Real-life experience of tocilizumab use in COVID-19 patients

Madenidou, Anastasia-Vasiliki; Bukhari, Marwan

doi:10.1093/rheumatology/keaa325

Cited by 6 publications

(7 citation statements)

References 13 publications

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“…Interestingly, we report that IL-6 levels increased massively in the following days after TCZ administration only in the patients that subsequently deceased, but not in those that remained alive where we observed just a small spike at day 3. Other authors have found a similar trend for IL-6 concentration differences between deceased and discharged patients but with no statistical analysis for between-group comparison (Luo et al, 2020;Madenidou and Bukhari, 2020;Toniati et al, 2020). However, it is unclear whether IL-6 represents a marker and/or mediator of COVID-19 severe progression (Chastain et al, 2020).…”

Section: Discussionmentioning

confidence: 94%

“…Tocilizumab (TCZ) is an IL-6R antagonist that can effectively block the IL-6 signal transduction pathway. In observational studies, administration of TCZ to patients with pneumonia due to SARS-CoV-2 has been associated with higher survival rates ( Gokhale et al, 2020 ; Rodríguez-Baño et al, 2020 ), and/or significant clinical improvement, including laboratory parameters like CRP ( Madenidou and Bukhari, 2020 ; Toniati et al, 2020 ; Xu et al, 2020 ). Moreover, while some clinical trials did report no association of TCZ with clinical improvement ( Roche Group Media Relations., 2020 ; Stone et al, 2020 ; Hermine et al, 2021 ; Salvarani et al, 2021 ; Veiga et al, 2021 ), those with a higher sample size did report a better COVID-19 outcome after TCZ treatment compared to the control group or null hypothesis ( Perrone et al, 2020 ; Abani et al, 2021 ; Salama et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Tocilizumab in COVID-19: Factors Associated With Mortality Before and After Treatment

et al. 2021

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Tocilizumab (TCZ) has been administered in SARS-CoV-2 pneumonia but the factors associated with mortality before and after treatment remain unclear. Cox regression models were used to estimate the predictors of time to death in a cohort of hospitalized patients with COVID-19 receiving TCZ. In addition, the mean differences between discharged and deceased patients in laboratory parameters measured before and 3, 6 and 9 days after TCZ administration were estimated with weighted generalized estimation equations. The variables associated with time to death were immunosuppression (Hazard Ratio-HR 3.15; 95% confidence interval-CI 1.17, 8.51), diabetes mellitus (HR 2.63; 95% CI 1.23–5.64), age (HR 1.05; 95% CI 1.02–1.09), days since diagnosis until TCZ administration (HR 1.05, 95% CI 1.00–1.09), and platelets (HR 0.27; 95% CI: 0.11, 0.69). In the post-TCZ analysis and compared to discharged patients, deceased patients had more lactate dehydrogenase (p = 0.013), troponin I (p = 0.013), C-reactive protein (p = 0.013), neutrophils (p = 0.024), and fewer platelets (p = 0.013) and lymphocytes (p = 0.013) as well as a lower average PaO2/FiO2 ratio. In conclusion, in COVID-19 diagnosed patients receiving TCZ, early treatment decreased the risk of death, while age, some comorbidities and baseline lower platelet counts increased that risk. After TCZ administration, lower platelet levels were again associated with mortality, together with other laboratory parameters.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Tocilizumab in COVID-19: Factors Associated With Mortality Before and After Treatment

et al. 2021

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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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“…Additionally, high-ow oxygen and non-invasive ventilation (22.5%), tracheal intubation (20%), and extracorporeal membrane oxygenation (n = 2) was performed on the patients. The median period from the time of symptom onset to admission into ICU was 20 days (IQR [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29], and the median time of ICU stay was 8.…”

Section: Demographic and Baseline Clinical Characteristics Of Patientmentioning

confidence: 99%

“…Nevertheless, regarding the clinical symptoms of COVID-19, including lung injury and the circulation of various cytokines, the cytokine pro les in patients with COVID-19 were distinct from those of typical cytokine storm including CRS, hemophagocytic lymphohistiocytosis, or macrophage activation syndrome [19,20]. IL-6 antagonists, which have been approved for treating chimeric antigen receptor T cell-induced CRS, have demonstrated various effects on patients with COVID-19 in multiple studies [21]. It is di cult to draw conclusions because of the variable participants and intervention criteria.…”

Section: Il-6 Il-8 and Il-10 Are Associated With The Survival Of Pamentioning

confidence: 99%

Dynamic changes in serum IL-6, IL-8, and IL-10 are associated with the outcome of patients with severe COVID-19 in ICU

Liu

Cui

et al. 2020

Preprint

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Background: Biomarkers that would help prognosticate outcomes and guide treatment of patients with severe coronavirus disease 2019 (COVID-19) are currently required. We aimed to investigate whether the dynamic variation of cytokines was associated with the survival of patients admitted to an intensive care unit (ICU).Methods: A retrospective study was performed on 40 patients with COVID-19 admitted to an ICU in Wuhan, China. Demographic, clinical, and laboratory variables were collected, and serum cytokines were kinetically assessed. A multivariable- adjusted generalized linear regression model was used to evaluate the differences in serum cytokine levels between survivor and non-survivors.Results: Among the 40 patients included, a significant positive correlation was found between multiple cytokines. Serum levels of IL-6, IL-10, and tumor necrosis factor alpha in non-survivors were consistently elevated compared to that of the survivors. Kinetic variations of IL-6, IL-8, and IL-10 were associated with a fatal outcome in severe patients with COVID-19, independent of sex, age, absolute lymphocyte count, direct bilirubin, hypertension, chronic obstructive pulmonary disease, and cancer.Conclusion: Dynamic changes in serum IL-6, IL-8, and IL-10 levels were associated with survival in ICU and could serve as a predictive biomarker in patients with severe COVID-19 to determine therapeutic options.

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Real-life experience of tocilizumab use in COVID-19 patients

Cited by 6 publications

References 13 publications

Tocilizumab in COVID-19: Factors Associated With Mortality Before and After Treatment

Tocilizumab in COVID-19: Factors Associated With Mortality Before and After Treatment

Circulating Calprotectin as a Biomarker of COVID-19 Severity

Dynamic changes in serum IL-6, IL-8, and IL-10 are associated with the outcome of patients with severe COVID-19 in ICU

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