Tocilizumab, a monoclonal anti-IL-6-receptor blocking antibody,

has been proposed as a therapeutic agent to mitigate hyperinflammation associated with COVID-19. Tocilizumab is FDA-approved for various rheumatologic conditions as well as cytokine release syndrome associated with CAR-T cell therapy.

Why are are interleukin-6 (IL-6) receptor antagonists considered for treatment?

Some patients with COVID-19 develop a hyperinflammatory syndrome that is characterized by elevations in proinflammatory cytokines and multiorgan dysfunction also known as the immunopathology of SARS-CoV-2 infection. The significance of these findings is unclear, however early descriptions found that those with elevated IL-6 levels and evidence of hyperinflammation had increased rates of more severe disease

Among hospitalized patients, tocilizumab showed a trend toward reduced mortality at 28 days compared to no tocilizumab treatment (RR: 0.91; 95% CI: 0.79, 1.04; moderate CoE). Tocilizumab demonstrated a lower relative risk of clinical deterioration, defined as death, need for mechanical ventilation, ECMO, or ICU admission, compared to placebo/usual care, RR: 0.83 (95% CI: 0.77, 0.89; moderate CoE). Four studies were not blinded, while in the remaining three trials healthcare personnel and outcome assessors were blinded. The panel noted that tocilizumab causes a decline in CRP levels, which if obtained would reveal the treatment arm designations of the patients, therefore introducing bias for the more subjectively measured outcomes of clinical deterioration and serious adverse events.

Sarilumab, another IL-6 receptor antagonist, is currently FDA-approved for rheumatoid arthritis (RA).

Both RECOVERY study and REMAP CAP (the two tocilizumab trials that reported a benefit) initiated treatment early (randomization at median of two days of hospitalization in RECOVERY; <24 hours in the ICU for REMAP-CAP), suggesting tocilizumab may be more beneficial early in people with rapidly progressive disease.

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