Biologicals severe chronic upper airways diseases SCUAD

Prof. Joaquim Mullol, Hospital Clínic – IDIBAPS, Barcelona, Catalonia, Spain on how biologicals can treat severe chronic upper airways diseases (SCUAD)!

Biologicals: How can they treat severe chronic upper airways diseases (SCUAD)?

Is there a genetic risk for developing severe chronic upper airways diseases?

We know, for example, that there is a genetic risk for developing allergic rhinitis. But so far we do not know if there is also a risk for rhinosinusitis severity or SCUAD.

How can biologicals help patients with severe chronic upper airways diseases (SCUAD)?

Biologicals are being investigated as part of the precision medicine concept, which is very close to the concept of personalized medicine. According to this concept biologicals are focusing on the treatment of specific phenotypes/endotypes. In respect to severe chronic upper airways diseases “phenotype” refers to any visible/clinical characteristic of the disease, while “endotype” refers to the underlying mechanisms of action of the disease. Biologicals are targeting specific molecules that are involved in those mechanisms of action of a disease.

What is the difference between biologicals and traditional therapies?

Corticosteroids, the classical treatment for sinusal inflammatory diseases, have a number of effects. Corticosteroids are acting on inflammatory cells, reducing cytokines and other inflammatory markers or respiratory mucus.

With biologicals, humanized monoclonal antibodies, we may target a specific molecule like IgE, IL-5 or IL-13 or a common receptor of the IL-4/IL-13 pathway.

Does that mean that only certain endotypes of severe chronic upper airways diseases can be treated with biologicals?

At the moment we do not exactly know which kind of patients with severe chronic upper airways diseases can benefit from biologicals, because the association between the concept of SCUAD and biologicals has not been very well established.

For example, biologicals are currently mainly used for the treatment of severe chronic rhinosinusitis, an area where the use of biologicals has been growing for the last five years and more and more biologicals are been developed.

But: Most of the studies using biologicals for the treatment of severe chronic rhinosinusitis are addressing patients who do not respond very well to corticosteroid treatment. In spite of medical treatment and sometimes even in spite of surgery, these patients remain chronic, severe, and uncontrolled. Whether those patients also fit into the definition of SCUAD has still to be researched.

Which of the many biologicals in the market can be used for treating SCUAD-patients?

First of all: The concept of biomarkers is very important for the use of biologicals. Only if we find a relevant biomarker for an endotype, we can reach our goal to use them to select a specific endotype of patients with severe chronic upper airways diseases for treatment with a specific biological.

The studies on biologicals executed so far have not used a biomarker approach when selecting patients as inclusion criteria in the clinical trials. The main objective of these studies was to find out if the respective monoclonal antibody was able to control the symptoms, severity, or quality of life of the treated patients. But: We are currently using the very same studies to find out more about the relevant biomarkers to be used in the future.

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