Effect of Dupilumab on Airway Inflammation in Patients With Persistent Asthma

Biologics targeting type 2 cytokines can inhibit airway inflammation and improve lung function in moderate-to-severe asthma; however, their impact on airway mucosal inflammatory cells is unclear. This study assessed the effects of dupilumab on airway mucosal and systemic inflammation, and related gene expression in patients with persistent asthma.

In the phase 2a EXPEDITION study (NCT02573233), patients aged 18-65 years were randomised to add-on dupilumab 300 mg (n = 20) or placebo (n = 22) every 2 weeks for 12 weeks. Pre- and post-treatment bronchial biopsies, bronchial brushings, bronchoalveolar lavage (BAL) fluid and blood samples were collected. Clinical and patient-reported outcomes, gene expression, type 2 biomarkers and safety outcomes were assessed.

Dupilumab versus placebo improved lung function and asthma control. No significant changes in eosinophils, mast cells or type 2 helper cells were observed in bronchial biopsies. Downregulation of M2 macrophage- and eosinophil-associated gene sets was observed in BAL and brushing samples after dupilumab. Dupilumab decreased multiple circulating type 2 biomarkers in peripheral blood (p_unadj < 0.001, p_adj < 0.01), goblet cell numbers (p_unadj = 0.0336; p_adj = 0.2554) and mucus area (p_unadj = 0.0426; p_adj = 0.2554) in bronchial biopsies versus placebo. The safety profile was consistent with the known safety profile of dupilumab.

Dupilumab improved lung function and asthma control while reducing circulating type 2 biomarkers. No measurable impact was observed on type 2-associated inflammatory cell numbers in airway bronchial biopsies; however, dupilumab modulated the expression of inflammation-associated gene sets. These findings provide cellular and molecular data that may explain dupilumab-driven mechanisms of improved lung function in patients with type 2 asthma.