Coronavirus Disease 2019 Treatment: A Review of Early and Emerging Options

McCreary, Erin K; Pogue, Jason M

Tocilizumab is a humanized monoclonal antibody that inhibits both membrane-bound and soluble interleukin-6 (IL-6) receptors. Interleukin-6, which is secreted by monocytes and macrophages, is one of the main drivers of immunologic response and symptoms in patients with cytokine-release syndrome (CRS). Although tocilizumab was first approved by the FDA in 2010 for the treatment of rheumatoid arthritis, it has gained traction in recent years for treatment of patients with CRS following chimeric antigen receptor T-cell (CAR T) therapy as a corticosteroid-sparing agent [42] . Indeed, it received FDA approval for severe or life-threatening CAR T-associated CRS in 2017 due to its efficacy and safety profile. Although criteria for grading CRS severity varies by cancer center, it has been proposed to administer tocilizumab to CRS patients with any of the following: oxygen requirement <40%, hypotension responsive to fluids or a low dose of a single vasoactive agent, or Grade 2 organ toxicity as defined by the Common Terminology Criteria for Adverse Events [43] . Interleukin-6 antagonism may make a patient more susceptible to bacterial infection and has been associated with neutropenia and thrombocytopenia in patients receiving chronic therapy with tocilizumab for giant cell arteritis or rheumatoid arthritis. In a case series of 53 adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia, Grade 3 CRS or higher was associated with increased risk of subsequent infection, but it was unclear whether tocilizumab or corticosteroid use promoted this risk [44] . There were no reported adverse events in the 60 tocilizumab-treated patients submitted to the FDA for the CRS indication, which recommends a maximum of 4 doses for treatment [45] .