Page 93 - Comprehensive treatment of patients with glucocorticoid-dependent severe asthma
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                                It is now generally accepted that severe asthma is not a single phenotype, but represents a heterogeneous mixture of syndromes in which a variety of clinical, physiological and inflammatory markers determine disease severity [1]. Over the past few years, several attempts have been made to categorize severe asthma into subphenotypes by applying unsupervised cluster analyses. The most prominent phenotype that emerged from these studies is the one characterized by airway eosinophilia despite the use of high-intensity anti- inflammatory treatment [2;3]. This refractory eosinophilic asthma phenotype represents about one third of patients with severe asthma [4] and is associated with frequent asthma exacerbations [5], fixed airflow limitation [6], air trapping [7] and nasal polyposis [8]. Patients with this phenotype require frequent bursts or even depend on daily oral corticosteroids, which leads to serious adverse effects and poor quality of life [4].
The important role of eosinophils in the pathogenesis of severe asthma was confirmed after the introduction of anti-interleukin (IL)-5 as a possible therapeutic tool in patients with refractory eosinophilic asthma [9]. IL-5 is a key factor in regulating the growth, differentiation, recruitment, activation and survival of eosinophils [9]. Two small proof-of-concept studies with the humanized monoclonal antibody mepolizumab strongly suggested that this anti-IL-5 was effective as a steroid sparing agent as well as in reducing the frequency of severe exacerbations and improving quality of life of patients with severe refractory eosinophilic asthma [10;11].
In this issue of the Lancet, Pavord and colleagues [12] provide further convincing evidence of mepolizumab being an effective, well tolerated and safe treatment in severe eosinophilic asthma. In a large randomized, placebo- controlled parallel-group (DREAM) trial, they administered three different doses of mepolizumab on a monthly basis for 12 months to 616 patients with poorly controlled asthma and evidence of eosinophilic inflammation. This resulted in an almost 50% reduction in clinically significant asthma exacerbations, emergency room visits and hospitalizations. These effects are very promising, and raise hope for many patients for whom no effective drugs without significant adverse effects are available today.
Targeting IL-5 in severe asthma
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