Le tocilizumab n'est pas efficace contre les formes graves de la Covid-19<

Among all the treatment under study to fight the COVVI-19, tocilizumab seems to be one of the most promising.This therapeutic antibody blocks the receptors of the IL-6, thus preventing the deleterious action of this pro-inflammatory molecule involved in the cytokinic storm observed in the serious forms of the disease.It has already demonstrated its effectiveness to treat rheumatoid arthritis.

In Brazil, nine hospitals have participated in an Open-Label randomnized clinical trial, it means that patients know if they receive a placebo or treatment, and doctors know what they administer, it is the opposite of adouble blind test.The results appeared at the beginning of January in theBmj journal.

No effect of tocilizumab on mortality

This test was conducted with 129 people, mainly men, who suffer from a serious form of COVID-19 requiring oxygen intake or mechanical ventilation.They were separated into two groups of the same size, the first was administered with intravenous tocilizumab up to 8mg/kg for fifteen days and the second group, a placebo according to the same conditions.All patients have received standard care in their state.Note that in Brazil, hydroxychloroquine and azithromycin are among the drugs authorized by health authorities.Several people were treated with one of its two molecules before the start of the clinical trial.

After 15 days, treatment at tocilizumab did not significantly reduce ventilation or mortality needs (28 %) in comparison with the group that received the placebo (20 %).There were 11 deaths in the Tocilizumab group against 3 in the placebo group.At 28 days, the results were no longer statistically significant and therefore could not be analyzed.Finally, tocilizumab has not caused more unwanted side effects than placebo.

A ineffective drug against the serious forms of COVVI-19

Indeed, it appears that tocilizumab has failed to reduce the rate of IL-6;It was even more important than that measured in patients in the placebo group.A surprising result since tocilizumab was designed to limit the action of IL-6 by blocking its receiver;Unfortunately, the mechanisms highlighted in the laboratory do not always demonstrate their effectiveness during clinical trials.

Public assistance-Hôpitaux de Paris had also conducted a clinical trial on tocilizumab, the results of which were published last fall.He had been carried out on a similar workforce and also concluded that tocilizumab does not reduce mortality after 28 days.Although it has many limits, such as the size of the workforce, or it is an open-label clinical trial less rigorous than a clinical trial in double blind, this study is added to thosewhich indicate that tocilizumab is not effective in limiting the serious forms of COVID-19.Currently, only corticosteroids, such as dexamethasone, seem to effectively reduce the inflammatory state of COVID patients.

COVID-19: The first tests on tocilizumab are confirmed

Insuch article published on October 22, 2020

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In some patients, suffering from COVID-19 and moderate to severe pneumonia, the hyperinflammatory state can lead to acute respiratory failure and death.As part of the reacting multidisciplinary consortium, researchers from the Corimuno-19 platform continued the observations started last March in order to confirm the effects of tocilizumab, an anti-receiver antibody from the interleukin-6.

Tocilizumab is a monoclonal antibody that blocks the interleukin-6 cytokine receiver in patients with COVVI-19 and moderate to severe pneumonia.The final results of the randomized trial, open and multicenter controlled and multicenter of tocilizumab, started on March 27, are published after review by peers on October 20, 2020 in the journal Jama Internal Medicine.

The final results of this test-conducted by the collaboration with academic research COVVI-19 public assistance-Hospitals of Paris/University Paris-Saclay/University of Paris/Inserm-Reacting, confirm the preliminary results communicated on April 27, 2020.They should be corroborated independently by additional tests.

Tocilizumab avoids worsening pneumonia

Patients included were hospitalized for moderate to severe COVVI-19 pneumonia, requiring at least 3 l/min of oxygen but without recourse to resuscitation at the time of their admission.The criterion of primary judgment on which the analysis was based to judge the effectiveness of the treatment was the combination of the need for ventilation (mechanical or non -invasive) or the death at J+14.

In total, 130 median age 64 years old age were included in this open randomized clinical trial: 67 for usual treatment and 63 for tocilizumab associated with the usual treatment.In inclusion, the median oxygen needs were 5L/min. La proportion de patients ayant nécessité une ventilation non invasive, une intubation ou étant décédés au 14^e jour était de 36 % avec les soins usuels et de 24 % avec le tocilizumab.No difference in mortality at 28 days was found between the two groups, 11.1 % and 11.9 %, respectively.

Ainsi, au 14^e jour, le risque de mourir ou d'avoir recours à la ventilation non invasive ou mécanique a été diminué de 33 % dans le groupe traité par le tocilizumab.The proportion of patients who had to be transferred to resuscitation was halved in the Tocilizumab group (18 %) compared to the usual processing arm (36 %).

The percentage of patients who left the hospital on day 28 was greater in the tocilizumab group than in the usual treatment group: 83 % versus 73 %.

Finally, tocilizumab has not caused more side effects than usual treatment.Several Corimuno trials testing other immunomodulators, are being analyzed and the combination of tocilizumab at dexamethasone is tested in another Corimuno protocol.

Tocilizumab: What can we expect?

Article by Julien Hernandez, published on May 4, 2020

Communication without raw data from Public Assistance-Hospitals de Paris suggests that tocilizumab could be useful in severe cases of COVVI-19.What can we expect from this medication?

Public assistance-Hôpitaux de Paris (AP-HP), in a statement, says that tocilizumab would be effective in limiting the use of respiratory ventilation and the number of deaths to 14 days, severe COVID-19 patients but without'No raw data is provided.It will be necessary to wait for the publication of the study in the medical literature to judge the quality of the experience.Using previous data, what can we reasonably expect from Tolicizumab?

In addition, this announcement sparked a real uproar at the AP-HP after the drafting of this article, including the resignation of the evaluation committee of this drug.The information delivered here is therefore to be taken with the greatest precaution.

What is Tolicizumab?

Tocilizumab is a recombinant humanized monoclonal antibody which acts as an interleukin receptor antagonist (IL) -6.In other words, it is a molecule that inhibits the inflammatory reaction of the body.It is mainly used and authorized in patients with rheumatoid arthritis in order to reduce the chronic overall inflammation of the body.

This medication is expensive and is difficult to produce, unlike chloroquine.But this is not a relevant criterion to judge or not its effectiveness within the COVVI-19.

The mechanisms hiding behind this therapy

The logic behind clinical trials testing tocilizumab is the reduction of the famous citokynic storm that occurs in certain patients with severe form of the disease.Indeed, in these patients seriously infected with the SARS-COV-2, sometimes falls a storm of inflammatory molecules in reaction to the infection.Epithelial cells are infected with the virus, cell permeability increases, this with the aim of fighting infection.

But, by mechanisms poorly identified again, this strategy degenerates and the immune system occurred, resulting in the failure of certain vital organs and the death of the patient.Interleukin-6, citokine inhibited by tocilizumab, would play a preponderant role in this storm.So that's why tocilizumab is tested.We hope, thanks to him, to prevent the sole -dreaded cytokine storm.

What can we expect from tocilizumab?

Small experiences have already taken place concerning tocilizumab.None of them respect the standards of clinical trials, so it is difficult to draw clinical recommendations from it.The communication of the AP-HP suggests a rigorous publication (randomized and multi-centric trial) but, for the moment, the publication is not available.It is therefore impossible to know what is worth both in terms of methodological and in terms of results.

In addition, Sanofi laboratories have communicated on current studies concerning tocilizumab and show more mixed preliminary results.Currently, around thirty clinical trials are registered concerning tocilizumab in application against COVVI19.In this story, before shouting "end of game", it will still be necessary to be cautious.