Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in Milan, Italy

Eur J Intern Med. 2020 Jun:76:36-42. doi: 10.1016/j.ejim.2020.05.011. Epub 2020 May 21.

Abstract

Background: Tocilizumab, a humanized monoclonal antibody, targets IL-6 receptors blocking downstream pro-inflammatory effects of IL-6. In preliminary reports it was suggested to be beneficial in patients with severe COVID-19.

Methods: In this open-label prospective study we describe clinical characteristics and outcome of 51 patients hospitalized with confirmed and severe COVID-19 pneumonia treated with tocilizumab intravenously. All patients had elevated IL-6 plasma level (>40 pg/mL) and oxygen saturation <93% in ambient air. Clinical outcomes, oxygen support, laboratory data and adverse events were collected over a follow-up of 30 days.

Results: Forty-five patients (88%) were on high-flow oxygen supplementation, six of whom with invasive ventilation. From baseline to day 7 after tocilizumab we observed a dramatic drop of body temperature and CRP value with a significant increase in lymphocyte count (p<0.001). Over a median follow-up time of 34 days from tocilizumab, 34 patients (67%) showed an improvement in their clinical severity class; 31 were discharged; 17 (33%) showed a worsening of their clinical status, of these 14 died (27%). The mortality rate was significantly associated with mechanical ventilation at baseline (83.3% vs 20% of patients on non-invasive oxygen support; p=0.0001). The most frequent side effects were an increase of hepatic enzymes (29%), thrombocytopenia (14%), and serious bacterial and fungal infections (27%).

Conclusion: Tocilizumab exerts a rapidly beneficial effect on fever and inflammatory markers, although no significant impact on the clinical outcome can be inferred by our results. Critically ill patients seem to have a high risk of serious infections with this drug.

Keywords: COVID-19; IL-6 inhibitors; tocilizumab.

MeSH terms

  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antiviral Agents / adverse effects
  • Betacoronavirus / drug effects
  • Betacoronavirus / isolation & purification
  • COVID-19
  • Coronavirus Infections* / blood
  • Coronavirus Infections* / epidemiology
  • Coronavirus Infections* / physiopathology
  • Coronavirus Infections* / therapy
  • Female
  • Fever / diagnosis
  • Fever / drug therapy
  • Humans
  • Italy / epidemiology
  • Lymphocyte Count / methods
  • Male
  • Middle Aged
  • Outcome and Process Assessment, Health Care
  • Pandemics*
  • Pneumonia, Viral* / blood
  • Pneumonia, Viral* / diagnosis
  • Pneumonia, Viral* / drug therapy
  • Pneumonia, Viral* / epidemiology
  • Pneumonia, Viral* / etiology
  • Pneumonia, Viral* / physiopathology
  • Pneumonia, Viral* / therapy
  • Receptors, Interleukin-6 / antagonists & inhibitors*
  • Respiration, Artificial / methods*
  • Respiratory Insufficiency* / etiology
  • Respiratory Insufficiency* / therapy
  • Retrospective Studies
  • SARS-CoV-2

Substances

  • Antibodies, Monoclonal, Humanized
  • Antiviral Agents
  • Receptors, Interleukin-6
  • tocilizumab