Page 94 - Comprehensive treatment of patients with glucocorticoid-dependent severe asthma

Chapter 5
Yet, several questions remain unanswered. The first question refers to the outcomes of the DREAM study. Similar to earlier proof-of-concept studies [10;11], mepolizumab was effective in reducing exacerbations, but failed to produce consistent improvements in symptoms or lung function. This striking dissociation between clinical and functional parameters on the one hand and exacerbations on the other hand, suggests that they represent different aspects of the disease, with different underlying pathophysiology. It is conceivable that lung function and asthma symptoms are more closely related to variations in airway calibre due to contraction of hyperresponsive airway smooth muscles, while (severe) exacerbations are elicited by flare-ups of eosinophilic inflammation in large and small airways. As a consequence, for a comprehensive treatment of patients with severe refractory eosinophilic asthma, anti-IL-5 treatment should be combined with an appropriate therapy targeting the smooth muscle.
The second question refers to the target population. To whom should mepolizumab be prescribed (or not)? From the current study it becomes evident that the best candidates for a successful treatment are asthma patients with active eosinophilic inflammation despite adequate intake of high doses of inhaled corticosteroids, in particular those with frequent exacerbations and a good response to oral corticosteroids. This excludes the prescription of anti- IL-5 to patients with other subphenotypes of severe asthma, such as the non- eosinophilic obese or beta-2-agonist dependent phenotypes [2].
Furthermore, mepolizumab can also play a role in eosinophilic diseases other than severe asthma. Patients with refractory eosinophilia represent a substantial proportion of the non-smoking patients with severe asthma, but eosinophilia is also common in patients with asthma who are (ex)smokers and in COPD patients with frequent exacerbations [13]. It might, therefore, be interesting to explore the effects of anti-IL-5 treatment in these highly prevalent patient populations as well. Another category of patients to consider are the ones with refractory eosinophilic nasal polyposis and only mild-moderate asthma. Nasal polyposis is a known risk factor of late onset asthma, and often precedes the progression to more severe forms of the disease. Anti-IL-5 treatment has been shown to significantly decrease severity scores of nasal polyps in patients refractory to corticosteroids [14], and might thereby prevent asthma from becoming become severe and corticosteroid dependent.
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