Effectiveness of biologics for reducing occlusive mucus plugs in patients with severe asthma: a systematic review

Asthma is a heterogeneous disease characterized by chronic airway inflammation and reversible airflow obstruction. Particularly in severe asthma, airway mucus plugs can contribute to substantial and persistent airflow obstruction, despite inhaled corticosteroid and bronchodilator treatment. Consequently, it is important that clinicians assess and treat mucus plugs. Increased mucus production and airway eosinophilia caused by type 2 (T2) inflammation contributes to mucus plug formation and persistence. Several biologics are available to target T2 inflammation in asthma and studies have described their effects on airway mucus plugs using mucus plug scoring derived from computed tomography scans. However, the outcomes, designs and populations of the various studies have not been comprehensively summarized. A literature search was performed to identify primary publications examining the effects of biologics on mucus plugs in patients with moderate-to-severe asthma, organizing studies by design and study population. Three placebo-controlled randomized controlled trials (RCTs) were identified; one RCT of tezepelumab in patients across baseline blood eosinophil counts (BECs) and fractional exhaled nitric oxide (FeNO) levels and two RCTs of dupilumab in those with elevated BECs or sputum eosinophils and/or elevated FeNO levels. Across these RCTs, biologic treatment decreased mucus plug scores compared with placebo. In the tezepelumab RCT, greater effects were observed in patients with T2-high asthma, highlighting the association between mucus plugging and T2 inflammation. Among T2-high populations, effects were of a similar magnitude across biologics studied. Other biologics (benralizumab, mepolizumab, omalizumab and reslizumab) were evaluated in observational studies without a placebo control, demonstrating reductions in mucus plug scores after treatment. In several studies, decreases in mucus plugs with biologic treatment were associated with improvements in functional outcomes, including pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV1), air trapping, ventilation defects assessed by magnetic resonance imaging, asthma control and health-related quality of life. All studies showed residual plugs after biologic intervention, demonstrating a need for further understanding of how best to quantify and characterize mucus plugs to predict their response to treatment and develop optimal, individualised treatment strategies. This review highlights the relevance of assessing and targeting mucus plugs in clinical practice to help optimise patient outcomes.