Compassionate Use of Tocilizumab for Treatment of SARS-CoV-2 Pneumonia.

Abstract

BACKGROUND:

Preliminary data from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia patients indicate that a cytokine storm may increase morbidity and mortality. Tocilizumab (anti-IL-6R) is approved by the Food and Drug Administration for treatment of cytokine storm associated with chimeric antigen receptor T-cell therapy. Here we examined compassionate use of tocilizumab in patients with SARS-CoV-2 pneumonia.

METHODS:

We report on a single-center study of tocilizumab in hospitalized patients with SARS-CoV-2 pneumonia. All patients had confirmed SARS-CoV-2 pneumonia and oxygen saturations <90% on oxygen support with most intubated. We examined clinical and laboratory parameters including oxygen and vasopressor requirements, cytokine profiles, and C-reactive protein (CRP) levels pre- and post-tocilizumab treatment.

RESULTS:

Twenty-seven SARS-CoV-2 pneumonia patients received one 400 mg dose of tocilizumab. Interleukin (IL)-6 was the predominant cytokine detected at tocilizumab treatment. Significant reductions in temperature and CRP were seen post-tocilizumab. However, 4 patients did not show rapid CRP declines, of whom 3 had poorer outcomes. Oxygen and vasopressor requirements diminished over the first week post-tocilizumab. Twenty-two patients required mechanical ventilation; at last follow-up, 16 were extubated. Adverse events and serious adverse events were minimal, but 2 deaths (7.4%) occurred that were felt unrelated to tocilizumab.

CONCLUSIONS:

Compared to published reports on the morbidity and mortality associated with SARS-CoV-2, tocilizumab appears to offer benefits in reducing inflammation, oxygen requirements, vasopressor support, and mortality. The rationale for tocilizumab treatment is supported by detection of IL-6 in pathogenic levels in all patients. Additional doses of tocilizumab may be needed for those showing slow declines in CRP. Proof of efficacy awaits randomized, placebo-controlled clinical trials.

• Authors: Stanley C Jordan, Phillip Zakowski, Hai P Tran, Ethan A Smith, Cyril Gaultier, Gregory Marks, Rachel Zabner, Hayden Lowenstein, Jillian Oft, Benjamin Bluen, Catherine Le, Rita Shane, Noriko Ammerman, Ashley Vo, Peter Chen, Sanjeev Kumar, Mieko Toyoda, Shili Ge, Edmund Huang
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 71 Issue 12 Pg. 3168-3173 (12 15 2020) ISSN: 1537-6591 [Electronic] United States
• PMID: 32575124 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Chemical References

• Antibodies, Monoclonal, Humanized
• tocilizumab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized
• COVID-19
• Compassionate Use Trials
• Humans
• Male
• Middle Aged
• SARS-CoV-2
• Treatment Outcome