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Elevated interleukin-6 (IL-6) levels are linked to worse outcomes in patients with COVID-19, but it remains unclear whether blocking this cytokine confers clinical benefit. Although large randomized trials have failed to show that tocilizumab, an anti–IL-6 receptor antibody, reduces mortality, some studies have suggested that the agent lowers risk for progression to mechanical ventilation (NEJM JW Infect Dis Jan 4 2021; [e-pub] and N Engl J Med 2020 Dec 17; [e-pub]) and shortens time to hospital discharge. Now, a small randomized trial in Brazil adds to the confusion.
In all, 129 patients requiring supplemental oxygen or mechanical ventilation who also had elevated inflammatory biomarkers were randomized to receive tocilizumab plus standard care or standard care alone. The trial was stopped early because of substantially higher mortality at day 15 in the tocilizumab group (17%) compared with the standard care group (3%). By day 28, the difference in mortality between the tocilizumab group and standard care group was no longer statistically significant (21% and 9%; P=0.07).
Veiga VC et al. Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: Randomised controlled trial. BMJ 2021 Jan 20; 372:n84. (https://doi.org/10.1136/bmj.n84)
Comment
This small study did not demonstrate any benefit of tocilizumab and raised the possibility of increased mortality. Notably, standard care in this trial often included corticosteroids, but also drugs now known to lack benefit (e.g., hydroxychloroquine, azithromycin); remdesivir was not available. Larger trials have not shown excess risk for death or adverse events with tocilizumab, so the current study appears to be an outlier. We eagerly await publication of the REMAP-CAP trial results (preliminary findings from this large randomized trial indicate a reduction in mortality when tocilizumab is administered within 24 hours of initiating organ support in an intensive care unit). Whether tocilizumab has clinical benefit when given to the right patient at the right time is still being fiercely debated.