Asthma, which threatens the health of millions globally, is characterized by chronic inflammation of the airways, often followed by airway obstruction caused by mucous secretions and respiratory complications. Although traditional treatment regimens serve to manage the inflammatory reaction, the problem of excessive accumulation of mucous secretions and plugs remains an unresolved challenge. Recent research on dupilumab (a monoclonal antibody) is promising: the drug directly acts on airway obstruction caused by mucous secretions, significantly improving the outcome.
The study evaluates the effectiveness of dupilumab in reducing mucus plugs and improving lung function in patients with moderate and severe asthma (109 patients). This pathology is characterized by high levels of eosinophils and cytokines(including IL-4 and IL-13) in the systemic circulation. Dupilumab selectively binds to the common receptors of IL-4 and IL-13, thereby suppressing Type 2 inflammatory processes and the overproduction of mucus.
Mucus Plug Scoring
Mucus plug indicators are critically important for assessing the degree of airway obstruction. For this purpose, high-resolution Computed Tomography (CT) is used to assess the degree of airway blockage by mucus in 20 bronchopulmonary segments. Each segment is assigned a score of 1 (if blocked) or 0 (if patent); the final score ranges from 0 to 20. A score of 4 or more indicates a high mucus burden, which correlates closely with deteriorated lung function and severe airway obstruction in asthma patients. This score is an accurate, non-invasively obtained visual indicator of disease severity.
VESTIGE Clinical Trial Results
The VESTIGE study (Phase 4, international, randomized, placebo-controlled) aimed to quantitatively assess the mucus burden.
Reduction in Mucus Plugs: In the dupilumab group, after 24 weeks of therapy, the number of mucus plugs was significantly less compared to the placebo group. (This positive effect was visible as early as 4 weeks).
Improvement in Lung Function: This reduction directly correlated with increased airway volume and improved peripheral (distal) lung function.
Clinical Efficacy: More than 60% of participants had a high mucus plug score at baseline, indicating severe airway obstruction. Treatment with dupilumab significantly reduced the proportion of patients with a high mucus burden (from 67.2% to 32.8%), whereas this indicator remained almost unchanged in the placebo group.
Functional Indicators: Notably, in patients with the highest mucus plug scores, functional lung indicators increased the most. This included indicators such as FEV1 (Forced Expiratory Volume in 1 second), FVC (Forced Vital Capacity), and the FEV1/FVC ratio. The obtained data clearly show that freeing the airways from mucus plugs is a critical factor for restoring ventilation.
Essentially, dupilumab not only reduces the inflammatory process in the airways but also effectively fights excessive mucus secretion and plug formation. Thus, the drug simultaneously tackles the two main mechanisms that cause asthma symptoms. This dual therapeutic action reduces the frequency of exacerbations and significantly improves the quality of life for patients with asthma.
Source: ATS Journal
