B32-06 Changes in Mucus Density and Length Following Benralizumab Treatment of Severe Eosinophilic Asthma Observed With Functional Respiratory Imaging

Rationale Mucus plugging is a key pathophysiological feature in severe eosinophilic asthma (SEA), contributing to chronic airflow obstruction and frequent exacerbations. Eosinophilic inflammation may promote development of dense, long, and more persistent mucus plugging in the airways. In the BURAN study, benralizumab reduced mucus volume in patients with SEA. Here, we evaluated changes in mucus density and length. Methods BURAN was a multicenter, single-arm study (NCT05552508) that recruited adults with SEA inadequately controlled by inhaled corticosteroid and long-acting β2-agonist therapy. Benralizumab 30mg (SC) was given every 4 weeks for three doses. Computed tomography scans at baseline and following 13 weeks’ treatment were analysed using Functional Respiratory Imaging. Changes in average mucus plug density and length from baseline to Week 13 were assessed in patients with mucus plugs affecting ≥4 versus <4 bronchopulmonary segments at baseline, and patients with ≥1 affected segments, and in patients with mucus plug(s) at each visit and who had ≥4 or < 4 bronchopulmonary segments affected at baseline. Spearman’s correlation coefficients (rho) were calculated to assess associations between mucus density and length. Results The analysis set comprised 37 patients. At baseline, there was a strong positive correlation between mucus density and length (rho, 0.614 [95% CI, 0.358-0.785]; p < 0.0001). Mucus density decreased significantly from baseline to Week 13 in patients with mucus plug(s) in ≥ 4 bronchopulmonary segments at baseline (Fig.1A), but not those with <4 (Fig.1B). Significant decreases in mucus density were also observed in patients with mucus plug(s) at each visit and who had ≥4 bronchopulmonary segments affected at baseline (Fig.1C) but increased in those with <4 (Fig.1D). Mucus length decreased significantly in patients with mucus plug(s) in ≥ 4 bronchopulmonary segments at baseline (median 6.65mm [IQR, 5.20-7.99] vs. 5.68mm [IQR, 4.66-6.93]; p = 0.007) and those with mucus plug(s) at each visit and ≥4 bronchopulmonary segments affected at baseline (median 6.54mm [IQR, 4.99-8.13] vs. 5.76mm [IQR, 4.68-7.09]; p = 0.012). Significant decreases were observed in mucus density (median 0.58g/mL [IQR, 0.44-0.78] vs. 0.46g/mL [IQR, 0.25-0.66]; p = 0.007) and length (median 5.97mm [IQR, 4.25-7.66] vs. 4.69mm [IQR, 2.66-6.62]; p = 0.043) in patients with mucus plug(s) in ≥ 1 bronchopulmonary segments at baseline. At Week 13, a moderate positive correlation was observed between mucus density and length (rho, 0.471 [95% CI, 0.134-0.711]; p = 0.009). Conclusions Benralizumab reduced mucus density and length in patients with SEA. These findings may reflect the eosinophil-depleting effects achieved with benralizumab.