The high economic cost of biologic drugs to treat severe asthma means it is critical for the most efficient drug to be used for each individual patient. Giorgio Walter Canonica of the Allergy and Respiratory Disease Clinic at the University of Genoa, Italy, and colleagues, reviewed the use of biologics to treat severe asthma, which affects only 5 to 10% of asthma sufferers, but accounts for about 50% of the social costs of the disease.
The scientific community now recognizes the existence of different endotypes of asthma. Each endotype has distinct pathophysiological mechanisms. Currently, there are three treatments approved by the American Thoracic Society (ATS)/European Respiratory Society (ERS) Task Force on Severe Asthma. They are omalizumab for patients with high serum IgE levels, oral glucocorticoids, and tiotropium.
The current focus in research is on finding therapies to treat specific components of the inflammation associated with asthma. The authors offer the examples of Th2-high and Th2-low asthma. Th2-high “is characterized by increased levels of Type 2 inflammation in the airways including eosinophilia, increased numbers of airway mast cells and overexpression of periostin,” explain the authors, adding that this type of asthma responds to treatment with inhaled corticosteroids, while Th2-low asthma does not.
Although multiple research teams are working to learn more about asthma endotypes, clinicians need more information about biomarkers in order to select the most efficient therapies. The current Global Initiative for Asthma (GINA) guidelines for treating patients with severe asthma include the use of a medium or high dose of one of several inhaled corticosteroids, and long-acting B-adrenergic bronchodilators (LABA). However, there are still patients who remain symptomatic while receiving those therapies.
The authors note that tiotropium, which they describe as “a long-acting inhaled anti-cholinergic agent,” can improve lung function in some severe asthma patients, and some research suggests that pairing a long-acting muscarinic antagonist (LAMA) with an inhaled corticosteroid can bring about improvement.
Three other therapies, montelukast, roflumilast, and bronchial thermoplasty are under investigation and the authors suggest that they each deserve further study. Additionally, research into treating severe refractory asthma through targeting specific molecular pathways with monoclonal antibodies is providing possible avenues of treatment. The authors say that “biologic treatments have shown promise in several phenotypes of severe asthma.”
Allergen immunotherapy (AIT) is an approach that does not treat the disease, but rather targets the allergen. There is debate in the research community regarding AIT, and the authors say that is the result of mode of administration. When AIT could only be administered subcutaneously, some patients had severe adverse reactions, including some fatalities. Now it can be administered sublingually, with better results. However, the authors note, “none of the trials evaluating asthma symptoms was adequately designed and reported: none of the trials had a sample size calculation and a power analysis based on asthma symptoms or pulmonary functions as a primary outcome.”
Identifying various endotypes of asthma, along with specific biomarkers for them, will allow for greater personalization of treatment. However, due to the high economic costs of these treatments, it will be increasingly critical for clinicians to know which therapies will work for each type. The full review, titled “Therapeutic Interventions in Severe Asthma”, can be found in the World Allergy Organization Journal
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