Interleukin-6 blockade with sarilumab in severe COVID-19 pneumonia with systemic hyperinflammation: an open-label cohort study

Ann Rheum Dis. 2020 Oct;79(10):1277-1285. doi: 10.1136/annrheumdis-2020-218122. Epub 2020 Jul 3.

Abstract

Objectives: To assess the safety and efficacy of interleukin (IL)-6 blockade with sarilumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation.

Methods: We conducted an open-label study of sarilumab in severe COVID-19 pneumonia (PaO2/FiO2 <300 mm Hg) with hyperinflammation (elevated inflammatory markers and serum IL-6 levels). Sarilumab 400 mg was administered intravenously in addition to standard of care and results were compared with contemporary matched patients treated with standard of care alone. Clinical improvement, mortality, safety and predictors of response were assessed at 28 days.

Results: Twenty-eight patients were treated with sarilumab and 28 contemporary patients receiving standard of care alone were used as controls. At day 28 of follow-up, 61% of patients treated with sarilumab experienced clinical improvement and 7% died. These findings were not significantly different from the comparison group (clinical improvement 64%, mortality 18%; p=NS). Baseline PaO2/FiO2 ratio >100 mm Hg and lung consolidation <17% at CT scan predicted clinical improvement in patients treated with sarilumab. Median time to clinical improvement in patients with lung consolidation <17% was shorter after sarilumab (10 days) than after standard treatment (24 days; p=0.01). The rate of infection and pulmonary thrombosis was similar between the two groups.

Conclusions: At day 28, overall clinical improvement and mortality in patients with severe COVID-19 were not significantly different between sarilumab and standard of care. Sarilumab was associated with faster recovery in a subset of patients showing minor lung consolidation at baseline.

Keywords: anti-inflammatory agents, non-steroidal; inflammation; therapeutics.

Publication types

  • Observational Study

MeSH terms

  • Administration, Intravenous
  • Anti-Bacterial Agents / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antiviral Agents / therapeutic use
  • Azithromycin / therapeutic use
  • Bacteremia / epidemiology
  • Betacoronavirus
  • C-Reactive Protein / immunology*
  • COVID-19
  • COVID-19 Drug Treatment
  • Cohort Studies
  • Coinfection / epidemiology
  • Coronavirus Infections / diagnostic imaging
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / immunology
  • Coronavirus Infections / mortality
  • Drug Combinations
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Humans
  • Hydroxychloroquine / therapeutic use
  • Inflammation / immunology*
  • Interleukin-6 / immunology*
  • Italy
  • Lopinavir / therapeutic use
  • Lung / diagnostic imaging
  • Male
  • Middle Aged
  • Noninvasive Ventilation
  • Oxygen Inhalation Therapy
  • Pandemics
  • Pneumonia, Viral / diagnostic imaging
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / mortality
  • Proportional Hazards Models
  • Receptors, Interleukin-6 / antagonists & inhibitors
  • Ritonavir / therapeutic use
  • SARS-CoV-2
  • Severity of Illness Index
  • Time Factors
  • Tomography, X-Ray Computed
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Antibodies, Monoclonal, Humanized
  • Antiviral Agents
  • Drug Combinations
  • Enzyme Inhibitors
  • IL6 protein, human
  • IL6R protein, human
  • Interleukin-6
  • Receptors, Interleukin-6
  • lopinavir-ritonavir drug combination
  • Lopinavir
  • Hydroxychloroquine
  • Azithromycin
  • C-Reactive Protein
  • sarilumab
  • Ritonavir