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Interleukin-6 blockade has long been proposed as a treatment for severe COVID-19, but randomized trials have yielded conflicting messages. Now, two new studies of tocilizumab (COVACTA and REMAP-CAP) have been published. REMAP-CAP in particular represents progress toward defining the group of patients who benefit from this agent.
In COVACTA (conducted before dexamethasone was established as standard of care for people with severe or critical COVID-19 [N Engl J Med 2021; 384:693]), 452 participants hospitalized with severe COVID-19 were randomized 2:1 to receive tocilizumab or placebo. At baseline, about 37% of participants had already been receiving mechanical ventilation for 4 to 5 days. A small proportion of patients received glucocorticoids (19.4% [tocilizumab] and 28.5% [placebo]). Tocilizumab did not improve clinical status or reduce mortality at day 28, although time to hospital discharge (or readiness for discharge) and duration of intensive care unit (ICU) stay both appeared to be shorter in the tocilizumab group.
Investigators for REMAP-CAP randomized participants within 24 hours of starting respiratory or cardiovascular organ support in an ICU to receive open-label tocilizumab (353 patients), sarilumab (48), or standard care (402). At baseline, most participants required only high-flow oxygen (29%) or noninvasive ventilation (42%). Median time from hospital admission to enrollment was 1.2 days. Most patients (>80%) received glucocorticoids. Compared with standard care, tocilizumab was associated with more days free of organ support and lower in-hospital mortality.
Rosas IO et al. Tocilizumab in hospitalized patients with severe Covid-19 pneumonia. N Engl J Med 2021 Feb 25; [e-pub]. (https://doi.org/10.1056/NEJMoa2028700)
Gordon AC et al. Interleukin-6 receptor antagonists in critically ill patients with Covid-19. N Engl J Med 2021 Feb 25; [e-pub]. (https://doi.org/10.1056/NEJMoa2100433)
Comment
Of all the medical interventions considered for management of severe or critical COVID-19, tocilizumab has been one of the most disputed. This agent seems to improve clinical outcomes in patients who have recently been admitted to ICU-level care. But what's the difference between the positive results in REMAP-CAP and the negative or mixed results in COVACTA and previous tocilizumab trials? Perhaps using tocilizumab along with glucocorticoids (common in REMAP-CAP but not before) — and early initiation — all matter. Will the benefit of using tocilizumab in combination with glucocorticoids be generalizable to other patient populations? Data from the RECOVERY trial (available only in a non–peer-reviewed preprint) suggest the answer to this critical question is yes.