Patients diagnosed with COVID-19 and treated with anakinra: a real-world study in the USA

Carly Rich, Daniel Eriksson, Fabrizio Dolfi, Katarzyna Jablonska, Firas Dabbous, Jameel Nazir, Carly Rich, Daniel Eriksson, Fabrizio Dolfi, Katarzyna Jablonska, Firas Dabbous, Jameel Nazir

Abstract

Anakinra, a recombinant, non-glycosylated human interleukin (IL)-1 receptor antagonist, has been used in real-world clinical practice to manage hyperinflammation in coronavirus disease 2019 (COVID-19). This retrospective, observational study analyses US hospital inpatient data of patients diagnosed with moderate/severe COVID-19 and treated with anakinra between 1 April and 31 August 2020. Of the 119 patients included in the analysis, 63.9% were male, 48.6% were of black ethnicity, and the mean (standard deviation [SD]) age was 64.7 (12.5) years. Mean (SD) time from hospital admission to anakinra initiation was 7.3 (6.1) days. Following anakinra initiation, 73.1% of patients received antibiotics, 55.5% received antithrombotics, and 91.0% received corticosteroids. Overall, 64.7% of patients required intensive care unit (ICU) admittance, and 28.6% received mechanical ventilation following admission. Patients who did not require ICU admittance or who were discharged alive experienced a significantly shorter time between hospital admission and receiving anakinra treatment compared with those admitted to the ICU (5 vs. 8 days; P = 0.002) or those who died in hospital (6 vs. 9 days; P = 0.01). Patients with myocardial infarction or renal conditions were six times (P < 0.01) and three times (P = 0.01), respectively, more likely to die in hospital than be discharged alive. A longer time from hospital admission until anakinra treatment was associated with significantly higher mortality (P = 0.01). Findings from this real-world study suggest that a shorter time from hospital admission to anakinra treatment is associated with significantly lower ICU admissions and mortality among patients with moderate/severe COVID-19.

Keywords: COVID-19; anakinra; database studies; interleukin-1 receptor antagonist protein; real-world evidence.

© Crown copyright 2021.

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Graphical Abstract

References

    1. World Health Organisation. Coronavirus Disease (COVID-19) Situation Report—142 (10 June 2020). 2020. (August 2021, date last accessed).
    1. Centers for Disease Control and Prevention. Symptoms of Coronavirus. 2020. (August 2021, date last accessed).
    1. Peckham H, de Gruijter NM, Raine C, et al. . Male sex identified by global COVID-19 meta-analysis as a risk factor for death and ITU admission. Nat Commun 2020, 11, 6317.
    1. COVID-NET. Laboratory-Confirmed COVID-19-Associated Hospitalizations . 2020. (August 2021, date last accessed).
    1. Huang C, Wang Y, Li X, et al. . Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020, 395, 497–506.
    1. Yang X, Yu Y, Xu J, et al. . Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med 2020, 8, 475–81.
    1. Wang D, Hu B, Hu C, et al. . Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA 2020, 323, 1061–9.
    1. Wang H, Li X, Li T, et al. . The genetic sequence, origin, and diagnosis of SARS-CoV-2. Eur J Clin Microbiol Infect Dis 2020, 39, 1629–35.
    1. National Institutes of Health. Therapeutic Management of Adults with COVID-19. 2020. (August 2021, date last accessed).
    1. van de Veerdonk FL, Netea MG.. Blocking IL-1 to prevent respiratory failure in COVID-19. Crit Care 2020, 24, 445.
    1. Khadke S, Ahmed N, Ahmed N, et al. . Harnessing the immune system to overcome cytokine storm and reduce viral load in COVID-19: a review of the phases of illness and therapeutic agents. Virol J 2020, 17, 154.
    1. Ingraham NE, Lotfi-Emran S, Thielen BK, et al. . Immunomodulation in COVID-19. Lancet Respir Med 2020, 8, 544–6.
    1. Qin C, Zhou L, Hu Z, et al. . Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis 2020, 71, 762–8.
    1. National Institutes of Health. Immunomodulators Under Evaluation for the Treatment of COVID-19. 2021. (August 2021, date last accessed).
    1. Langer-Gould A, Smith JB, Gonzales EG, et al. . Early identification of COVID-19 cytokine storm and treatment with anakinra or tocilizumab. Int J Infect Dis 2020, 99, 291–7.
    1. Gritti G, Raimondi F, Ripamonti D, et al. . IL-6 Signalling Pathway Inactivation with Siltuximab in Patients with COVID-19 Respiratory Failure: An Observational Cohort Study. 2020. (June 2021, date last accessed).
    1. Della-Torre E, Campochiaro C, Cavalli G, et al. .; SARI-RAF Study Group; SARI-RAF Study Group Members. Interleukin-6 blockade with sarilumab in severe COVID-19 pneumonia with systemic hyperinflammation: an open-label cohort study. Ann Rheum Dis 2020, 79, 1277–85.
    1. SOBI. KINERET® (Anakinra) Injection, for Subcutaneous Use. 2020. (August 2021, date last accessed).
    1. European Medicines Agency. Kineret®—Summary of Product Characteristics. 2020. (August 2021, date last accessed).
    1. Cavalli G, De Luca G, Campochiaro C, et al. . Interleukin-1 blockade with high-dose anakinra in patients with COVID-19, acute respiratory distress syndrome, and hyperinflammation: a retrospective cohort study. Lancet Rheumatol 2020, 2, e325–31.
    1. Huet T, Beaussier H, Voisin O, et al. . Anakinra for severe forms of COVID-19: a cohort study. Lancet Rheumatol 2020, 2, e393–400.
    1. Bozzi G, Mangioni D, Minoia F, et al. . Anakinra combined with methylprednisolone in patients with severe COVID-19 pneumonia and hyperinflammation: an observational cohort study. J Allergy Clin Immunol 2021, 147, 561–6.e4.
    1. Kyriazopoulou E, Huet T, Cavalli G, et al. .; 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. Lancet Rheumatol 2021, 3, e690–7.
    1. Kyriazopoulou E, Poulakou G, Milionis H, et al. . Author correction: early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial. Nat Med 2021, 27, 1850.
    1. HealthVerity. The Single Platform for Privacy-Protected, High Governance Data Exchange. 2020. (August 2021, date last accessed).
    1. Zhou F, Yu T, Du R, et al. . Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020, 395, 1054–62.
    1. Pontali E, Volpi S, Antonucci G, et al. . Safety and efficacy of early high-dose IV anakinra in severe COVID-19 lung disease. J Allergy Clin Immunol 2020, 146, 213–5.
    1. Laura Pasina GC, Navalesia P, Sella N, et al. . Anakinra for patients with COVID-19: a meta-analysis of non-randomized cohort studies. Eur J Intern Med 2021, 86, 34–40.
    1. Bhatraju PK, Ghassemieh BJ, Nichols M, et al. . Covid-19 in critically ill patients in the Seattle region—case series. N Engl J Med 2020, 382, 2012–22.
    1. Wang Y, Lu X, Li Y, et al. . Clinical course and outcomes of 344 intensive care patients with COVID-19. Am J Respir Crit Care Med 2020, 201, 1430–4.
    1. Talasaz AH, Sadeghipour P, Kakavand H, et al. . Recent randomized trials of antithrombotic therapy for patients with COVID-19: JACC state-of-the-art review. J Am Coll Cardiol 2021, 77, 1903–21.
    1. Cavalli G, Colafrancesco S, Emmi G, et al. . Interleukin 1α: a comprehensive review on the role of IL-1α in the pathogenesis and treatment of autoimmune and inflammatory diseases. Autoimmun Rev 2021, 20, 102763.
    1. Dimopoulos G, de Mast Q, Markou N, et al. . Favorable anakinra responses in severe covid-19 patients with secondary hemophagocytic lymphohistiocytosis. Cell Host Microbe 2020, 28, 117–23.e1.
    1. Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK . COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020, 395, 1033–4.
    1. 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, 846–8.
    1. Cavalli G, Larcher A, Tomelleri A, et al. . Interleukin-1 and interleukin-6 inhibition compared with standard management in patients with COVID-19 and hyperinflammation: a cohort study. Lancet Rheumatol 2021, 3, e253–61.
    1. van Deuren RC, Arts P, Cavalli G, et al. . Impact of rare and common genetic variation in the interleukin-1 pathway on human cytokine responses. Genome Med 2021, 13, 94.
    1. Rodrigues S, de Sa G, Ishimoto Y, et al. . Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients. J Exp Med 2021, 218, e20201707.
    1. Renieris G, Karakike E, Gkavogianni T, Droggiti DE, Kafousopoulos D.. IL-1 Mediates Tissue Specific Inflammation and Severe Respiratory Failure in Covid-19: Clinical and Experimental Evidence . 2021. (October 2021, date last accessed).
    1. Kyriazopoulou E, Panagopoulos P, Metallidis S, et al. . An open label trial of anakinra to prevent respiratory failure in COVID-19. Elife 2021, 10, e66125.

Source: PubMed

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