), but not with dexamethasone co-administration (0·72 [95% CI 0·37-1·41]). Anakinra was not associated with a significantly increased risk of secondary infections when compared with standard of care (OR 1·35 [95% CI 0·59-3·10]).Interpretation: Anakinra could be a safe, anti-inflammatory treatment option to reduce the mortality risk in patients admitted to hospital with moderate to severe COVID-19 pneumonia, especially in the presence of signs of hyperinflammation such as CRP concentrations higher than 100 mg/L.Funding: Sobi.

AB - Background: Anakinra might improve the prognosis of patients with moderate to severe COVID-19 (ie, patients requiring oxygen supplementation but not yet receiving organ support). We aimed to assess the effect of anakinra treatment on mortality in patients admitted to hospital with COVID-19.Methods: For this systematic review and individual patient-level meta-analysis, a systematic literature search was done on Dec 28, 2020, in Medline (PubMed), Cochrane, medRxiv, bioRxiv, and the ClinicalTrials.gov databases for randomised trials, comparative studies, and observational studies of patients admitted to hospital with COVID-19, comparing administration of anakinra with standard of care, or placebo, or both. The search was repeated on Jan 22, 2021. Individual patient-level data were requested from investigators and corresponding authors of eligible studies; if individual patient-level data were not available, published data were extracted from the original reports. The primary endpoint was mortality after 28 days and the secondary endpoint was safety (eg, the risk of secondary infections). This study is registered on PROSPERO (CRD42020221491).Findings: 209 articles were identified, of which 178 full-text articles fulfilled screening criteria and were assessed. Aggregate data on 1185 patients from nine studies were analysed, and individual patient-level data on 895 patients were provided from six of these studies. Eight studies were observational and one was a randomised controlled trial. Most studies used historical controls. In the individual patient-level meta-analysis, after adjusting for age, comorbidities, baseline ratio of the arterial partial oxygen pressure divided by the fraction of inspired oxygen (PaO2/FiO2), C-reactive protein (CRP) concentrations, and lymphopenia, mortality was significantly lower in patients treated with anakinra (38 [11%] of 342) than in those receiving standard of care with or without placebo (137 [25%] of 553; adjusted odds ratio [OR] 0·32 [95% CI 0·20-0·51]). The mortality benefit was similar across subgroups regardless of comorbidities (ie, diabetes), ferritin concentrations, or the baseline PaO2/FiO2. In a subgroup analysis, anakinra was more effective in lowering mortality in patients with CRP concentrations higher than 100 mg/L (OR 0·28 [95% CI 0·17-0·47]). Anakinra showed a significant survival benefit when given without dexamethasone (OR 0·23 [95% CI 0·12-0·43]), but not with dexamethasone co-administration (0·72 [95% CI 0·37-1·41]). Anakinra was not associated with a significantly increased risk of secondary infections when compared with standard of care (OR 1·35 [95% CI 0·59-3·10]).Interpretation: Anakinra could be a safe, anti-inflammatory treatment option to reduce the mortality risk in patients admitted to hospital with moderate to severe COVID-19 pneumonia, especially in the presence of signs of hyperinflammation such as CRP concentrations higher than 100 mg/L.Funding: Sobi.

UR - http://www.scopus.com/inward/record.url?scp=85115375956&partnerID=8YFLogxK

U2 - 10.1016/S2665-9913(21)00216-2

DO - 10.1016/S2665-9913(21)00216-2

M3 - Journal article

C2 - 34396156

VL - 3

SP - e690-e697

JO - The Lancet Rheumatology

JF - The Lancet Rheumatology

SN - 2665-9913

IS - 10

ER -

ID: 67246315