B78-18 Effect of Mepolizumab on CT-evaluated Mucus Burden in COPD With Eosinophilic Bronchitis

Purpose

A third of COPD patients without asthma have eosinophilic bronchitis (COPD-EB) that responds to inhaled corticosteroids.1 Anti-IL5 biologics, such as mepolizumab, have been effective in treating asthma, however their efficacy in COPD less clear. Computed tomography (CT) imaging investigations in asthma have observed improved airway mucus burden following mepolizumab treatment.2 Mucus plugging plays a key role in COPD airway obstruction and is related to mortality and exacerbation frequency.3 Therefore, we hypothesized COPD-EB patients would demonstrate mucus plugging improvements following mepolizumab treatment.

Methods

This was a retrospective analysis of 17 patients with moderate-to-severe COPD-EB (sputum eosinophils >3%) drawn from a randomized, double-blind, placebo-controlled trial (NCT01463644). Eight patients received monthly mepolizumab (750mg) infusions and 9 received placebo.4 At baseline and 6-months, all patients underwent full-inspiratory chest CT, performed spirometry, and sputum induction for cell counts. CT scans were reviewed for mucus plugs using VIDA|vision software (VIDA Diagnostics) to determine CT mucus score, reported as the number of bronchopulmonary segments with at least one plug.

Results

At baseline, CT-evidence of mucus plugging was present in 5/8 (63%) mepolizumab-treated COPD-EB patients (n = 8: 4M/4F, age=65±6 years, FEV1/FVC=60±10%) and 9/9 (100%) patients who received placebo (n = 9: 8M/1F, age=66±5 years, FEV1/FVC=50±8%). Mepolizumab reduced sputum eosinophils counts at 6-months (p = 0.007), but there was no significant CT mucus score or FEV1 change for either group (all p > 0.05). As shown in Figure 1C, all mepolizumab-treated patients with baseline mucus plugging demonstrated FEV1 improvement at 6-months /(4/5 (80%) achieved the MCID of ≥ 100mL; median change=120mL [60 to 330], p = 0.06). In contrast, mepolizumab-treated patients without mucus plugging at baseline showed no clinically meaningful improvement (0/3 (0%) achieved MCID; median change=-30mL [-40 to 30], p=.59), nor did patients who received placebo (3/9 (33%) achieved MCID; median change=50mL [-150 to 410], p = 0.43). In all participants, the change in mucus score at 6-months was significantly correlated with the change in FEV1 (Figure 1D: r=-0.72, p = 0.001).

Conclusions

Among COPD patients with eosinophilic bronchitis, only those with CT-evidence of mucus plugging demonstrated improved lung function after 6-months of mepolizumab. In patients with COPD, eosinophils in the airway associated with mucus rather than isolated eosinophilia may be a predictor to anti-IL5 therapy response. Correlations between mucus improvement and lung function indicates that COPD-EB patients may benefit from therapies that reduce mucus burden.

References:

1. D’silva et al. CanRespirJ 2011. 2. Hara et al. JAsthmaAllerg 2025. 3. Diaz et al. JAMA 2023. 4. Dasgupta et al. ERJ 2016.

This abstract is funded by: None