Continuous Intravenous Anakinra Infusion to Calm the Cytokine Storm in Macrophage Activation Syndrome

Monteagudo, Luke; Boothby, Aaron; Gertner, Elie

doi:10.1002/acr2.11135

Cited by 166 publications

(164 citation statements)

References 39 publications

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“…Anakinra, an IL-1 receptor antagonist that blocks the biologic activity of IL-1, is a promising agent in this setting since it has already been shown to be effective in severe sepsis complicated by CRS macrophage activation syndrome [29, 30]. Recently Monteagudo et al [31] reported 5 cases of a cytokine storm (2 with an identified viral trigger) in which continuous intravenous anakinra infusion resulted in prompt improvement in laboratory and clinical parameters. There are limited data with specific IL-1 blockers in patients with COVID-19.…”

Section: Cytokine-targeting Therapiesmentioning

confidence: 99%

Weathering the Cytokine Storm in COVID-19: Therapeutic Implications

et al. 2020

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Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged in Wuhan, Hubei-China, as responsible for the coronavirus disease 2019 (COVID-19) and then spread rapidly worldwide. While most individuals remain asymptomatic or develop only mild symptoms, approximately 5% develop severe forms of COVID-19 characterized by acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF) that usually require intensive-care support and often yield a poor prognosis. Summary: The pathophysiology of COVID-19 is far from being completely understood, and the lack of effective treatments leads to a sense of urgency to develop new therapeutic strategies based on pathophysiological assumptions. The exaggerated cytokine release in response to viral infection, a condition known as cytokine release syndrome (CRS) or cytokine storm, is emerging as the mechanism leading to ARDS and MOF in COVID-19, thus endorsing the hypothesis that properly timed

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Section: Cytokine-targeting Therapiesmentioning

confidence: 99%

Weathering the Cytokine Storm in COVID-19: Therapeutic Implications

et al. 2020

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“…Promisingly, IL-1 blockade was associated with decreased mortality ( 141 ). More recently, a study by Monteagudo et al showed that IL-1 inhibitors were also effective in calming cytokine storm in hemophagocytic lymphocytosis patients ( 142 ). Huet et al also published a cohort study of 52 critically ill SARS-CoV-2 patients given Anakinra (an IL-1-inhibitor) and supportive care, while a control group of 44 patients received only supportive care.…”

Section: Treatment Protocolsmentioning

confidence: 99%

SARS-CoV-2: Pathogenesis, and Advancements in Diagnostics and Treatment

et al. 2020

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The emergence and rapid spread of SARS-CoV-2 in December 2019 has brought the world to a standstill. While less pathogenic than the 2002–2003 SARS-CoV, this novel betacoronavirus presents a global threat due to its high transmission rate, ability to invade multiple tissues, and ability to trigger immunological hyperactivation. The identification of the animal reservoir and intermediate host were important steps toward slowing the spread of disease, and its genetic similarity to SARS-CoV has helped to determine pathogenesis and direct treatment strategies. The exponential increase in cases has necessitated fast and reliable testing procedures. Although RT-PCR remains the gold standard, it is a time-consuming procedure, paving the way for newer techniques such as serologic tests and enzyme immunoassays. Various clinical trials using broad antiviral agents in addition to novel medications have produced controversial results; however, the advancement of immunotherapy, particularly monoclonal antibodies and immune modulators is showing great promise in clinical trials. Non-orthodox medications such as anti-malarials have been tested in multiple institutions but definitive conclusions are yet to be made. Adjuvant therapies have also proven to be effective in decreasing mortality in the disease course. While no formal guidelines have been established, the multitude of ongoing clinical trials as a result of unprecedented access to research data brings us closer to halting the SARS-CoV-2 pandemic.

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“…Anakinra was shown to increase the survival rate in patients with sepsis who meet the criteria for MAS, and who had liver dysfunction and disseminated intravascular coagulation [8]. This drug has also been used to treat several rare syndromes characterized by hyperin ammation mediated by the altered regulation of cytokine responses [9] [10]. Several studies have reported the bene ts of anakinra as an initial treatment for patients with hyperin ammation associated with severe SARS CoV-2 infection [11] [12] [13] [14], although these studies did not focus on patients who failed to respond to corticosteroid pulses or tocilizumab therapy alone or in combination.…”

Section: Introductionmentioning

confidence: 99%

Anakinra After Corticosteroid and/or Tocilizumab Treatment in Patients with Severe COVID-19 Pneumonia and Moderate Hyperinflammation. A Retrospective Cohort Study.

Aomar-Millán

Salvatierra

Torres-Parejo

et al. 2020

Preprint

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Introduction: Little evidence appears to exists for the use of anakinra, a recombinant interleukin-1 receptor antagonist, after non-response to treatment with corticosteroids alone or combined with tocilizumab in patients with severe COVID-19 pneumonia and moderate hyperinflammatory state. Patients and Methods: A retrospective observational cohort study was carried out involving 143 patients with severe COVID-19 pneumonia and moderate hyperinflammation. They received standard therapy along with pulses of methylprednisolone (group 1) or methylprednisolone plus tocilizumab (group 2), with the possibility of receiving anakinra (group 3) according to protocol. The aim of this study was to assess the role of anakinra in the clinical course (death, admission to the intensive care ward) during the first 60 days after the first corticosteroid pulse. Clinical, laboratory, and imaging characteristics as well as infectious complications were also analyzed.Results: 74 patients (51.7%) in group 1, 59 (41.3%) patients in group 2, and 10 patients (7%) in group 3 were included. 8 patients (10.8%) in group 1 died, 6 (10.2%) in group 2, and 0 (0%) in group 3. After adjustment for age and clinical severity indices, treatment with anakinra was associated with a reduced risk of mortality (adjusted hazard ratio 0.518, 95% CI 0.265-0.910; p=0.0437). Patients in group 3 had a lower mean CD4 count after 3 days of treatment. No patients in this group presented infectious complications.Conclusions: In patients with moderate hyperinflammatory state associated with severe COVID-19 pneumonia, treatment with anakinra after non-response to corticosteroids or corticosteroids plus tocilizumab therapy may be an option for the management of these patients, and may improve their prognosis.

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Continuous Intravenous Anakinra Infusion to Calm the Cytokine Storm in Macrophage Activation Syndrome

Cited by 166 publications

References 39 publications

Weathering the Cytokine Storm in COVID-19: Therapeutic Implications

Weathering the Cytokine Storm in COVID-19: Therapeutic Implications

SARS-CoV-2: Pathogenesis, and Advancements in Diagnostics and Treatment

Anakinra After Corticosteroid and/or Tocilizumab Treatment in Patients with Severe COVID-19 Pneumonia and Moderate Hyperinflammation. A Retrospective Cohort Study.

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