Litcius/Paper detail

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

Stanley C. Jordan, P. Zakowski, Hai Tran, Ethan Smith, C Gaultier, Gregory Marks, Rachel Zabner, Hayden Lowenstein, Jillian Oft, Benjamin Bluen, C. Le, Rita Shane, Noriko Ammerman, Ashley Vo, Peter Chen, Sanjeev Kumar, Mieko Toyoda, Shili Ge, Edmund Huang

2020Clinical Infectious Diseases89 citationsDOIOpen Access PDF

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.

Topics & Concepts

TocilizumabMedicineCoronavirus disease 2019 (COVID-19)Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Pneumonia2019-20 coronavirus outbreakVirologyCompassionate UseBetacoronavirusCoronavirusViral pneumoniaImmunologyInternal medicineClinical trialOutbreakInfectious disease (medical specialty)DiseaseRheumatoid arthritisCOVID-19 Clinical Research StudiesSARS-CoV-2 and COVID-19 ResearchLong-Term Effects of COVID-19