Effect of mepolizumab in airway remodeling in patients with late-onset severe asthma with an eosinophilic phenotype.

BACKGROUND

Clinical trials and real-world experience have provided evidence for the clinical benefits of mepolizumab, an anti-IL-5 biologic, in severe asthma. However, limited data exist regarding the impact of mepolizumab on airway remodeling.

OBJECTIVE

We sought to investigate the effect of mepolizumab on airway structural remodeling in patients treated for severe asthma in routine clinical care.

METHODS

The MESILICO (Efficacy of Mepolizumab in patients with latE-onset Severe eosInophiLic asthma and fIxed obstruCtiOn) study is a multicenter study involving 8 pulmonology departments in Greece. This study focused on patients who initiated mepolizumab for severe asthma with an eosinophilic phenotype and had late-onset disease with obstructive patterns (impaired reversibility). Forty-seven patients were recruited, of whom 41 were enrolled in the bronchoscopy substudy. The findings were related to clinical outcome.

RESULTS

After 12 months, mepolizumab treatment was associated with significant improvements in lung function and Asthma Control Test score, along with a significant decrease in severe exacerbation events (P < .001). Thirty-four of the 41 participants (83%) had paired biopsies for comparative analysis. There was a significant reduction from baseline in sub-basement membrane thickness, airway smooth muscle area, airway smooth muscle layer thickness, extent of epithelial damage, and number of tissue eosinophils (all P < .001). The extent of reduction in airway smooth muscle layer thickness positively correlated with the submucosal eosinophil reduction (r = 0.599; P < .001).

CONCLUSIONS

This study identified that 12 months of mepolizumab treatment in patients with late-onset severe asthma, who are also characterized by eosinophilic and impaired reversibility phenotypes, not only leads to clinical improvement but also reduces indices of airway tissue remodeling suggestive of a disease-modifying effect.