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dc.contributor.authorKumar, Princy N
dc.contributor.authorHernández-Sánchez, Jules
dc.contributor.authorNagel, Sandra
dc.contributor.authorFeng, Yuning
dc.contributor.authorCai, Fang
dc.contributor.authorRabin, Joseph
dc.contributor.authorMorse, Caryn G
dc.contributor.authorNadig, Nandita R
dc.contributor.authorAshraf, Obaid
dc.contributor.authorGotur, Deepa B
dc.contributor.authorMcComsey, Grace A
dc.contributor.authorGafoor, Khalid
dc.contributor.authorPerin, Patrick
dc.contributor.authorThornton, Sarah C
dc.contributor.authorStubbings, William
dc.contributor.authorLin, Celia J F
dc.contributor.authorTsai, Larry
dc.date.accessioned2022-01-19T13:44:46Z
dc.date.available2022-01-19T13:44:46Z
dc.date.issued2021-12-04
dc.identifier.urihttp://hdl.handle.net/10713/17539
dc.description.abstractBackground: Tocilizumab, an interleukin 6 receptor (IL-6R) antagonist monoclonal antibody, has shown efficacy in patients with coronavirus disease 2019 (COVID-19) pneumonia, but the optimal dose is unknown. Methods: Patients hospitalized for moderate to severe COVID-19 pneumonia were randomized 1:1 to receive standard of care treatment and 1-2 doses of intravenous tocilizumab 4 mg/kg or 8 mg/kg (open-label). Primary pharmacokinetic and pharmacodynamic end points were serum concentrations of tocilizumab and soluble interleukin 6 receptor (sIL-6R), IL-6, ferritin, and C-reactive protein (CRP), from baseline to day 60. The secondary end point was safety. Key exploratory efficacy end points included clinical status, time to discharge, mortality rate, and incidence of mechanical ventilation. Results: Of 100 patients randomized, 49 received tocilizumab 4 mg/kg and 48 received 8 mg/kg. In pharmacokinetic and sIL-6R assessments, dose-dependent differences were seen in patients who received 1 or 2 doses of 4 or 8 mg/kg. Serum concentrations of IL-6, ferritin, and CRP and safety outcomes were comparable between groups. Through day 60, serious adverse events were reported in 30.6% and 25.0% of patients in the 4- and 8-mg/kg groups, respectively. Eight patients (16.3%) in the 4-mg/kg group and 6 (12.5%) in the 8-mg/kg group died. Exploratory time-to-event outcomes favored 8 mg/kg within the first 2 weeks. Conclusions: In patients with moderate to severe COVID-19 pneumonia who received tocilizumab 4 or 8 mg/kg, pharmacokinetic and sIL-6R assessments showed expected dose-dependent effects; pharmacodynamic assessments and safety were comparable, with no new safety signals. Further study is required before a lower dose of tocilizumab can be recommended in patients with COVID-19 pneumonia. Clinical trials registration: NCT04363736.en_US
dc.description.urihttps://doi.org/10.1093/ofid/ofab608en_US
dc.description.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/35024375/en_US
dc.language.isoenen_US
dc.publisherOxford University Pressen_US
dc.relation.ispartofOpen Forum Infectious Diseasesen_US
dc.rights© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.en_US
dc.subjectCOVID-19en_US
dc.subjectpharmacodynamicsen_US
dc.subjectpharmacokineticsen_US
dc.subjectsafetyen_US
dc.subjecttocilizumaben_US
dc.titleSafety and Efficacy of Tocilizumab 4 or 8 mg/kg in Hospitalized Patients With Moderate to Severe Coronavirus Disease 2019 Pneumonia: A Randomized Clinical Trial.en_US
dc.typeArticleen_US
dc.identifier.doi10.1093/ofid/ofab608
dc.identifier.pmid35024375
dc.source.journaltitleOpen forum infectious diseases
dc.source.volume9
dc.source.issue1
dc.source.beginpageofab608
dc.source.endpage
dc.source.countryUnited States


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