Anakinra for patients with COVID-19: a meta-analysis of non-randomized cohort studies

doi:10.1016/j.ejim.2021.01.016

Meta-Analysis

. 2021 Apr:86:34-40.

doi: 10.1016/j.ejim.2021.01.016. Epub 2021 Feb 5.

Anakinra for patients with COVID-19: a meta-analysis of non-randomized cohort studies

Affiliations

¹ Institute of Anesthesia and Intensive Care, Azienda Ospedaliera Universitaria di Padova, Padova (Italy).
² Unit of Immunology, Rheumatology, Allergy, and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
³ Institute of Anesthesia and Intensive Care, Azienda Ospedaliera Universitaria di Padova, Padova (Italy); Department of Medicine (DIMED), University of Padova, Padova (Italy).
⁴ Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan (Italy). Electronic address: landoni.giovanni@hsr.it.
⁵ I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian.
⁶ V. Negovsky Reanimatology Research Institute, Petrovka str, 25, b.2, Moscow, Russia; Department of Anesthesiology and Intensive Care, First Moscow State Medical University, Moscow, Russia.
⁷ Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan (Italy).
⁸ Unit of Immunology, Rheumatology, Allergy, and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy; Faculty of Medicine, Vita-Salute San Raffaele University, Milan (Italy).

PMID: 33581979
PMCID: PMC7862887
DOI: 10.1016/j.ejim.2021.01.016

Meta-Analysis

Anakinra for patients with COVID-19: a meta-analysis of non-randomized cohort studies

Laura Pasin et al. Eur J Intern Med. 2021 Apr.

. 2021 Apr:86:34-40.

doi: 10.1016/j.ejim.2021.01.016. Epub 2021 Feb 5.

Authors

Affiliations

¹ Institute of Anesthesia and Intensive Care, Azienda Ospedaliera Universitaria di Padova, Padova (Italy).
² Unit of Immunology, Rheumatology, Allergy, and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.
³ Institute of Anesthesia and Intensive Care, Azienda Ospedaliera Universitaria di Padova, Padova (Italy); Department of Medicine (DIMED), University of Padova, Padova (Italy).
⁴ Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan (Italy). Electronic address: landoni.giovanni@hsr.it.
⁵ I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian.
⁶ V. Negovsky Reanimatology Research Institute, Petrovka str, 25, b.2, Moscow, Russia; Department of Anesthesiology and Intensive Care, First Moscow State Medical University, Moscow, Russia.
⁷ Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan (Italy).
⁸ Unit of Immunology, Rheumatology, Allergy, and Rare Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy; Faculty of Medicine, Vita-Salute San Raffaele University, Milan (Italy).

PMID: 33581979
PMCID: PMC7862887
DOI: 10.1016/j.ejim.2021.01.016

Abstract

Introduction: Severe COVID-19 cases have a detrimental hyper-inflammatory host response and different cytokine-blocking biologic agents were explored to improve outcomes. Anakinra blocks the activity of both IL-1α and IL‑1β and is approved for different autoinflammatory disorders, but it is used off-label for conditions characterized by an excess of cytokine production. Several studies on anakinra in COVID-19 patients reported positive effects. We performed a meta-analysis of all published evidence on the use of anakinra in COVID19 to investigate its effect on survival and need for mechanical ventilation.

Methods: We searched for any study performed on adult patients with acute hypoxemic failure related to 2019-nCoV infection, receiving anakinra versus any comparator. Primary endpoint was mortality at the longest available follow-up. Adverse effects, need for mechanical ventilation and discharge at home with no limitations were also analysed.

Results: Four observational studies involving 184 patients were included. Overall mortality of patients treated with anakinra was significantly lower than mortality in the control group (95% CI 0.14-0.48, p<0.0001). Moreover, patients treated with anakinra had a significantly lower risk of need for mechanical ventilation than controls (95% CI 0.250.74, p=0.002). No difference in adverse events and discharge at home with no limitations was observed. The Trial Sequential Analysis z-cumulative line reached the monitoring boundary for benefit and the required sample size.

Conclusions: Administration of anakinra in COVID-19 patients was safe and might be associated with reductions in both mortality and need for mechanical ventilation. Randomized clinical trials are warranted to confirm these findings.

Keywords: Anakinra; COVID-19; Meta-analysis; Mortality; SARS-CoV-2.

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Conflict of interest statement

None.

Figures

**Fig. 1**
Flow diagram for selection of articles.

**Fig. 3**
Forest plot for need for invasive mechanical ventilation.

See this image and copyright information in PMC

Comment in

Anakinra or tocilizumab for prevention of COVID-19 death? A big dilemma.
Patoulias D, Dimosiari A, Michailidis T. Patoulias D, et al. Eur J Intern Med. 2021 Aug;90:107-108. doi: 10.1016/j.ejim.2021.05.039. Epub 2021 Jun 5. Eur J Intern Med. 2021. PMID: 34158235 Free PMC article. No abstract available.

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References

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1. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:1033–1034. doi: 10.1016/S0140-6736(20)30628-0. - DOI - PMC - PubMed
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1. De Luca G, Cavalli G, Campochiaro C, Della-Torre E, Angelillo P, Tomelleri A. GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort study. Lancet Rheumatol. 2020 doi: 10.1016/S2665-9913(20)30170-3. - DOI - PMC - PubMed
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[1] WHO Coronavirus Disease . WHO Coronavirus Disease (COVID-19) Dashboard; 2021. COVID-19) Dashboard. https://covid19.who.int/, accessed February 7, 2021.

[2] WHO Coronavirus Disease . WHO Coronavirus Disease (COVID-19) Dashboard; 2021. COVID-19) Dashboard. https://covid19.who.int/, accessed February 7, 2021.

[3] Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:1033–1034. doi: 10.1016/S0140-6736(20)30628-0. - DOI - PMC - PubMed

[4] Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395:1033–1034. doi: 10.1016/S0140-6736(20)30628-0. - DOI - PMC - PubMed

[5] Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46:846–848. doi: 10.1007/s00134-020-05991-x. - DOI - PMC - PubMed

[6] Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46:846–848. doi: 10.1007/s00134-020-05991-x. - DOI - PMC - PubMed

[7] De Luca G, Cavalli G, Campochiaro C, Della-Torre E, Angelillo P, Tomelleri A. GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort study. Lancet Rheumatol. 2020 doi: 10.1016/S2665-9913(20)30170-3. - DOI - PMC - PubMed

[8] De Luca G, Cavalli G, Campochiaro C, Della-Torre E, Angelillo P, Tomelleri A. GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort study. Lancet Rheumatol. 2020 doi: 10.1016/S2665-9913(20)30170-3. - DOI - PMC - PubMed

[9] Thompson BT, Chambers RC, Liu KD. Acute respiratory distress syndrome. N Engl J Med. 2017;377:562–572. doi: 10.1056/NEJMra1608077. - DOI - PubMed

[10] Thompson BT, Chambers RC, Liu KD. Acute respiratory distress syndrome. N Engl J Med. 2017;377:562–572. doi: 10.1056/NEJMra1608077. - DOI - PubMed

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Anakinra for patients with COVID-19: a meta-analysis of non-randomized cohort studies

Affiliations

Anakinra for patients with COVID-19: a meta-analysis of non-randomized cohort studies

Authors

Affiliations

Abstract

Conflict of interest statement

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