4.7 Article

The janus-kinase inhibitor ruxolitinib in SARS-CoV-2 induced acute respiratory distress syndrome (ARDS)

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LEUKEMIA
卷 35, 期 10, 页码 2917-2923

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SPRINGERNATURE
DOI: 10.1038/s41375-021-01374-3

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资金

  1. Novartis
  2. German Jose Carreras Leukemia foundation [AH 06-01]
  3. European Union under the program Europaischer Fonds fur regionale Entwicklung - Investition in Ihre Zukunft
  4. Universities Giessen and Marburg Lung Center (UGMLC)
  5. German Center for Lung Research (DZL)
  6. University Hospital Giessen and Marburg (UKGM)
  7. Deutsche Forschungsgemeinschaft [SFB 1021, KFO 309, SK 317/1-1, 428518790]
  8. Foundation for Pathobiochemistry and Molecular Diagnostics

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The study showed that the use of ruxolitinib in ARDS patients induced by COVID-19 may be feasible and effective. Early initiation of ruxolitinib was associated with better outcomes.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 (coronavirus disease 2019), which is associated with high morbidity and mortality, especially in elder patients. Acute respiratory distress syndrome (ARDS) is a life-threatening complication of COVID-19 and has been linked with severe hyperinflammation. Dexamethasone has emerged as standard of care for COVID-19 associated respiratory failure. In a non-randomized prospective phase II multi-center study, we asked whether targeted inhibition of Janus kinase-mediated cytokine signaling using ruxolitinib is feasible and efficacious in SARS-CoV-2- induced ARDS with hyperinflammation. Sixteen SARS-CoV-2 infected patients requiring invasive mechanical ventilation for ARDS were treated with ruxolitinib in addition to standard treatment. Ruxolitinib treatment was well tolerated and 13 patients survived at least the first 28 days on treatment, which was the primary endpoint of the trial. Immediate start of ruxolitinib after deterioration was associated with improved outcome, as was a lymphocyte-to-neutrophils ratio above 0.07. Together, treatment with the janus-kinase inhibitor ruxolitinib is feasible and might be efficacious in COVID-19 induced ARDS patients requiring invasive mechanical ventilation. The trial has been registered under EudraCT-No.: 2020-001732-10 and NCT04359290.

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