medwireNews: Adding the interleukin (IL)-6 receptor inhibitor tocilizumab to standard care reduces the risk for progression to mechanical ventilation or death among hospitalized patients with COVID-19 pneumonia, show findings from the EMPACTA randomized controlled trial.
However, tocilizumab did not significantly reduce the risk for a number of secondary outcomes, including all-cause mortality, report the investigators in The New England Journal of Medicine.
The study included 377 participants from six countries (USA, Mexico, Kenya, South Africa, Peru, and Brazil) without the need for mechanical ventilation at baseline who were randomly assigned to receive two doses of intravenous tocilizumab 8 mg/kg (to a maximum of 800 mg/dose) or placebo in addition to local standard care. The majority of patients in both groups received systemic glucocorticoids (80.3–87.5%) and/or antiviral treatment (78.7–78.9%) during the trial or in the 7 days beforehand.
EMPACTA “emphasized the enrollment of patients from high-risk and racial and ethnic minority groups” in order “[t]o directly address the discrepancy between the overrepresentation of racial and ethnic minorities with Covid-19 disease and the underrepresentation of these minorities in Covid-19 trials,” say Shalini Mohan (Genentech, South San Francisco, California, USA) and colleagues.
They note that a quarter of participants were older than 65 years and more than three-quarters had one or more pre-existing conditions. In all, 56.0% of patients were of Hispanic or Latino ethnicity, while 14.9% were Black, 12.7% American or Alaskan Native, and 12.7% Non-Hispanic White. The majority (80.6%) were enrolled in the USA.
During 28 days of follow-up, 12.0% of 249 patients in the tocilizumab arm experienced the primary composite outcome of mechanical ventilation or death, as did 19.3% of 128 participants in the placebo arm, translating into a significant 44% reduced risk with the IL-6 inhibitor. Mohan and team note that these findings were consistent in a subgroup analysis categorizing participants by race/ethnicity.
However, all-cause mortality rates during the 28-day period did not significantly differ in the tocilizumab and placebo groups, at 10.4% and 8.6%, respectively.
There were also no significant between-group differences in the median time to improvement in clinical status on a 7-point ordinal scale (6.0 vs 7.0 days) and the median time to hospital discharge or readiness for discharge (6.0 vs 7.5 days) among patients treated with tocilizumab versus placebo.
In the safety analysis, a comparable 50.8% of patients in the tocilizumab group and 52.8% of those given placebo experienced adverse events (AEs) over a total follow-up of 60 days, while 15.2% and 19.7%, respectively, experienced serious AEs. Serious infections were reported in a corresponding 5.2% and 7.1% of participants.
Taken together, the EMPACTA findings suggest “that tocilizumab may add to the potential benefit of antiviral treatment and glucocorticoids,” say the investigators.
These conclusions differ from those of the BACC Bay Tocilizumab, RCT-TCZ, and CORIMUNO-TOCI-1 trials, which broadly found no significant benefits of tocilizumab for patients with COVID-19. Mohan and team note that these trials included participants with different baseline characteristics and use of other treatments compared with EMPACTA.
“[O]ur results reflect the most up-to-date standard of care, especially considering the approval of remdesivir in the United States,” they add.
The researchers conclude: “Ongoing trials are under way to provide clarity on the patient subgroups that are most likely to benefit from specific immunomodulatory therapies.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2020 Springer Healthcare Ltd, part of the Springer Nature Group
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