Adding the drug tocilizumab arthritis to routine care for hospitalized patients with severe or urgent covid-19 is no better than standard care alone in improving clinical outcomes at 15 days, new trial finds published by Am BMJ today.
More people died at 15 days in patients receiving tocilizumab, as a result of which the trial was stopped early.
Today’s results contradict earlier speculative studies suggesting the benefit of tocilizumab. However, observational effects are limited by a high risk that they may be due to other unknown (difficult) factors – and some studies have not been peer-reviewed or published in a medical journal.
A randomized trial evaluating tocilizumab in covid-19 patients with severe covid-19 (REMAP-CAP) published as an introduction earlier this month found a beneficial effect of the drug on days off from organ support. 21 days and mortality. Reasons for these seemingly contradictory effects, for example, differences between patient characteristics, need to be evaluated in a future study, the researchers said.
Tocilizumab blocks a specific part of the immune system (interleukin 6) that can become overactive in some patients with covid-19. Doctors believe that this may help reduce the body’s inflammatory response to the virus and eliminate some of the most severe effects of the disease, but its effects are not well explained. .
To test this theory, Brazilian-based researchers conducted a randomized controlled trial comparing tocilizumab in addition to conventional care alone in patients admitted to hospital with covid-19 heavy or urgent.
Their findings are based on 129 relatively young adults (average age 57 years) with covid-19 tested at nine hospitals in Brazil between 8 May and 17 July 2020.
Patients were receiving extra oxygen or mechanical ventilation and had abnormal levels of at least two chemicals associated with inflammation in their blood.
Patients were randomly divided into two groups: 65 received tocilizumab in addition to routine care and 64 received routine care alone.
Other potentially important factors, such as underlying conditions and the use of other medications, were noted, and all patients were monitored for 15 days.
By day 15, 18 patients (28%) in the tocilizumab group and 13 (20%) in the usual care group had mechanical ventilation or died.
Death occurred at 15 days in 11 (17%) patients in the tocilizumab group compared with 2 (3%) in the standard care group.
The increased number of deaths in the tocilizumab group raised safety concerns and the trial was adjourned early. In both groups, deaths were due to covid-19-related respiratory failure or organ dysfunction.
The researchers point out some limitations including a small sample size, which affects the chances of finding a real effect. However, consistent results after adjusting for levels of respiratory support required by patients at the start of the trial suggested that the findings would stand up to scrutiny.
Thus, the researchers conclude that, in patients with severe or acute covid-19, “tocilizumab in addition to conventional care was not superior to conventional care alone in improving clinical status at 15 days and may increase mortality. “
And they say these results “raise questions about an anti-inflammatory approach in the treatment of covid-19 beyond corticosteroids.”
Source:
Magazine Reference:
Veiga, VC, et al. (2021) Effect of tocilizumab on clinical outcomes at 15 days in patients with major or acute coronavirus disease 2019: a randomized controlled trial. The BMJ. doi.org/10.1136/bmj.n84.