Pharmacology and Adverse Events of Emergency-Use Authorized Medication in Moderate to Severe COVID-19 DOI Creative Commons
Jen‐Yu Hsu, Yan–Chiao Mao, Po‐Yu Liu

и другие.

Pharmaceuticals, Год журнала: 2021, Номер 14(10), С. 955 - 955

Опубликована: Сен. 23, 2021

Some effective drugs have been approved or issued an Emergency Use Authorization for the treatment of COVID-19 in hospitalized patients, but post-market surveillance is warranted to monitor adverse events. We reviewed clinical trials and case reports patients with moderate-to-severe infection who received remdesivir, baricitinib, tocilizumab, sarilumab. The drug-specific pharmacokinetics, toxicity, drug interactions are summarized this study. Remdesivir baricitinib small-molecule that mainly metabolized by kidneys, while tocilizumab sarilumab monoclonal antibody metabolic pathways currently not fully understood. most common events these alterations liver function, serious rarely attributed them. Only a few studies reported remdesivir might be cardiotoxic cause thromboembolism. Biological agents such as could inhibit pathway inflammatory processes, leading immune dysregulation, so risk secondary should assessed before prescribing. Further recognition pathogenic mechanism factors essential optimizing strategies.

Язык: Английский

Interleukin-6 cytokine: An overview of the immune regulation, immune dysregulation, and therapeutic approach DOI Open Access
Mansur Aliyu, Fatema Tuz Zohora, Abubakar Umar Anka

и другие.

International Immunopharmacology, Год журнала: 2022, Номер 111, С. 109130 - 109130

Опубликована: Авг. 12, 2022

Язык: Английский

Процитировано

184
ESCMID COVID-19 living guidelines: drug treatment and clinical management DOI Creative Commons
Michele Bartoletti, Özlem Kurt Azap, Aleksandra Barać

и другие.

Clinical Microbiology and Infection, Год журнала: 2021, Номер 28(2), С. 222 - 238

Опубликована: Ноя. 22, 2021

Язык: Английский

Процитировано

143
Effect of anti-interleukin drugs in patients with COVID-19 and signs of cytokine release syndrome (COV-AID): a factorial, randomised, controlled trial DOI Creative Commons
Jozefien Declercq, Karel Van Damme, Elisabeth De Leeuw

и другие.

The Lancet Respiratory Medicine, Год журнала: 2021, Номер 9(12), С. 1427 - 1438

Опубликована: Окт. 29, 2021

SummaryBackgroundInfections with SARS-CoV-2 continue to cause significant morbidity and mortality. Interleukin (IL)-1 IL-6 blockade have been proposed as therapeutic strategies in COVID-19, but study outcomes conflicting. We sought whether of the or IL-1 pathway shortened time clinical improvement patients hypoxic respiratory failure, signs systemic cytokine release syndrome.MethodsWe did a prospective, multicentre, open-label, randomised, controlled trial, hospitalised hypoxia, syndrome across 16 hospitals Belgium. Eligible had proven diagnosis COVID-19 symptoms between 6 days, ratio partial pressure oxygen fraction inspired (PaO2:FiO2) less than 350 mm Hg on room air 280 supplemental oxygen, their serum (either single ferritin measurement more 2000 μg/L immediately requiring high flow mechanical ventilation, concentration 1000 μg/L, which increasing over previous 24 h, lymphopenia below 800/mL two following criteria: an 700 lactate dehydrogenase 300 international units per L, C-reactive protein 70 mg/L, D-dimers ng/mL). The COV-AID trial has 2 × factorial design evaluate versus no blockade. Patients were randomly assigned by means permuted block randomisation varying size stratification centre. In first randomisation, receive subcutaneous anakinra once daily (100 mg) for 28 days until discharge, (1:2). second step, allocated dose siltuximab (11 mg/kg) intravenously, tocilizumab (8 (1:1:1). primary outcome was improvement, defined from increase at least points 6-category ordinal scale discharge hospital alive. supportive efficacy endpoints assessed intention-to-treat population. Safety safety This is registered online ClinicalTrials.gov (NCT04330638) EudraCT (2020-001500-41) complete.FindingsBetween April 4, Dec 6, 2020, 342 (n=112) (n=230) simultaneously (n=227; 114 113 siltuximab) (n=115). Most male (265 [77%] 342), median age 65 years (IQR 54–73), Systematic Organ Failure Assessment (SOFA) score 3 (2–4). All included analysis. estimated 12 (95% CI 10–16) group (10–15) (hazard [HR] 0·94 [95% 0·73–1·21]). For group, 11 (11–16) (HR 1·00 [0·78–1·29]). 55 died during study, evidence differences mortality treatment groups found. incidence serious adverse events infections similar groups.InterpretationDrugs targeting not shorten this sample low SOFA score, baseline risk.FundingBelgian Health Care Knowledge Center VIB Grand Challenges program.

Язык: Английский

Процитировано

71
Immunotherapy of COVID-19: Inside and Beyond IL-6 Signalling DOI Creative Commons
Gaetano Zizzo, Antonio Tamburello, Laura Castelnovo

и другие.

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Фев. 22, 2022

Acting on the cytokine cascade is key to preventing disease progression and death in hospitalised patients with COVID-19. Among anti-cytokine therapies, interleukin (IL)-6 inhibitors have been most used studied since beginning of pandemic. Going through previous observational studies, subsequent randomised controlled trials, meta-analyses, we focused baseline characteristics recruited, identifying favourable features light positive or negative study outcomes; taking into account biological significance predictivity IL-6 other biomarkers according specific thresholds, ultimately attempted delineate precise windows for therapeutic intervention. By stimulating scavenger macrophages T-cell responsivity, seems protective against viral replication during asymptomatic infection; still early tissue damage by modulating release granzymes lymphokines mild-moderate disease; importantly pathogenic severe inducing proinflammatory activation immune endothelial cells (through trans-signalling trans-presentation); again critical exerting homeostatic roles repair cis-signalling), while IL-1 drives hyperinflammation. inhibitors, particularly anti-IL-6R monoclonal antibodies (e.g., tocilizumab, sarilumab), are effective disease, characterised concentrations ranging from 35 90 ng/mL (reached circulation within 6 days hospital admission), a ratio partial pressure arterial oxygen (PaO2) fraction inspired (FiO2) between 100 200 mmHg, requirement high-flow non-invasive ventilation, C-reactive protein levels 120 160 mg/L, ferritin 800 1600 ng/mL, D-dimer 750 3000 lactate dehydrogenase 350 500 U/L. Granulocyte-macrophage colony-stimulating factor might similar opportunity but different age preferences compared (over under 70 years old, respectively). Janus kinase baricitinib) may also be moderate whereas anakinra) disease. Correct use biologics based essential successful outcomes could inform future new trials more appropriate recruiting criteria.

Язык: Английский

Процитировано

60
STAT3 Signaling in Breast Cancer: Multicellular Actions and Therapeutic Potential DOI Open Access
Sarah Q. To, Rhynelle S. Dmello,

Anna K. Richards

и другие.

Cancers, Год журнала: 2022, Номер 14(2), С. 429 - 429

Опубликована: Янв. 15, 2022

Interleukin (IL)-6 family cytokines, such as IL-6 and IL-11, are defined by the shared use of gp130 receptor for downstream activation STAT3 signaling genes which contribute to "hallmarks cancer", including proliferation, survival, invasion metastasis. Increased expression these or ligand-specific receptors IL-6R IL-11RA, in breast tumors positively correlate disease progression poorer patient outcome. In this review, we examine evidence from pre-clinical studies that enhanced IL-11 mediated gp130/STAT3 cancer. Key processes cytokines heterogeneous nature cancer, immune evasion metastatic potential, discussed. We latest research into therapeutic targeting inhibit transcriptional activity a potential cancer treatment, current clinical trials. The importance cellular promote development warrants further understanding molecular basis its actions help guide future targets.

Язык: Английский

Процитировано

56
Interleukin-6 blocking agents for treating COVID-19: a living systematic review DOI
Lina Ghosn,

Rouba Assi,

Theodoros Evrenoglou

и другие.

Cochrane library, Год журнала: 2023, Номер 2023(6)

Опубликована: Июнь 1, 2023

Язык: Английский

Процитировано

39
Effect of tocilizumab, sarilumab, and baricitinib on mortality among patients hospitalized for COVID-19 treated with corticosteroids: a systematic review and meta-analysis DOI Creative Commons
Arthur M. Albuquerque, Igor Eckert, Lucas Tramujas

и другие.

Clinical Microbiology and Infection, Год журнала: 2022, Номер 29(1), С. 13 - 21

Опубликована: Июль 19, 2022

Язык: Английский

Процитировано

37
Beneficial and harmful outcomes of tocilizumab in severe COVID‐19: A systematic review and meta‐analysis DOI Open Access
Manuel Rubio‐Rivas, Carlos G. Forero, José María Mora‐Luján

и другие.

Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy, Год журнала: 2021, Номер 41(11), С. 884 - 906

Опубликована: Сен. 24, 2021

The results of studies tocilizumab (TCZ) in COVID-19 are contradictory. Our study aims to update medical evidence from controlled observational and randomized clinical trials (RCTs) on the use TCZ hospitalized patients with COVID-19.

Язык: Английский

Процитировано

36
Cancer-associated fibroblast-like fibroblasts in vocal fold leukoplakia suppress CD8+T cell functions by inducing IL-6 autocrine loop and interacting with Th17 cells DOI
Yi Fang, Min Chen, Guangfei Li

и другие.

Cancer Letters, Год журнала: 2022, Номер 546, С. 215839 - 215839

Опубликована: Авг. 10, 2022

Язык: Английский

Процитировано

29
Cardiac Involvement in Patients With Multisystem Inflammatory Syndrome in Adults DOI Creative Commons
Giulia La Vecchia, Marco Giuseppe Del Buono, Aldo Bonaventura

и другие.

Journal of the American Heart Association, Год журнала: 2024, Номер 13(4)

Опубликована: Фев. 13, 2024

Multisystemic inflammatory syndrome in adults is a hyperinflammatory condition following (within 4-12 weeks) SARS-CoV-2 infection. Here, the dysregulation of immune system leads to multiorgan involvement often affecting heart. Cardiac multisystemic has been described mainly young men without other comorbidities and may present with different clinical scenarios, including acute heart failure, life-threatening arrhythmias, pericarditis, myocarditis, nonnegligible risk mortality (up 7% all cases). The heterogeneity its features absence clear case definition make differential diagnosis postinfectious (eg, infective myocarditis) diseases adult Still disease macrophage activation syndrome) challenging. Moreover, evidence on efficacy specific treatments targeting response underlying this glucocorticoids, immunoglobulins, immunomodulatory agents) sparse not supported by randomized trials. In review article, we aim provide an overview diagnostic workup cardiac involvement, highlighting possible pathogenetic mechanisms therapeutic management, along remaining knowledge gaps field.

Язык: Английский

Процитировано

6