The Janus kinase 1/2 inhibitor ruxolitinib in COVID-19 with severe systemic hyperinflammation

Leukemia. 2020 Jul;34(7):1805-1815. doi: 10.1038/s41375-020-0891-0. Epub 2020 Jun 9.

Abstract

A subgroup of patients with severe COVID-19 suffers from progression to acute respiratory distress syndrome and multiorgan failure. These patients present with progressive hyperinflammation governed by proinflammatory cytokines. An interdisciplinary COVID-19 work flow was established to detect patients with imminent or full blown hyperinflammation. Using a newly developed COVID-19 Inflammation Score (CIS), patients were prospectively stratified for targeted inhibition of cytokine signalling by the Janus Kinase 1/2 inhibitor ruxolitinib (Rux). Patients were treated with efficacy/toxicity guided step up dosing up to 14 days. Retrospective analysis of CIS reduction and clinical outcome was performed. Out of 105 patients treated between March 30th and April 15th, 2020, 14 patients with a CIS ≥ 10 out of 16 points received Rux over a median of 9 days with a median cumulative dose of 135 mg. A total of 12/14 patients achieved significant reduction of CIS by ≥25% on day 7 with sustained clinical improvement in 11/14 patients without short term red flag warnings of Rux-induced toxicity. Rux treatment for COVID-19 in patients with hyperinflammation is shown to be safe with signals of efficacy in this pilot case series for CRS-intervention to prevent or overcome multiorgan failure. A multicenter phase-II clinical trial has been initiated (NCT04338958).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents / therapeutic use*
  • Betacoronavirus / drug effects
  • Betacoronavirus / immunology
  • Betacoronavirus / pathogenicity
  • Clinical Trials as Topic
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / enzymology
  • Coronavirus Infections / immunology
  • Coronavirus Infections / virology
  • Cytokine Release Syndrome / drug therapy*
  • Cytokine Release Syndrome / enzymology
  • Cytokine Release Syndrome / immunology
  • Cytokine Release Syndrome / virology
  • Cytokines / antagonists & inhibitors
  • Cytokines / genetics
  • Cytokines / immunology
  • Drug Administration Schedule
  • Female
  • Gene Expression Regulation
  • Humans
  • Immunity, Innate / drug effects
  • Inflammation
  • Janus Kinase 1 / antagonists & inhibitors*
  • Janus Kinase 1 / genetics
  • Janus Kinase 1 / immunology
  • Janus Kinase 2 / antagonists & inhibitors*
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / immunology
  • Male
  • Middle Aged
  • Pandemics
  • Patient Safety
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / enzymology
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / virology
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / therapeutic use*
  • Retrospective Studies
  • Severe Acute Respiratory Syndrome / drug therapy*
  • Severe Acute Respiratory Syndrome / enzymology
  • Severe Acute Respiratory Syndrome / immunology
  • Severe Acute Respiratory Syndrome / virology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / virology
  • Treatment Outcome

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • INCB018424
  • Protein Kinase Inhibitors
  • Pyrazoles
  • JAK1 protein, human
  • JAK2 protein, human
  • Janus Kinase 1
  • Janus Kinase 2

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2

Associated data

  • ClinicalTrials.gov/NCT04338958