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.

Keywords: COVID-19; SARS-CoV2; acute respiratory distress syndrome; interleukin 6.

Figure 1.

Oxygen support requirement following tocilizumab administration. Each bar represents an individual patient from the study population. Changes in color represent changes in oxygen support modality administered over time. Four patients remain intubated at last follow-up. Indicators of hospital discharge (n = 13; circle) and death (n = 2; diamond) are represented.

Figure 2.

Vasopressor support over time among patients requiring mechanical ventilation on the day of tocilizumab administration (n = 21). In sum, 17 patients required norepinephrine at the time of tocilizumab administration (day 0), 16 patients on day 1, 12 patients on day 3, and 3 patients on day 7.

Figure 3.

A, Cytokine profile at time of toclizumab administration. Cytokines were measured using Luminex platform assays. Normal values for IL-6 are 0–5 pg/mL. Although other cytokines showed minimal elevations at time of tocilizumab administration (IL-10, TNF-α, and IFN- γ), IL-6 was the predominant cytokine expressed in SARS-CoV-2 patients. B, Change in CRP after tocilizumab administration. Figure shows the CRP values obtained at initiation and 72 hours post-tocilizumab administration. Tocilizumab administration resulted in a significant reduction in CRP values at 72 hours. C, Body temperature after tocilizumab administration. This figure shows the temperatures of SARS-CoV-2 patients pre- and 24 hours post-tocilizumab. Tocilizumab was associated with a significant reduction in body temperature within 24 hours of administration. Abbreviations: CRP, C-reactive protein; IFN, interferon; IL, interleukin; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TNF, tumor necrosis factor.