Anakinra as a potential alternative in the treatment of severe acute respiratory infection associated with SARS-CoV-2 refractory to tocilizumab

Figuero-Pérez, Luis; Olivares-Hernández, Alejandro; Cornejo, R.A. Escala; Terán-Brage, Eduardo; López-Gutiérrez, Álvaro; Cruz-Hernández, Juan J.

doi:10.1016/j.reumae.2020.06.008

Cited by 10 publications

(10 citation statements)

References 7 publications

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“…Strikingly, in the latter study, tocilizumab decreases hospital-related mortality (HR: 0.64, 95%CI 0.47–0.87; p = 0.040). Conversely, reports of tocilizumab failure for COVID-19 have also been reported [ 28 – 30 ], and, in another study of 21 patients (matched to a historical control group using propensity score matching), such beneficial effect of tocilizumab was not outlined [ 31 ]. Yet, it should be emphasized that in the latter study, all patients received high-dose methylprednisolone —which might have skewed the study results—and the levels of oxygen therapy were not specified.…”

Section: Discussionmentioning

confidence: 99%

Tocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis

et al. 2020

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Background High levels of serum interleukin-6 (IL-6) correlate with disease severity in COVID-19. We hypothesized that tocilizumab (a recombinant humanized anti-IL-6 receptor) could improve outcomes in selected patients with severe worsening COVID-19 pneumonia and high inflammatory parameters. Methods The TOCICOVID study included a prospective cohort of patients aged 16–80 years with severe (requiring > 6 L/min of oxygen therapy to obtain Sp02 > 94%) rapidly deteriorating (increase by ≥ 3 L/min of oxygen flow within the previous 12 h) COVID-19 pneumonia with ≥ 5 days of symptoms and C-reactive protein levels > 40 mg/L. They entered a compassionate use program of treatment with intravenous tocilizumab (8 mg/kg with a maximum of 800 mg per infusion; and if needed a second infusion 24 to 72 h later). A control group was retrospectively selected with the same inclusion criteria. Outcomes were assessed at D28 using inverse probability of treatment weighted (IPTW) methodology. Results Among the 96 patients included (81% male, mean (SD) age: 60 (12.5) years), underlying conditions, baseline disease severity, and concomitant medications were broadly similar between the tocilizumab ( n = 49) and the control ( n = 47) groups. In the IPTW analysis, treatment with tocilizumab was associated with a reduced need for overall ventilatory support (49 vs. 89%, wHR: 0.39 [0.25–0.56]; p < 0.001). Albeit lacking statistical significance, there was a substantial trend towards a reduction of mechanical ventilation (31% vs. 45%; wHR: 0.58 [0.36–0.94]; p = 0.026). However, tocilizumab did not improve overall survival (wHR = 0.68 [0.31–1.748], p = 0.338). Among the 85 (89%) patients still alive at D28, patients treated with tocilizumab had a higher rate of oxygen withdrawal (82% vs. 73.5%, wHR = 1.66 [1.17–2.37], p = 0.005), with a shorter delay before being weaned of oxygen therapy (mean 11 vs. 16 days; p < 0.001). At D28, the rate of patients discharged from hospital was higher in the tocilizumab group (70% vs. 40%, wHR = 1.82 [1.22–2.75]; p = 0.003). The levels of CRP and fibrinogen post therapy ( p < 0.001 for both variables) were significantly lower in the tocilizumab group (interaction test, mixed model). Rates of neutropenia (35% vs. 0%; p < 0.001) were higher in the tocilizumab group, yet rates of infections (22% vs. 38%, p = 0.089) including ventilator-acquired pneumonia (8% vs. 26%, p = 0.022) were higher in the control group. Conclusion These data could be helpful for the design of future trials aiming to counter COVID-19-induced inflammation, especially before patients require admission to the intensive ca...

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Section: Discussionmentioning

confidence: 99%

Tocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis

et al. 2020

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“…Of note, gene expression analyses concur with these findings, i.e., IL-1-related proinflammatory pathways are highly upregulated in severe cases ( 151 ). Therefore, the IL-1 blockade treatment by anakinra (an anti-IL-1 receptor antagonist) may be an effective alternative option for COVID-19 patients ( 152 ).…”

Section: Cytokine Secretion Induced By Sars-cov-2 Infectionmentioning

confidence: 99%

The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections

Hsu

Peng

et al. 2022

Front. Immunol.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in countless infections and caused millions of deaths since its emergence in 2019. Coronavirus disease 2019 (COVID-19)-associated mortality is caused by uncontrolled inflammation, aberrant immune response, cytokine storm, and an imbalanced hyperactive immune system. The cytokine storm further results in multiple organ failure and lung immunopathology. Therefore, any potential treatments should focus on the direct elimination of viral particles, prevention strategies, and mitigation of the imbalanced (hyperactive) immune system. This review focuses on cytokine secretions of innate and adaptive immune responses against COVID-19, including interleukins, interferons, tumor necrosis factor-alpha, and other chemokines. In addition to the review focus, we discuss potential immunotherapeutic approaches based on relevant pathophysiological features, the systemic immune response against SARS-CoV-2, and data from recent clinical trials and experiments on the COVID-19-associated cytokine storm. Prompt use of these cytokines as diagnostic markers and aggressive prevention and management of the cytokine storm can help determine COVID-19-associated morbidity and mortality. The prophylaxis and rapid management of the cytokine storm appear to significantly improve disease outcomes. For these reasons, this study aims to provide advanced information to facilitate innovative strategies to survive in the COVID-19 pandemic.

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“…A recent study reported autoantibodies to cytokines as a marker for disease severity in COVID-19 [74], which has interest because of previous associations of anticytokine antibodies to infectious disease susceptibility and outcomes. In addition, there is increasing evidence that several drugs, such as IL-6 antagonists, that have been used in patients with HLH, MAS and other autoimmune/autoinflammatory conditions were beneficial in COVID-19 [75][76][77][78][79][80][81][82][83][84][85][86][87][88]. Interestingly, autoimmune disease patients treated with anti-TNF alpha inhibitors do not show increased risk of COVID-19 infection or more severe disease cause [89].…”

Section: Link Between Covid-19 and Autoimmunitymentioning

confidence: 99%

Circulating Calprotectin as a Biomarker of COVID-19 Severity

Mähler

Meroni

Infantino

et al. 2021

Expert Review of Clinical Immunology

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Introduction: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although demographic and clinical parameters such as sex, age, comorbidities, genetic background and various biomarkers have been identified as risk factors, there is an unmet need to predict the risk and onset of severe inflammatory disease leading to poor clinical outcomes. In addition, very few mechanistic biomarkers are available to inform targeted treatment of severe (auto)-inflammatory conditions associated with COVID-19. Calprotectin, also known as S100A8/S100A9, MRP8/14 (Myeloid-Related Protein) or L1, is a heterodimer involved in neutrophil-related inflammatory processes. In COVID-19 patients, calprotectin levels were reported to be associated with poor clinical outcomes such as significantly reduced survival time, especially in patients with severe pulmonary disease. Areas covered: Pubmed was searched using the following keywords: Calprotectin + COVID19, S100A8/ A9 + COVID19, S100A8 + COVID-19, S100A9 + COVID-19, MRP8/14 + COVID19; L1 + COVID-19 between May 2020 and 8 March 2021. The results summarized in this review provide supporting evidence and propose future directions that define calprotectin as an important biomarker in COVID-19. Expert opinion: Calprotectin represents a promising serological biomarker for the risk assessment of COVID-19 patients.

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Anakinra as a potential alternative in the treatment of severe acute respiratory infection associated with SARS-CoV-2 refractory to tocilizumab

Cited by 10 publications

References 7 publications

Tocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis

Tocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis

The Role of Cytokines and Chemokines in Severe Acute Respiratory Syndrome Coronavirus 2 Infections

Circulating Calprotectin as a Biomarker of COVID-19 Severity

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