Critically ill covid-19 patients treated with the anti-inflammatory tocilizumab are almost twice as likely to have a better course of their disease than patients who do not receive the drug. This was measured on the basis of survival from hospital admission and the duration of ventilation and other support for organs they needed in intensive care.
The results now announced are the first results of a worldwide study of the efficacy of various immune-blockers in critically ill covid-19 patients. The study has not yet been peer reviewed or published. But because of its immediate significance for treating the sickest patients, the researchers are now publishing their results anyway.
Patients with the most severe form of covid-19 often experience an overreaction of the immune system, causing serious infections throughout the body. Immune inhibitors reduce the body’s response.
More than 300 patients took part in the study. The static probability that the study results are correct, according to independent evaluators of the study, is almost 100 percent.
Not yet more concrete
The researchers are not yet able to say how much less death occurs in the group that received tocilizumab and the control group that did not. It is also not yet clear how much shorter the patients from the tocilizumab group were in the ICU and on devices that took over their vital functions.
“That has to do with how such research works,” explains Marc Bonten. He is head of the medical microbiology department at UMC Utrecht and one of the principal investigators. “We collect the data in the hospitals. It then goes to an independent group of statisticians who start calculating.”
Their calculations then go to the independent Data and Safety Monitoring Board. “They reported to us on Tuesday that it is certain with a statistical probability of 99.8 percent that tocilizumab provides better outcomes in these patients. Normally we already call things with a lower statistical probability certain,” says Bonten.
“It is therefore certain that tocilizumab improves the course of covid-19 in very seriously ill patients. And we have defined ‘better’ as less mortality, shorter stay in the ICU and shorter dependence on vital signs support.”
“We have now released it because all participating hospitals need to know,” says Bonten. “Doctors need to know and researchers working on tocilizumab studies should also know to see if they can already see the same effect. Then we move on to the analysis of the data.”
Immune inhibitor
Tocilizumab is an existing medicine for rheumatic diseases. It is the second agent whose efficacy against covid-19 has now been proven. It was previously found that the anti-inflammatory dexamethasone, a corticosteroid, significantly improves the course of covid-19 in critically ill patients.
The researchers are now continuing to further analyze and make more concrete the gains that can be achieved by giving tocilizumab to critically ill covid patients.
They will also compare the effect of tocilizumab in severe covid-19 with the effect of other immune inhibitors. The data has already been collected, and the results of this part of the study are expected to come soon.
REMAP-CAP trial
The study, of which the first results have now been announced, is part of the REMAP-CAP trial, a large international study in eight Dutch hospitals, 48 hospitals in 15 other European countries and another 200 hospitals in Australia, New Zealand, the Netherlands. USA and Canada. UMC Utrecht coordinates the European part of the study, which is led by Imperial College London.
The REMAP-CAP trial is a so-called platform trial. After years of preparations, which actually started after the swine flu pandemic in 2009, the study started in 2019. These preparations took so long because the design of the study had to comply with different rules in all participating countries. Initially, the study began as a study of the treatment of severe pneumonia.
But the research protocol is designed in such a way that it can be adjusted immediately if there is reason to do so. In March, the researchers started to focus on treating severe covid that is very often associated with pneumonia. Then the research protocol was ready.
This has led to large-scale research into effective treatments for the first time during a pandemic. Until now, these investigations have always only started after the pandemic or epidemic had already passed. This was the case, for example, with the Mexican flu, but also with the large Q fever outbreak that hit the Netherlands in the years 2007-2010.
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