The ABRA study, presented at the ERS 2024 congress, shows that benralizumab is more effective than corticosteroids in the treatment of eosinophilic asthma. We can rejoice at this therapeutic advance… but, according to Professor Colas Tcherakian, this research above all highlights the lack of compliance with basic treatment in bronchial respiratory diseases.
TRANSCRIPTION
Hello everyone, I am Professor Colas Tcherakian, pulmonologist at Foch hospital, and I wanted to report from the European Congress of Pneumology (ERS), a study called ABRA, and here I will rather use the term “ABRAcadabra” , as asthma disappears! This is a pretty impressive study on the potential effects of anti-IL-5 receptors. But first, I will provide a little context to understand the effectiveness and interest of this study.
The first thing to keep in mind is that in France there are 3.5 million patients suffering from COPD (chronic obstructive pulmonary disease), a bronchial disease which is mainly linked to tobacco but not only, and which is responsible for repeated visits to emergency rooms and hospitalizations (150,000 hospitalizations per year: this is enormous in terms of public health costs). And most of these exacerbations will be triggered by a virus which will cause inflammation to rise in the bronchi. Inflammation, with the arrival of immune cells including a cell type called eosinophils, which is very aggressive for the bronchi and will, instead of helping to get rid of the virus, worsen the situation. And there is another disease for which we find this type of inappropriate inflammation with eosinophils in the bronchi: it is asthma. Asthma remains an extremely common disease, and most of the time fortunately benign. 4 million French people are affected.
We therefore reach almost 8 million French people who carry a bronchial disease with a risk of exacerbation. For asthma, it’s 60,000 hospitalizations out of 4 million asthmatics. Ultimately, it is relatively little, but in terms of public health cost, once again, it is enormous and above all there is a risk of death which is essentially linked to the non-use of treatments which precisely target this inflammation eosinophil.
What are these treatments? These are inhaled corticosteroids. We now know that if you only take one treatment to open your bronchi (bronchodilators, the famous blue bomb), this does not treat the underlying problem which is inflammation. And we know that if you consume 3 vials of this famous blue bomb, you will most likely end up in the emergency room. And if you consume 1 per month, this time you risk dying. And this is what happens today to 500 young people per year in France, who sometimes die without even reaching the emergency room because they did not use the right treatment. And the right treatment is inhaled corticosteroids.
You will tell me, corticosteroids are scary, but this is corticosteroids inhaled. A few micrograms is a bit like putting an ointment on the skin to treat a small lesion. Here we treat the bronchi with micrograms of corticosteroids and it works. And you see that the mortality curve is completely inverse to the use of bronchodilator treatment alone. So there’s not too much discussion about whether this inflammation should be treated.
The big problem is that you have to treat this inflammation regularly and most of the time people don’t do it. Which explains that when people go to the emergency room, we will treat them temporarily and there is a big risk of returning to the emergency room later for the same thing; There is a high rate of treatment failure. This is the first point.
Today we are faced with this evidence: there is a lack of compliance with basic treatment in bronchial respiratory diseases.
The 2nd point is that each time you come to the emergency room for an exacerbation, that is to say the increase in these eosinophils in the bronchi because there is a virus or an element which triggered their arrival in the bronchi, you will have to take corticosteroids per os or cortisone, and ultimately you will end up with more harmful effects than if you had taken your inhaled treatment regularly. But that’s how it is, today we are faced with this evidence: there is a lack of compliance with basic treatment in bronchial respiratory diseases.
Based on this observation, the authors of the ABRA study decided to target this eosinophilic inflammation, that is to say to kill the eosinophils which are these inflammatory cells in the bronchi which damage them and which do not provide any effectiveness. in viral clearance most of the time. So by targeting these eosinophils, they used a molecule (benralizumab) which is injected once and which will have a very prolonged effect in the body and which will allow the eosinophils not only to be decapitated very quickly, but to not returning for many weeks. The researchers compared this to the standard treatment which is corticosteroid therapy by mouth. And they even did an arm where they gave benralizumab (this anti-IL-5 receptor that targets eosinophils) + corticosteroids, to see if that had a synergistic effect.
There is a major beneficial effect of benralizumab compared to corticosteroid therapy.
The results do not raise any questions: there is a major beneficial effect of benralizumab compared to corticosteroid therapy, with a odd ratio to 0 4, that is to say that you will have more than 70% of patients who only received corticosteroids by mouth who will return in the next 3 months, testifying moreover that we do not is not good about the fact that they do not take their basic treatment to avoid returning to the emergency room. This observation was already known; This first point highlights the failure of our traditional care.
The second thing is that effectively, when you add corticosteroids to benralizumab, it does nothing because it is really the eosinophil which is the key cell to target in these exacerbations to be maximally effective. The authors had the good idea to look at the level of eosinophils in the blood and they treated those who had levels above 300, which we know is abnormal. And that allowed them to probably be more effective. This actually makes this therapeutic option interesting.
Benralizumab is very expensive, but in return you avoid hospitalizations in patients who will not take their basic treatment which would cost less or who will be better treated than with cortisone by mouth which costs a few cents. So it’s an economic discussion that’s taking place.
On the other hand, where it is sad for us is that ultimately it also shows the incapacity for prevention. Today, we know that if asthmatic or COPD patients were compliant with their inhaled treatment, we would avoid these trips to the emergency room, largely without needing to use this molecule.
This is very good news for patients, but it highlights something that is lacking in France: therapeutic education.
So ultimately, this is very good news for patients, but it highlights something that is missing in France, which is therapeutic education, which is the possibility of taking care of the patient in a personalized way with nursing consultations. , groups where we explain why, how to take the treatment, where we check that the treatments are being taken — because there are patients who think they are taking their treatment well but who do not take it optimally with the device. This is reality. And we know that therapeutic education is a fundamental element to avoid recurrence and the appearance of these exacerbations. This is a very clear lack of investment by public authorities in therapeutic education.
We will find ourselves paying for an expensive drug for something that is avoidable, if we had invested in prevention.
Conclusion
This ABRA study is a very good study, it is a great proof of concept that by treating eosinophilic inflammation, we prevent exacerbations and that these drugs are better than corticosteroids for preventing exacerbation and less harmful in terms of side effects. But above all, this brings us back to the fact that today, we should not have to use them and that many of these exacerbations should be avoided with better compliance.
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