Effect of benralizumab on small airway dysfunction using functional respiratory imaging in patients with severe eosinophilic asthma

Introduction: Severe eosinophilic asthma (SEA) is known to respond favorably to benralizumab. Small airway dysfunction (SAD) is present across GINA stages and correlates with asthma severity. To date, effects of benralizumab on SAD in patients with SEA are unknown. This study aimed to detect changes in SAD after initiation of benralizumab in patients with SEA using Functional Respiratory Imaging (FRI). Methods: An open-label, single-arm trial in adult patients with SEA eligible for treatment with benralizumab was designed. Spirometry guided HRCT scans at FRC and TLC were evaluated before and after benralizumab and analyzed using computational fluid dynamics (FLUIDDA NV). Primary outcome was FRI based SAD, defined as change in specific image-based airway volume (SIV_AW). Wilcoxon signed ranks test was used. Preliminary data are reported. Results: 18 patients were included, 6 of which completed the study to date. SIV_AW (mL/L) at FRC increased from baseline (T0; 5.54; 4.73-7.09; median, IQR) to week 4 (6.34; 5,86-7.21 p=0.046) and week 12 (6.66; 4.89-7.94 p=0.028). SIV_AW at TLC increased (T0 8.11; 6.75-8.65) to week 4 (8.39, 6.86-8.94 p=0.028). Specific image-based airway resistance (SIR_AW in kPa*s) at T0 at FRC (1.26; 0.58-9.22) and TLC (0.64; 0.40-0.78) decreased at week 4 (FRC 0.54; 0.41-1.36, TLC 0.46; 0.34-0.58 p=0.028) and 12 (FRC 0.42; 0.19-4.25, TLC 0.46; 0.34-0.58 p=0.028). ACQ-6 (3.17 to 2.33) and SGRQ (67 to 55) improved (p<0.05) from T0 to week 12 as did FEV1 (1.40L (58%) to 1.72L (74%) p=0.028). Conclusion: FRI is feasible in patients with SEA and can detect improvements in SAD as early as 4 weeks after treatment initiation with benralizumab.