Use of the IL‐6R antagonist tocilizumab in hospitalized COVID‐19 patients

Patel, Krish; Gooley, Ted; Bailey, Neil; Bailey, Megumi; Hegerova, Livia; Batchelder, Ami; Holdread, Heather; Dunleavy, Vanessa; Downey, Tyler; Frisvold, Jens; Megrath, Samantha; Pagarigan, Krystle T.; Szeto, Jennie; Rueda, Justin; Islam, Adel; Maree, Cynthia L.; Nyatsatsang, Sonam T.; Bork, Sarah E; Lipke, Anne B.; O’Mahony, D. Shane; Wagner, Teresa; Pulido, Juan N.; Mignone, John L.; Youssef, Samuel; Hartman, Matthew E.; Goldman, Jason D.; Pagel, John M.

doi:10.1111/joim.13163

Cited by 28 publications

(23 citation statements)

References 8 publications

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“…Indeed, clinical trials assessing the benefits of inflammatory cytokine blockade targeting IL-6 and its upstream mediator IL-1ß are in progress [9]. Given the heterogeneous preliminary results so far in trials applying IL-6 blockade in more severe cases of COVID-19 [22,23], the results of the present study may suggest to elucidate the specific role of IL-6 blockade in uncomplicated COVID-19 patients with cardiovascular comorbidities. Likewise, in light of the observed enhanced intravascular coagulation even during the uncomplicated phase of COVID-19 in patients with cardiovascular comorbidities, more aggressive anticoagulation treatment strategies may be warranted in these patients, as suggested in a recent retrospective analysis [24].…”

Section: Discussionmentioning

confidence: 88%

Elevated markers of thrombo-inflammatory activation predict outcome in patients with cardiovascular comorbidities and COVID-19 disease: insights from the LEOSS registry

et al. 2020

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Aims SARS-CoV-2 infection is associated with adverse outcomes in patients with cardiovascular disease. Here, we analyzed whether specific biomarkers predict the clinical course of COVID-19 in patients with cardiovascular comorbidities. Methods and results We enrolled 2147 patients with SARS-CoV-2 infection which were included in the Lean European Open Survey on SARS-CoV‑2 (LEOSS)-registry from March to June 2020. Clinical data and laboratory values were collected and compared between patients with and without cardiovascular comorbidities in different clinical stages of the disease. Predictors for mortality were calculated using multivariate regression analysis. We show that patients with cardiovascular comorbidities display significantly higher markers of myocardial injury and thrombo-inflammatory activation already in the uncomplicated phase of COVID-19. In multivariate analysis, elevated levels of troponin [OR 1.54; (95% CI 1.22–1.96), p < 0.001)], IL-6 [OR 1.69 (95% CI 1.26–2.27), p < 0.013)], and CRP [OR 1.32; (95% CI 1.1–1.58), p < 0.003)] were predictors of mortality in patients with COVID-19. Conclusion Patients with cardiovascular comorbidities show elevated markers of thrombo-inflammatory activation and myocardial injury, which predict mortality, already in the uncomplicated phase of COVID-19. Starting targeted anti-inflammatory therapy and aggressive anticoagulation already in the uncomplicated phase of the disease might improve outcomes after SARS-CoV-2 infection in patients with cardiovascular comorbidities. Graphic abstract Elevated markers of thrombo-inflammatory activation predict outcome in patients with cardiovascular comorbidities and COVID-19 disease: insights from the LEOSS registry

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Section: Discussionmentioning

confidence: 88%

Elevated markers of thrombo-inflammatory activation predict outcome in patients with cardiovascular comorbidities and COVID-19 disease: insights from the LEOSS registry

et al. 2020

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“…All these studies assessed the effect of tocilizumab administration in patients with severe and/or critical COVID-19. Patel et al [ 40 ] reported the clinical outcomes of the two groups of severe and critical COVID-19 patients separately. Therefore, we have considered them as two separate studies.…”

Section: Resultsmentioning

confidence: 99%

Efficacy and safety of Tocilizumab in severe and critical COVID-19: A Systematic Review and Meta-Analysis

Rezaei

Fatemi

Majd

et al. 2021

Expert Review of Clinical Immunology

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Objectives Currently published papers and clinical guidelines regarding the effects of tocilizumab in severe and critical COVID-19 are contradictory. The aim of this meta-analysis was to combine the results of clinical studies of different designs to investigate the efficacy and safety of tocilizumab in severely-to-critically ill COVID-19 patients. Methods A systematic search was performed in PubMed, Embase, CENTRAL, ClinicalTrials.gov, Scopus, and preprint servers up to 26 December 2020. Since a substantial heterogeneity was expected, a random-effects model was applied to calculate the pooled effect size (ES) and 95% confidence interval (CI) for each study outcome. Results Forty-five comparative studies involving 13,189 patients and 28 single-arm studies involving 1,770 patients were analyzed. The risk of mortality (RR of 0.76 [95%CI 0.65 to 0.89], P < 0.01) and intubation (RR of 0.48 [95%CI 0.24 to 0.97], P = 0.04) were lower in tocilizumab patients compared with controls. We did not find any significant difference in secondary infections, length of hospital stay, hospital discharge before day 14, and ICU admission between groups. Conclusion Tocilizumab can improve clinical outcomes and reduce mortality rates in severe to critical COVID-19 patients. Large-scale randomized controlled trials are still required to improve the statistical power of meta-analysis.

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“…Of the 18 non-randomized articles reported the use of IL-6 inhibitor and its comparator for COVID-19, 16 studies using tocilizumab [ [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , 27 ], 1 using sarilumab [ 25 ], and 1 using siltuximab [ 26 ]. The therapeutic interventions, drug dosing, IL-6 markers, and clinical outcomes are presented in Table 2 .…”

Section: Resultsmentioning

confidence: 99%

Interleukin-6 (IL-6) inhibitors as therapeutic agents for coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis

Pinzon¹,

Wijaya²,

Buana³

2021

Journal of Infection and Public Health

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Introduction Preliminary study showed that coronavirus disease 2019 (COVID-19) disrupt body immune system including dysregulation of cytokine interleukin-6 (IL-6). IL-6 inhibitors agents have been used as treatment option for COVID-19, yet their benefit as therapeutic agent remain unclear. Objective We performed a systematic review and meta-analysis to synthesize the available evidence on the potential therapeutic effect of IL-6 inhibitor agents for the treatment of COVID-19. Methods Two authors initially screened and reviewed the relevant studies from available databases. The data extracted will be tabulated and analyzed for the outcomes. The primary outcome was mortality. Secondary outcomes included discharge from hospital, length of stay, and requirement for mechanical ventilation. The quality of each study was assessed using OCEBM ratings. Results We reviewed 18 studies with a total of 3303 subjects. Tocilizumab was the most commonly used in the studies (15 studies). Meta-analysis of included studies revealed significant reduction in mortality with tocilizumab and sarilumab (RR = 0.61, 95% CI 0.49–0,76). Other outcomes including hospital discharge (RR = 1.04, 95% CI 0.86–1.24), length of stay (mean difference –1.96 days, 95% CI –4.24 to 0.33) or requirement for mechanical ventilation (RR = 0.68, 95% CI 0.32–1.45) revealed no differences of IL-6 inhibitor agents compared to controls. Conclusions Available evidences suggests that IL-6 inhibitor agents do reduce the risk of mortality in COVID-19 especially in severe disease. Further well-designed trials are needed for assessing its efficacy and safety for COVID-19

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Use of the IL‐6R antagonist tocilizumab in hospitalized COVID‐19 patients

Cited by 28 publications

References 8 publications

Elevated markers of thrombo-inflammatory activation predict outcome in patients with cardiovascular comorbidities and COVID-19 disease: insights from the LEOSS registry

Elevated markers of thrombo-inflammatory activation predict outcome in patients with cardiovascular comorbidities and COVID-19 disease: insights from the LEOSS registry

Efficacy and safety of Tocilizumab in severe and critical COVID-19: A Systematic Review and Meta-Analysis

Interleukin-6 (IL-6) inhibitors as therapeutic agents for coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis

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