Ruxolitinib for Severe COVID-19-Related Hyperinflammation in Nonresponders to Steroids

Acta Haematol. 2021;144(6):620-626. doi: 10.1159/000516464. Epub 2021 Jun 10.

Abstract

Introduction: Currently, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is a major public health problem worldwide. Although most patients present a mild infection, effective strategies are required for patients who develop the severe disease. Anti-inflammatory treatment with JAK inhibitors has been considered in SARS-CoV-2.

Methods: In this study, we presented our experience in a group of severe SARS-CoV-2 Chilean patients. This prospective study was performed on consecutive patients presenting severe respiratory failure owing to COVID-19 or high-risk clinical condition associated with SARS-CoV-2, and who were treated with ruxolitinib for management of associated inflammation. Overall, 18 patients presenting SARS-CoV-2 viral-induced hyperinflammation were treated with ruxolitinib, with 16 patients previously treated with steroids, 4 with tocilizumab, and 3 with both treatments.

Results: Ten patients evolved with favorable response, including 7 patients admitted with severe respiratory failure (PaFi less than 200 mm Hg in high-flow nasal cannula), presenting complete regression of hyperinflammation, regression of the lung lesions, and subsequent discharge. In the remaining 8 patients, 25% showed reduced inflammation, but early discharge was not achieved owing to the slow evolution of respiratory failure. Unfortunately, 3 patients demonstrated a severe respiratory failure. The early initiation of ruxolitinib was found to be associated with better clinical evolution (p < 0.005).

Conclusion: In this study, ruxolitinib resolved hyperinflammatory state in 55% of the patients, regardless of the previous steroid or tocilizumab therapy. Unfortunately, few patients demonstrated severe evolution despite ruxolitinib therapy. Notably, the treatment starting time appears to play an important role in achieving good outcomes. Further validation in randomized controlled trials is crucial.

Keywords: Coronavirus disease-19; Inflammation; Janus kinase/signal transducer and activator of transcription; Ruxolitinib.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • COVID-19 / complications*
  • COVID-19 / pathology
  • COVID-19 / virology
  • Chile
  • Female
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / etiology
  • Male
  • Middle Aged
  • Nitriles / adverse effects
  • Nitriles / therapeutic use*
  • Prospective Studies
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use*
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Respiratory Insufficiency / drug therapy
  • Respiratory Insufficiency / etiology
  • SARS-CoV-2 / isolation & purification
  • Steroids / therapeutic use
  • Thrombocytopenia / etiology
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Nitriles
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • Steroids
  • ruxolitinib
  • tocilizumab