In Covid-19 patients with pneumonia and oxygen needs, tocilizumab reduces the risk of progression to a severe form, resuscitation and intubation. The very significant impact of this treatment for systemic inflammatory diseases, an anti-IL6R drug, has been demonstrated in a randomized trial set up in a very short time. A major event that changes the prognosis of the disease and the future congestion of resuscitation.
- An anti-inflammatory drug would prevent the inflammatory shock that aggravates many cases of Covid-19 on the 7th day
- This trial was carried out by a platform bringing together French researchers to test the effectiveness of treatments
This is news that we were impatiently awaiting, in patients hospitalized for pneumonia with oxygen needs (hypoxemic pneumonia up to WHO stage 5) in the context of Covid-19: tocilizumab, an IL6 receptor inhibitor usually used in the treatment of rheumatoid arthritis, statistically reduces the risk of intubation and death (primary endpoint).
These results (not detailed) were presented in press conference of the AP-HP and are from a randomized study versus placebo, to be published in a peer-reviewed journal. A news that is likely to profoundly change the management and prognosis of this disease and quality research mounted in a very short time.
An inflammatory turn to 7th day
In patients suffering from a “hypoxemic” form of Covid-19 pneumonia (requiring oxygen supply), it is accepted that a “cytokine storm”, with strong release of IL6 of immunological origin, can occur in some people and this is what can lead them to acute respiratory failure (ARDS) and to resuscitation with intubation. This cytokine storm is, moreover, probably not insignificant for the prognosis of the state of the lungs for the patients who survive, with a risk of pulmonary fibrosis and subsequent respiratory failure.
There is a persistence of the virus in the lung and the blood, but it is this inflammatory turn of the disease of immune origin which makes all the seriousness of Covid-19, in the majority of cases (there are cases superinfection and pulmonary embolism), and which is the main responsible for the congestion of resuscitation (more patients and longer.
A randomized multicenter trial
This trial randomized, multicenter, open-label study, compared in a controlled manner tocilizumab, a monoclonal antibody which blocks the interleukin-6 receptor, and which is used in particular in the treatment of rheumatoid arthritis and Horton’s disease, with the usual treatment .
Because of the incredible concentrations of IL-6 which can be reached in the blood of these patients, an inhibitor of the IL6 receptor was preferred to an anti-IL6, because it is more easily blocked than a large number of molecules. An injection of 8 mg per kilogram of body weight was given, which could be followed by another three days later if there was no response or increased oxygen requirements.
The patients were selected on the basis of hospitalization for “hypoxemic” Covid-19 pneumonia, moderate or severe, but not requiring resuscitation at the time of admission (simple oxygen therapy, in addition to supportive treatment). The primary endpoint was a combined endpoint combining the use of ventilation (mechanical or non-invasive) or death on D14.
A study of 129 patients
A total of 129 patients were randomized, including 65 in the usual treatment group with administration of tocilizumab (on D1 and D3) and 64 in the usual treatment alone group. The primary endpoint was reached in a very significantly lower proportion of patients in the tocilizumab arm. Due to the modest size of the trial, the benefit is therefore certainly important from a medical point of view.
The results of this trial are submitted for publication and they must, of course, be independently confirmed in another trial. Given the context of the pandemic and the importance of these results, the researchers (and the sponsor) felt obliged to communicate this information, before publication, while continuing the longer follow-up of these patients.
A research structure set up very quickly
This multicenter trial was conducted in record time by the Covid-19 Assistance Publique-Hôpitaux de Paris/Universities/INSERM-REACTing academic research collaboration. Other CORIMUNO trials testing other IL-6 receptor inhibitors and other immunomodulators are currently being analyzed.
The CORIMUNO-19 platform was set up at the start of the pandemic to test the efficacy and tolerance of various treatments in adult patients with severe Covid-19, through a series of randomized, controlled, multicenter trials, which were launched on March 27, 2020. All this demonstrates, if it were still necessary, that very good medical and scientific research can be carried out in “time of war” and without wasting time.
It is a remarkable performance and a result that brings a lot of hope, including in view of the deconfinement, called for by the government. A major step has just been taken.
