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Current evidence on the use of anakinra in COVID-19.

ABSTRACT: Despite the progressing knowledge in COVID-19 management, remdesivir is the only agent that got approval to inhibit viral replication. However, there are limited data about effective immunomodulatory agents to prevent cytokine release in COVID-19. Cytokine release syndrome in COVID-19 resembles secondary hemophagocytic lymphohistiocytosis, in which interleukin-1 (IL-1) plays a key role. Anakinra is the first recombinant IL-1 receptor antagonist studied for off-label use in COVID-19 treatment. This study reviews the current clinical evidence on the role of interleukin-1 in COVID-19-related cytokine storm, therapeutic effects, significant clinical concerns, and pros and cons of anakinra administration in the management of COVID-19 patients. In this review, four items are shown to be important for achieving the optimal therapeutic effects of anakinra in COVID-19 patients. These items include duration of treatment ≥ 10 days, doses ≥ 100 mg, intravenous administration, and early initiation of therapy. Also, anakinra might be more beneficial in the early stages of the disease when higher levels of cytokines are yet to be observed, which could prevent progression to severe illness and mechanical ventilation. Further studies are required to address the SARS-CoV-2 induced cytokine release syndrome and the role of anakinra in identifying ideal treatment approaches for COVID-19 patients based on their clinical status.

SUBMITTER: Khani E

PROVIDER: S-EPMC9296834 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Current evidence on the use of anakinra in COVID-19.

Khani Elnaz E Shahrabi Marzieh M Rezaei Haleh H Pourkarim Fariba F Afsharirad Hoda H Solduzian Mohammad M

International immunopharmacology 20220720

Despite the progressing knowledge in COVID-19 management, remdesivir is the only agent that got approval to inhibit viral replication. However, there are limited data about effective immunomodulatory agents to prevent cytokine release in COVID-19. Cytokine release syndrome in COVID-19 resembles secondary hemophagocytic lymphohistiocytosis, in which interleukin-1 (IL-1) plays a key role. Anakinra is the first recombinant IL-1 receptor antagonist studied for off-label use in COVID-19 treatment. Th ...[more]

PMID: 35905562

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Project description:ObjectiveTo report the clinical experience with anakinra in preventing mechanical ventilation in patients with coronavirus disease 2019 (COVID-19), symptoms of cytokine storm syndrome, and acute hypoxemic respiratory failure.MethodsTo be included in this retrospective case series, patients must have had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), fever, ferritin levels >1,000 ng/ml with 1 additional laboratory marker of hyperinflammation, and acute hypoxemic respiratory failure. Acute hypoxemic respiratory failure was defined as requiring 15 liters of supplemental oxygen via a nonrebreather mask combined with 6-liter nasal cannula or use of ≥95% oxygen by high-flow nasal cannula. We excluded patients in whom there was suspicion of bacterial infection or who were receiving immunosuppressants. Subcutaneous anakinra was initiated at 100 mg every 6 hours and gradually tapered off completely. The primary outcome was the prevention of mechanical ventilation.ResultsOf the 14 patients who met the criteria, 11 patients received anakinra for a maximum of 19 days. Seven of the patients who started anakinra treatment ≤36 hours after onset of acute hypoxemic respiratory failure did not require mechanical ventilation, and all were discharged home. Four patients who started anakinra ≥4 days after onset of acute hypoxemic respiratory failure required mechanical ventilation. Of those, 3 patients were extubated (2 discharged home and 1 remained hospitalized), and 1 died. All 3 patients who met the criteria but did not receive anakinra required mechanical ventilation. Two patients were extubated (1 discharged home and 1 remained hospitalized), and 1 remained on mechanical ventilation.ConclusionOur data suggest that anakinra could be beneficial in treating COVID-19 patients with evidence of cytokine storm syndrome when initiated early after onset of acute hypoxemic respiratory failure. Our patient selection and treatment approach should be considered for investigation in a clinical trial to determine the safety and efficacy of anakinra in treating patients with COVID-19 and symptoms of cytokine storm syndrome.

Project description:Background and objectives A flare-up in coronavirus disease 2019 (COVID-19) cases threatens the health of people, and though there is no proven pharmacological treatment, many analytical studies have suggested that interleukin-6 (IL-6) levels are elevated in cases of severe COVID-19 and that the anti-IL-6 biologic agent tocilizumab may be beneficial. This is a critical review of studies aiming to assess the safety and efficacy of tocilizumab as compared to the standard regimen in patients with COVID-19. Materials and methods Online databases (PubMed and Cochrane) were searched until June 29, 2020, for original articles investigating the immunological response in COVID-19 and its treatment with tocilizumab. Data on multiple baseline characteristics and pre-specified endpoints were extracted and pooled using a random effect model. We used Review Manager version 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, 2014, Denmark) and Stata 11.0 (Stata Corporation LP, College Station, TX) for all analyses. Risk ratios (RR) and the weighted mean difference (WMD) with the corresponding 95% confidence interval (CI) were calculated. Results From a total of 1,246 identified articles, 13 studies were included after duplicate removal and narrowing based on title and abstract. Of the 13 included studies, seven case-control studies were shortlisted for meta-analysis (quantitative) and six-single arm studies were used in the discussion (qualitative). These studies had 766 patients (351 in the tocilizumab arm and 414 in the control arm). Their pooled analysis demonstrated that mortality was significantly lower in the tocilizumab group (RR=0.56 [0.34, 0.92]; p=0.02; I2=76%), as was the need for artificial invasive ventilation (RR=0.34 [0.12, 0.99]; p=0.05; I2=0%) as compared to the control group. No significant differences were observed between tocilizumab and control group in intensive care unit admissions (RR=0.73 [0.15, 3.59]; p=0.70; I2=60%) and risks of post-drug infection (RR=1.29 [0.41, 4.04]; p=0.66; I2=88%). In terms of efficacy outcome, improved oxygen saturation (RR=1.13 [1.04, 1.65]; p=0.02; I2=0%) was reported to be markedly significant in tocilizumab patients when compared with the standard care group. Conclusions Our results based on pooled studies show tocilizumab to be safe and efficacious in reducing mortality among critically ill COVID-19 patients. However, due to the limited number of observational studies, the positive findings should be viewed cautiously and warrant further investigation.

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Current evidence on the use of anakinra in COVID-19.

Publications

Current evidence on the use of anakinra in COVID-19.

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