Anakinra in COVID-19: A step closer to the cure

Barkas, Fotios; Christaki, Eirini; Liberopoulos, Evangelos; Kosmidou, Maria; Milionis, Haralampos

doi:10.1016/j.ejim.2021.11.005

Cited by 6 publications

(6 citation statements)

References 11 publications

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“…While suPAR proved to be a reliable marker, it is although not widely available, which raises the need of finding other markers for patient stratification to guide targeted therapy with anakinra. 28 Some of the commonly inflammatory markers such as C-reactive or ferritin have been suggested in a meta-analysis of 8 observational and 1 randomized controlled trial as potentially useful markers for scope, but larger trials are needed to define the ideal biomarker for defining patient eligibility and the best time point to initiate anakinra therapy during the disease progression. 29 A Cochrane meta-analyses performed on the 4 RCTs available at the end of November 2021, and a review of the 9 published systematic reviews on anakinra in COVID-19, concluded that the evidence is not complete, as they have identified more than 16 RCT with no results available, including 4 terminated trials.…”

Section: Clinical Trialsmentioning

confidence: 99%

Anakinra—An Interleukin-1 Receptor Antagonist for COVID-19

Nguyen

Dima

Willett

2023

American Journal of Therapeutics

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Background:Coronavirus disease (COVID-19) caused by SARS-CoV-2 virus caused a global pandemic in 2019. There are limited pharmacologic options available. The Food and Drug Administration initiated an emergency use authorization process to expedite pharmacologic agents to treat COVID-19. There are several agents available through the emergency use authorization process, ritonavir-boosted nirmatrelvir, remdesivir, and baricitinib. Anakinra is an interleukin (IL)-1 receptor antagonist that exhibits properties in fighting against COVID-19.Mechanism of Action, Pharmacodynamics, and Pharmacokinetics:Anakinra is a recombinant IL-1 receptor antagonist. The epithelial cell damage that may occur with COVID-19 enhances the release of IL-1, which plays a central role in severe cases. Thus, drugs that inhibit the IL-1 receptor may be beneficial in the management of COVID-19. Anakinra has good bioavailability after subcutaneous injection and a half-life of up to 6 hours.Clinical Trials:The SAVE-MORE, double-blind, randomized controlled trial, phase 3 evaluated the efficacy and safety of anakinra. Anakinra 100 mg was given subcutaneously daily for up to 10 days in patients with moderate and severe COVID-19 and plasma suPAR ≥6 ng/mL. Anakinra group had a 50.4% fully recovered with no viral RNA detected on day 28 versus 26.5% for placebo, and more than 50% of relative decrease in mortality. A significantly decreased risk of worse clinical outcome was observed.Therapeutic Advance:COVID-19 causes global pandemic and a serious viral disease. There are limited therapy options to combat this deadly disease. Anakinra is an IL-1 receptor antagonist and shown to be effective for the treatment of COVID-19 in some trials but not others. Anakinra, the first in this class, seems to have a mix result for the treatment of COVID-19.

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Section: Clinical Trialsmentioning

confidence: 99%

Anakinra—An Interleukin-1 Receptor Antagonist for COVID-19

Nguyen

Dima

Willett

2023

American Journal of Therapeutics

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“…The use of this drug in patients affected by COVID-19 produces positive effects in controlling the cytokine storm, consequently reducing the risk of acute respiratory distress syndrome (ARDS) and respiratory and organ failure [ 68 ]. Various studies have been carried out on the use of this drug in COVID-19 patients and, interestingly, in one of them, Anakinra reduced the need for mechanical ventilation and mortality in patients with severe COVID-19 [ 69 ]. A further study, conducted in patients with COVID-19 and ARDS, showed that Anakinra (5 mg/kg twice daily) could be safely used in order to improve respiratory function [ 67 ].…”

Section: Interleukine Inhibitorsmentioning

confidence: 99%

Drugs for COVID-19: An Update

et al. 2022

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was the seventh known human coronavirus, and it was identified in Wuhan, Hubei province, China, in 2020. It caused the highly contagious disease called coronavirus disease 2019 (COVID-19), declared a global pandemic by the World Health Organization (WHO) on 11 March 2020. A great number of studies in the search of new therapies and vaccines have been carried out in these three long years, producing a series of successes; however, the need for more effective vaccines, therapies and other solutions is still being pursued. This review represents a tracking shot of the current pharmacological therapies used for the treatment of COVID-19.

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“…However, the use of glucocorticoids is limited due to potential complications—compromised innate immunity, glycemic variability, and the impairment of endogenous cortisol production [ 7 ]. Early treatment with recombinant IL-1 receptor antagonist anakinra was shown to reduce mortality rates in severe COVID-19 pneumonia [ 8 , 9 ]. At the same time, the IL-6 receptor antagonist tocilizumab failed to show apparent benefits [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Discovery of Nitro-azolo[1,5-a]pyrimidines with Anti-Inflammatory and Protective Activity against LPS-Induced Acute Lung Injury

et al. 2022

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Acute lung injury remains a challenging clinical condition, necessitating the development of novel, safe and efficient treatments. The prevention of macrophage M1-polarization is a viable venue to tackle excessive inflammation. We performed a phenotypic screening campaign to identify azolopyrimidine compounds that effectively inhibit LPS-induced NO synthesis and interleukin 6 (IL-6) secretion. We identified lead compound 9g that inhibits IL-6 secretion with IC50 of 3.72 µM without apparent cytotoxicity and with minimal suppression of macrophage phagocytosis in contrast to dexamethasone. In a mouse model of LPS-induced acute lung injury, 30 mg/kg i.p. 9g ameliorated anxiety-like behavior, inhibited IL-6 release, and limited neutrophil infiltration and pulmonary edema. A histological study confirmed the protective activity of 9g. Treatment with compound 9g prevented the migration of CD68+ macrophages and the incidence of hemorrhage. Hence, we have identified a promising pharmacological approach for the treatment of acute lung injury that may hold promise for the development of novel drugs against cytokine-mediated complications of bacterial and viral infections.

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Anakinra in COVID-19: A step closer to the cure

Cited by 6 publications

References 11 publications

Anakinra—An Interleukin-1 Receptor Antagonist for COVID-19

Anakinra—An Interleukin-1 Receptor Antagonist for COVID-19

Drugs for COVID-19: An Update

Discovery of Nitro-azolo[1,5-a]pyrimidines with Anti-Inflammatory and Protective Activity against LPS-Induced Acute Lung Injury

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