Anakinra in hospitalized non-intubated patients with coronavirus disease 2019: a Systematic review and meta-analysis

Barkas, Fotios; Ntekouan, S. Filippas; Kosmidou, Maria; Liberopoulos, Evangelos; Liontos, Angelos; Milionis, Haralampos

doi:10.1093/rheumatology/keab447

Cited by 42 publications

(38 citation statements)

References 40 publications

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“…Previous studies and a recent meta-analysis provided a rationale for the use of anakinra in COVID-19. 23 Anakinra treatment using soluble urokinase plasminogen activator receptor (sUPAR) to identify an at-risk group of patients for early targeting of IL-1 was effective in moderate COVID-19 in a recent study. 24 There are several possible explanations for our findings.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of Tocilizumab, Sarilumab, and Anakinra for critically ill patients with COVID-19 The REMAP-CAP COVID-19 Immune Modulation Therapy Domain Randomized Clinical Trial

Derde

2021

Preprint

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BACKGROUND: The interleukin-6 receptor antagonist tocilizumab improves outcomes in critically ill patients with coronavirus disease 2019 (COVID-19). However, the effectiveness of other immune modulating agents is unclear. METHODS: We evaluated four immunomodulatory agents in an ongoing international, multifactorial, adaptive platform trial. Adult participants with COVID-19 were randomized to receive tocilizumab, sarilumab, anakinra, or standard care (control). In addition, a small group (n=21) of participants were randomized to interferon-beta1a. The primary outcome was an ordinal scale combining in-hospital mortality (assigned -1) and days free of organ support to day 21. The trial used a Bayesian statistical model with pre-defined triggers for superiority, equivalence or futility. RESULTS: Statistical triggers for equivalence between tocilizumab and sarilumab; and for inferiority of anakinra to the other active interventions were met at a planned adaptive analysis. Of the 2274 critically ill participants enrolled, 972 were assigned to tocilizumab, 485 to sarilumab, 378 to anakinra and 418 to control. Median organ support-free days were 7 (interquartile range [IQR] -1, 16), 9 (IQR -1, 17), 0 (IQR -1, 15) and 0 (IQR -1, 15) for tocilizumab, sarilumab, anakinra and control, respectively. Median adjusted odds ratios were 1.46 (95%CrI 1.13, 1.87), 1.50 (95%CrI 1.13, 2.00), and 0.99 (95%CrI 0.74, 1.35) for tocilizumab, sarilumab and anakinra, yielding 99.8%, 99.8% and 46.6% posterior probabilities of superiority, respectively, compared to control. Median adjusted odds ratios for hospital survival were 1.42 (95%CrI 1.05,1.93), 1.51 (95%CrI 1.06, 2.20) and 0.97 (95%CrI 0.66, 1.40) for tocilizumab, sarilumab and anakinra respectively, compared to control, yielding 98.8%, 98.8% and 43.6% posterior probabilities of superiority, respectively, compared to control. All treatments appeared safe. CONCLUSIONS: In patients with severe COVID-19 receiving organ support, tocilizumab and sarilumab are similarly effective at improving survival and reducing duration of organ support. Anakinra is not effective in this population.

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Section: Discussionmentioning

confidence: 99%

Effectiveness of Tocilizumab, Sarilumab, and Anakinra for critically ill patients with COVID-19 The REMAP-CAP COVID-19 Immune Modulation Therapy Domain Randomized Clinical Trial

Derde

2021

Preprint

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“…Additionally, treatment with an IL-1 receptor antagonist has led to improvements in mortality in severe COVID-19 (ref. 79 ), and the NLRP3 inflammasome is considered an emerging target for COVID-19 (ref. 80 ).…”

Section: Immune System Dysregulation Associated With Aging and Severe Covid-19: Innate Immunitymentioning

confidence: 99%

SARS-CoV-2, COVID-19 and the aging immune system

et al. 2021

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The coronavirus disease 2019 (COVID-19) pandemic is a global health threat with particular risk for severe disease and death in older adults and in adults with age-related metabolic and cardiovascular disease. Recent advances in the science of aging have highlighted how aging pathways control not only lifespan but also healthspan -the healthy years of life. Here, we discuss the aging immune system and its ability to respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We specifically focus on the intersect of severe COVID-19 and immunosenescence to highlight pathways that may be determinant for the risk of complications and death following infection with SARS-CoV-2. New or adapted therapeutics that target agingassociated pathways may be important tools to reduce the burden of death and long-term disability caused by this pandemic. Proposed interventions aimed at immunosenescence could enhance immune function not only in older adults but in susceptible younger individuals as well, ultimately improving complications of severe COVID-19 for all ages.

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“…3 CRS is characterized by a sharp increase of many proinflammatory cytokines, such as IL-1β, IL-6, Granulocyte-macrophage colony-stimulating factor (GM-CSF) and Tumor necrosis factor alpha (TNF-α), and elevated levels of D-dimers, ferritin and C-reactive protein (CRP). 4 Proposed immunomodulatory agents with potential use against the cytokine storm include glucocorticoids, 5 colchicine, 6 anakinra, 7 baricitinib 8 and sarilumab. 9 Antiviral drugs, such as remdesivir, 10 and monoclonal antibodies 11 are also used in selected cases.…”

Section: Introductionmentioning

confidence: 99%

Tocilizumab administration for the treatment of hospitalized patients with COVID‐19: A systematic review and meta‐analysis

et al. 2021

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Tocilizumab has been repurposed against the 'cytokine storm' in the setting of coronavirus disease 2019 . Our aim was to evaluate the efficacy of tocilizumab in the management of hospitalized COVID-19 patients. We searched MEDLINE, CENTRAL and medRxiv for studies of tocilizumab in hospitalized COVID-19 patients. Primary objective was the effectiveness of tocilizumab on mortality. Secondary objectives included the need for invasive mechanical ventilation (IMV), composite endpoints of mortality or IMV and intensive care unit (ICU) admission or IMV, length of hospitalization and differences in mortality in subgroups (ICU and non-ICU patients and patients receiving or not receiving concomitant corticosteroids). We included 52 studies (nine randomized controlled trials [RCTs] and 43 observational) with a total of 27,004 patients. In both RCTs and observational studies, the use of tocilizumab was associated with a reduction in mortality; 11% in RCTs (risk ratio [RR] 0.89, 95% CI 0.82 to 0.96) and 31% in observational studies (RR 0.69, 95% CI 0.58 to 0.83). The need for IMV was reduced by 19% in RCTs (RR 0.81, 95% CI 0.71 to 0.93), while no significant reduction was observed in observational studies. Both RCTs and observational studies showed a benefit from tocilizumab on the composite endpoint of mortality or IMV. Tocilizumab improved mortality both in ICU and non-ICU patients. Reduction in mortality was evident in observational studies regardless of the use of systemic corticosteroids, while that was not the case in the RCTs. Tocilizumab was associated with lower mortality and other clinically relevant outcomes in hospitalized patients with moderate-to-critical COVID-19.

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Anakinra in hospitalized non-intubated patients with coronavirus disease 2019: a Systematic review and meta-analysis

Cited by 42 publications

References 40 publications

Effectiveness of Tocilizumab, Sarilumab, and Anakinra for critically ill patients with COVID-19 The REMAP-CAP COVID-19 Immune Modulation Therapy Domain Randomized Clinical Trial

Effectiveness of Tocilizumab, Sarilumab, and Anakinra for critically ill patients with COVID-19 The REMAP-CAP COVID-19 Immune Modulation Therapy Domain Randomized Clinical Trial

SARS-CoV-2, COVID-19 and the aging immune system

Tocilizumab administration for the treatment of hospitalized patients with COVID‐19: A systematic review and meta‐analysis

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