The effect of dupilumab on lung function parameters in patients with oral corticosteroid-dependent severe asthma

Abstract

Background

In Phase 3 LIBERTY ASTHMA VENTURE (NCT02528214), add-on dupilumab reduced oral corticosteroid (OCS) use while reducing severe exacerbations and improving pre-bronchodilator (BD) forced expiratory volume in 1 s (FEV₁) in OCS-dependent severe asthma patients.

Objective

This post hoc study evaluated dupilumab's efficacy based on several lung function parameters for the overall population and subgroups defined by baseline biomarkers.

Methods

Lung function parameters were pre- and post-BD FEV₁, pre-BD forced vital capacity (FVC), FEV₁/FVC, and forced expiratory flow 25–75% (FEF_25–75%). Dupilumab's steroid-sparing efficacy according to FEV₁ improvement (≥ 200 mL vs < 200 mL) or in patients with 0 exacerbations was also assessed.

Results

At Week 24 in the overall population, pre- and post-BD FEV₁ had improved by 0.22 L (95% CI 0.09–0.34; p = 0.0007) and 0.19 L (95% CI 0.08–0.30; p = 0.0009) vs placebo, respectively; FVC by 0.27 L (95% CI 0.13–0.41; p = 0.0003); FEV₁/FVC by 1.90% (95% CI -0.26–4.07; p = 0.08); and FEF_25–75% by 0.15 L/s (95% CI 0.02–0.28; p = 0.02). Improvements were early and generally sustained over 24-weeks’ treatment. Improvements were observed regardless of baseline eosinophils or FeNO and were generally greatest in patients with eosinophils ≥ 300 cells/μL. Significant steroid-sparing effects were observed with dupilumab irrespective of FEV₁ improvement, and in exacerbation-free patients.

Conclusions

Dupilumab rapidly improved various lung function measures regardless of baseline biomarkers in OCS-dependent severe asthma patients. It showed steroid-sparing effects regardless of FEV₁ improvement, and in exacerbation-free patients. This population appears to be highly skewed toward type 2 inflammation.