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

Author:

Jordan Stanley C1,Zakowski Phillip2,Tran Hai P3,Smith Ethan A3,Gaultier Cyril2,Marks Gregory3,Zabner Rachel2,Lowenstein Hayden2,Oft Jillian2,Bluen Benjamin2,Le Catherine2,Shane Rita3,Ammerman Noriko1,Vo Ashley1,Chen Peter4,Kumar Sanjeev1,Toyoda Mieko1,Ge Shili1,Huang Edmund1

Affiliation:

1. Department of Medicine, Division of Nephrology, Transplant Immunology Laboratory, Transplant Immunotherapy Program, Los Angeles, California, USA

2. Division of Infectious Diseases, Los Angeles, California, USA

3. Department of Pharmacy Services, Los Angeles, California, USA

4. Division of Pulmonary and Critical Care Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA

Abstract

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.

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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