“Anti-Interleukin 5 (IL-5) and IL-5Ra Biological Drugs: Efficacy, Safety, and Future Perspectives in Severe Eosinophilic Asthma”: this is the title of the study published on 31 August on Frontiers in Medicine, which was also attended by two specialists from the Personalized Medical Centre: Asthma and Allergology of Humanitas, Dr. Francesca Puggioni, pulmonologist and Deputy Director, and Professor Giorgio Walter Canonica, Director of the Centre.

The definition of asthma has changed significantly in recent years: today asthma is no longer considered a single disease, caused by a momentary obstruction of the airways, but a heterogeneous disorder that includes different phenotypes and endotypes.


The Role of Interleukin 5

A more detailed analysis of the immunological mechanisms underlying the onset of asthma has shown that interleukin 5 (IL-5) is a key cytokine in several asthma phenotypes. In fact, it has a selective effect on eosinophils, the cells that support inflammation of the airways and worsen the symptoms of asthma and therefore the control of the disease.

In this sense, the division of bronchial asthma into two large groups based on the expression of the T helper 2 (TH2) lymphocyte genes underlying the disease, namely, TH2-high and TH2-low asthma, played a central role. This distinction has made it easier to assess the disease in terms of pathogenetic mechanisms. Eosinophilic inflammation has led researchers to intervene directly in the mechanisms of pathogenesis to better control the disease and reduce the number of exacerbations. The demonstration of a close link between eosinophils and interleukin 5 then shifted the focus to this cytokine, leading to the development of new drugs able to act directly on interleukin 5 and its α-subunit (IL-5Ra).


The new biological drugs

Recent clinical studies have paved the way for a promising new approach to severe asthma, with new biological drugs targeting interleukin 5 or its alpha-receptor subunit (IL-5Ra). In fact, standard therapy is not very effective in these patients: systemic corticosteroids only partially control the disease and have well known adverse effects and before now there was only one other biological treatment, omalizumab, on the market, active only on allergic subtypes. Analysis of the clinical trial design process reveals the importance of patient selection, taking into account both clinical data (exacerbations, lung function and quality of life) and biomarkers (eosinophils that predict therapeutic response). This is a further confirmation of how medicine must be increasingly personalized, adapting to the needs and characteristics of each individual patient.


The importance of a personalized approach

For many years, eosinophilic inflammation has been considered a predominant mechanism in the development of asthma. Interleukin 5 was evaluated as a possible therapeutic objective due to its role in the development and action of eosinophils. The results of the latest clinical trials and current use in clinical practice indicate that therapeutic success (decrease in exacerbations, hospitalizations and cyclical treatments with corticosteroids by mouth) depends significantly on the phenotyping of the patient. In the case of the new monoclonal antibody mepolizumab, the treatment candidate is the patient with severe asthma and a high number of eosinophils in the blood.

Eosinophils are currently the only suitable biomarker for these drugs and work will continue in an attempt to discover new biomarkers that allow a more personalized and precise prescription. The role of biomarkers will become crucial, leading physicians to choose the best anti-IL-5 and IL-5Ra drugs for patients.