scholarly journals Efficacy of tocilizumab in COVID-19: A review of the current evidence

2021 ◽  
Vol 104 (3) ◽  
pp. 003685042110303
Author(s):  
Walid Alam ◽  
Abdul Rahman Bizri
Keyword(s):  
Randomized Clinical Trials ◽  
Current Evidence ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Inflammatory Reactions ◽  
Health Measures ◽  
Clinical Trial Registries ◽  
Overwhelming Evidence ◽  
Clinical Benefits ◽  
Mixed Efficacy

As cases of coronavirus 2019 (COVID-19) keep rising, reported deaths are increasing. Public health measures have been implemented with mixed efficacy. As vaccines are becoming more widely available and accessible globally, treating critically ill COVID-19 patients remains an issue with only dexamethasone found to be therapeutically effective to date. However, trials studying the efficacy of IL-6 inhibitors, namely tocilizumab have been underway with promising results. This paper is a narrative review that aims to review the current evidence provided by randomized clinical trials (RCT) for the use of tocilizumab in COVID-19. Electronic database searches were carried out in Medline, PubMed, Embase, Google Scholar, and ongoing clinical trial registries with the period set from January 1, 2020 to February 20, 2021. Prepublication manuscripts were found using the pre-print repository medRxiv. Keywords included “COVID-19,”“coronavirus,”“SARS-CoV-2,”“sepsis,”“pneumonia,”“cytokine storm,”“cytokine release syndrome,”“IL-6 inhibitors,” and “tocilizumab,” as exact phrases, and a combination of subject headings according to databases syntax. Only trials with a clear and well-defined methodology, at least 100 patients recruited, and which have had results published either after peer review or in pre-print were included. In hospitalized patients with severe COVID-19, who are hypoxic and have a CRP ≥ 75 mg/L, the current evidence favors the use of a combination of tocilizumab and corticosteroids to reduce mortality, among other clinical benefits. There is also overwhelming evidence of the good safety profile of tocilizumab with only few cases of neutropenia reported with a decrease in infection rates. Tocilizumab is currently thought to work through the inhibition of IL-6 receptors (IL-6R), preventing downstream activation of pro-inflammatory reactions and cytokine release syndrome.

scholarly journals Laboratory parameters predicting mortality of adult in-patients with COVID-19 associated cytokine release syndrome treated with high-dose tocilizumab

2021 ◽  
Author(s):  
Botond Lakatos ◽  
Balint Gergely Szabo ◽  
Ilona Bobek ◽  
Laszlo Gopcsa ◽  
Gabriella Beko ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Absolute Lymphocyte Count ◽  
Biochemical Parameter ◽  
High Dose ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Laboratory Parameters ◽  
Proven Efficacy ◽  
Observational Cohort ◽  
Intensive Care Unit Admittance

AbstractLarge randomized clinical trials in severe Coronavirus Disease 2019 (COVID-19) patients have proven efficacy of intravenous tocilizumab. Our aim was to describe the laboratory parameters predicting in-hospital mortality of patients with tocilizumab administration in COVID-19 associated cytokine release syndrome (CRS).We evaluated high-dose (8 mg/kg) intravenous tocilizumab administration in severe and critically ill COVID-19 adult patients fulfilling predefined strict CRS criteria. A single-centre, prospective, observational cohort study was carried out among consecutive adult (≥18 years of age) in-patients with COVID-19 between April 1 and December 31, 2020. The primary endpoint was 28-day all-cause mortality. The changes in laboratory parameters from baseline on day 7 and 14 after administration of tocilizumab were analysed.In total, 1801 patients were admitted to our centre during the study period. One hundred and six patients received tocilizumab, and among them 62 (58.5%) required intensive care unit admittance while 25 (23.6%) deceased. At day 7 after tocilizumab administration, inflammatory markers (CRP, IL-6, ferritin) and lactate dehydrogenase (LDH) values were significantly lower among survivors. Subsequently, at day 14, differences of IL-6 and LDH levels has become more pronounced between subgroups. Restoration of absolute lymphocyte count (ALC) by day 7 and 14 was insufficient among patients who died.In our cohort, administration of high-dose tocilizumab for COVID-19 patients with CRS demonstrated clinical and sustained biochemical parameter improvement in 76.4%. In this patient population high and increasing LDH, IL-6, and low ALC levels had a predictive role for mortality.

scholarly journals Anti-IL-6 versus Anti-IL-6R Blocking Antibodies to Treat Acute Ebola Infection in BALB/c Mice: Potential Implications for Treating Cytokine Release Syndrome

2020 ◽  
Author(s):  
Reid Rubsamen ◽  
Scott Burkholz ◽  
Christopher Massey ◽  
Trevor Brasel ◽  
Tom Hodge ◽  
...  
Keyword(s):  
Host Response ◽  
Viral Infections ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Important Mediator ◽  
Acute Viral Infection ◽  
Clinical Benefits ◽  
Coronavirus Infection ◽  
Blocking Antibodies

ABSTRACTCytokine release syndrome (CRS) is known to be a factor in morbidity and mortality associated with acute viral infections including those caused by filoviruses and coronaviruses. IL-6 has been implicated as a cytokine negatively associated with survival after filovirus and coronavirus infection. However, IL-6 has also been shown to be an important mediator of innate immunity and important for the host response to an acute viral infection. Clinical studies are now being conducted by various researchers to evaluate the possible role of IL-6 blockers to improve outcomes in critically ill patients with CRS. Most of these studies involve the use of anti-IL-6R monoclonal antibodies (α-IL-6R mAbs). We present data showing that direct neutralization of IL-6 with an α-IL-6 mAb in a BALB/c Ebolavirus (EBOV) challenge model produced a statistically significant improvement in outcome compared with controls when administered within the first 24 hours of challenge and repeated every 72 hours. A similar effect was seen in mice treated with the same dose of α-IL-6R mAb when the treatment was delayed 48 hrs post-challenge. These data suggest that direct neutralization of IL-6, early during the course of infection, may provide additional clinical benefits to IL-6 receptor blockade alone during treatment of patients with virus-induced CRS.

scholarly journals Treatment of Severe COVID-19 with Tocilizumab Mitigates Cytokine Storm and Averts Mechanical Ventilation during Acute Respiratory Distress: A Case Report and Literature Review

2020 ◽  
Vol 5 (3) ◽  
pp. 112 ◽  
Author(s):  
Faryal Farooqi ◽  
Naveen Dhawan ◽  
Richard Morgan ◽  
John Dinh ◽  
Kester Nedd ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Respiratory Distress ◽  
Acute Phase ◽  
Current Evidence ◽  
Cytokine Storm ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Acute Phase Reactants ◽  
Standard Drug ◽  
Therapeutic Benefits

COVID-19, caused by the novel severe acute respiratory coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, in 2019 and has resulted in the current pandemic. The disease continues to pose a major therapeutic challenge. Patient mortality is ultimately caused by acute respiratory distress syndrome (ARDS). Cytokine release syndrome (or “cytokine storm”) is likely to be a contributing factor to ARDS in many patients. Because interleukin 6 (IL-6) is known to play a key role in inflammation, IL-6 receptor inhibitors such as tocilizumab may potentially treat COVID-19 by attenuating cytokine release. We present the case of a 48-year-old male with severe COVID-19, on the verge of meeting intubation requirements, who needed progressive oxygen support for respiratory distress. The patient was treated with a non-weight-based dosage of tocilizumab to prevent the onset of a cytokine storm. We chose to administer an IL-6 inhibitor because of the gradually increasing levels of acute phase reactants identified on serial blood draws, as well as his declining respiratory status. The treatment was well-tolerated in conjunction with standard drug therapies for COVID-19 (hydroxychloroquine, azithromycin, and zinc). The patient subsequently experienced marked improvements in his respiratory symptoms and overall clinical status over the following days. We believe that tocilizumab played a substantial role in his ability to avert clinical decline, particularly the need for mechanical ventilation. Ultimately, the patient was downgraded from the ICU and discharged within days. We highlight the potential of IL-6 inhibitors to prevent the progression of respiratory disease to a point requiring ventilator support. This case underscores the potential importance of early serial measurements of IL-6 and cytokine storm-associated acute phase reactants, such as ferritin, D-dimer, and C-reactive protein, in guiding clinical decision-making in the management of patients with suspected COVID-19. Conclusion: The early, proactive identification of serum acute phase reactants should be implemented in the treatment of COVID-19 in order to screen for a primary contributor to mortality—the cytokine storm. This screening, when followed by aggressive early treatment for cytokine storm, may have optimal therapeutic benefits and obviate the need for mechanical ventilation, thereby decreasing mortality. Additionally, we review current evidence regarding cytokine release syndrome in COVID-19 and the use of IL-6 receptor inhibition as a therapeutic strategy, and examine other reported cases in the literature describing IL-6 antagonist treatment for patients with COVID-19.

scholarly journals Description and Analysis of Cytokine Storm in Registered COVID-19 Clinical Trials: A Systematic Review

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 692
Author(s):  
Khalid Eljaaly ◽  
Husam Malibary ◽  
Shaimaa Alsulami ◽  
Muradi Albanji ◽  
Mazen Badawi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
High Variability ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Inflammatory Biomarker ◽  
Clinical Trial Registries ◽  
Cutoff Values ◽  
Definition Of ◽  
D Dimer

The purpose of this systematic review was to describe the characteristics of clinical trials that focused on COVID-19 patients with cytokine release syndrome (CRS) and the variability in CRS definitions. Two authors independently searched three clinical trial registries and included interventional clinical trials on COVID-19 hospitalized patients that required at least one elevated inflammatory biomarker. Relevant data, including the type and cutoff of the measured biomarker, oxygen/respiratory criteria, fever, radiologic criteria, and medications, were summarized. A total of 47 clinical trials were included. The included studies considered the following criteria: oxygen/respiratory criteria in 42 trials (89%), radiologic criteria in 29 trials (62%), and fever in 6 trials (18%). Serum ferritin was measured in 35 trials (74%), CRP in 34 trials (72%), D-dimer in 26 trials (55%), LDH in 24 trials (51%), lymphocyte count in 14 trials (30%), and IL-6 in 8 trials (17%). The cutoff values were variable for the included biomarkers. The most commonly used medications were tocilizumab, in 15 trials (32%), and anakinra in 10 trials (24.4%). This systematic review found high variability in CRS definitions and associated biomarker cutoff values in COVID-19 clinical trials. We call for a standardized definition of CRS, especially in COVID-19 patients.

Resveratrol Supplementation in Patients with Non-Alcoholic Fatty Liver Disease: Systematic Review and Meta-analysis

2017 ◽  
Vol 26 (1) ◽  
pp. 59-67 ◽  
Author(s):  
Ahmed Elgebaly ◽  
Ibrahim A. I. Radwan ◽  
Mohamed M. AboElnas ◽  
Hamza H. Ibrahim ◽  
Moutaz F. M. Eltoomy ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Randomized Clinical Trials ◽  
Controlled Trial ◽  
Antioxidant Properties ◽  
Density Lipoprotein ◽  
Current Evidence ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Background: Resveratrol is a potential treatment option for management of non-alcoholic fatty liver disease (NAFLD) due to its anti-inflammatory, antioxidant properties, and calorie restriction-like effects. We aimed to synthesise evidence from published randomized clinical trials (RCTs) about the efficacy of resveratrol in the management of NAFLD.Methods: A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central was conducted using relevant keywords. Records were screened for eligible studies and data were extracted and synthesized using Review Manager Version 5.3 for windows. Subgroup analysis and sensitivity analysis were conducted.Results: Four RCTs (n=158 patients) were included in the final analysis. The overall effect estimates did not favor resveratrol group in terms of: serum ALT (MD -2.89, 95%CI [-15.66, 9.88], p=0.66), serum AST (MD -3.59, 95%CI [-13.82, 6.63], p=0.49), weight (MD -0.18, 95%CI [-0.92, 0.55], p=0.63), BMI (MD -0.10, 95 %CI [-0.43, 0.24], p=0.57), blood glucose level (MD -0.27, 95%CI [-0.55, 0.01], p=0.05), insulin level (MD -0.12, 95%CI [-0.69, 0.46], p=0.69), triglyceride level (MD 0.04, 95%CI [-0.45, 0.53], p=0.87), and LDL level (MD 0.21, 95%CI [-0.41, 0.83], p=0.51). Pooled studies were heterogeneous.Conclusion: Current evidence is insufficient to support the efficacy of resveratrol in the management of NAFLD. Resveratrol does not attenuate the degree of liver fibrosis or show a significant decrease in any of its parameters.Abbreviations: ALT: Alanine aminotransferase; AMPK: AMP-activated protein kinase; AST: Aspartate aminotransferase; BMI: Body mass index; CK-18: Cytokeratin-18; CRP: C-reactive protein; HC: Head circumference; HDL: High density lipoprotein; IL-6: Interleukin-6; LDL: Low density lipoprotein; MD: Mean difference; NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; RCT: Randomized Controlled Trial; RR: Relative risk; SIRT1: Silent information regulation 2 homologue 1; TNF-α: Tumor necrosis factor α; WC: Waist circumference; WHR: Waist hip ratio.

Sign in / Sign up

Export Citation Format

Share Document