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Interleukin-6 receptor blockade in patients with COVID-19: placing clinical trials into context.
Angriman, Federico; Ferreyro, Bruno L; Burry, Lisa; Fan, Eddy; Ferguson, Niall D; Husain, Shahid; Keshavjee, Shaf H; Lupia, Enrico; Munshi, Laveena; Renzi, Samuele; Ubaldo, Onion Gerald V; Rochwerg, Bram; Del Sorbo, Lorenzo.
  • Angriman F; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; Department of Critical Care Medicine, Sunnybrook Health Sciences Ce
  • Ferreyro BL; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; Department of Medicine, Division of Respirology, Sinai Health Syste
  • Burry L; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada; Department of Pharmacy and Medicine, Sinai Health System, Toronto, ON, Canada.
  • Fan E; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada;
  • Ferguson ND; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; Department of Medicine, University of Toronto, Toronto, ON, Canada;
  • Husain S; Transplant Infectious Diseases, Ajmera Transplant Center, University Health Network, University of Toronto, Toronto, ON, Canada.
  • Keshavjee SH; Toronto Lung Transplant Program and Division of Thoracic Surgery, Toronto General Hospital, Toronto, ON, Canada.
  • Lupia E; Department of Medical Sciences, University of Turin, Turin, Italy.
  • Munshi L; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada; Department of Medicine, Division of Respirology, Sinai Health Syste
  • Renzi S; The Hospital for Sick Children, Division of Haematology/Oncology, Toronto, ON, Canada.
  • Ubaldo OGV; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Department of Medicine, Division of Respirology, Sinai Health System and University Health Network, Toronto, ON, Canada.
  • Rochwerg B; Department of Medicine, Division of Critical Care, and Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
  • Del Sorbo L; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Department of Medicine, Division of Respirology, Sinai Health System and University Health Network, Toronto, ON, Canada.
Lancet Respir Med ; 9(6): 655-664, 2021 06.
Article in English | MEDLINE | ID: covidwho-1209411
ABSTRACT
The pleiotropic cytokine interleukin-6 (IL-6) has been implicated in the pathogenesis of COVID-19, but uncertainty remains about the potential benefits and harms of targeting IL-6 signalling in patients with the disease. The efficacy and safety of tocilizumab and sarilumab, which block the binding of IL-6 to its receptor, have been tested in adults with COVID-19-related acute respiratory illness in randomised trials, with important differences in trial design, characteristics of included patients, use of co-interventions, and outcome measurement scales. In this Series paper, we review the clinical and methodological heterogeneity of studies of IL-6 receptor antagonists, and consider how this heterogeneity might have influenced reported treatment effects. Timing from clinical presentation to treatment, severity of illness, and concomitant use of corticosteroids are among the factors that might have contributed to apparently inconsistent results. With an understanding of the sources of variability in these trials, available evidence could be applied to guide clinical decision making and to inform the enrichment of future studies.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Clinical Trials as Topic / Receptors, Interleukin-6 / Antibodies, Monoclonal, Humanized / COVID-19 Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Limits: Humans Language: English Journal: Lancet Respir Med Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Clinical Trials as Topic / Receptors, Interleukin-6 / Antibodies, Monoclonal, Humanized / COVID-19 Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Limits: Humans Language: English Journal: Lancet Respir Med Year: 2021 Document Type: Article