Evaluation of dupilumab and benralizumab on peripheral airway resistance and reactance in type 2 high severe asthma

<bold>Background:</bold> Small airway dysfunction (SAD) is common in persistent asthma and is related to poor outcomes. <bold>Methods:</bold> A post hoc analysis from two prospective phase IV trials (EudraCT 2019-003763-22 with benralizumab and EudraCT 2021-005593-25 with dupilumab) case matched for baseline SAD. 11 patients from each study (n=22) exhibited SAD defined by resistance heterogeneity between 5Hz and 20Hz (R5-R20) ≥0.10kPa/L/s, while 14 patients from each study (n=28) exhibited SAD defined by area under reactance curve (AX)≥1.0kPa/L. <bold>Results:</bold> In patients with SAD defined by R5-R20 there was treatment difference in the mean relative %improvement (95%CI) from baseline for dupilumab versus benralizumab amounting to 44.2%(2.1,86.3) p=0.04 for R5-20 and 42.6%(1.7,83.5) p=0.04 for AX (figure 1A). Differences between treatments for the patients with SAD defined by AX were 44.5%(−0.9,89.9) p=0.054 for R5-20 and 45.0%(8.7,81.3) p=0.02 for AX (figure 1B). <bold>Conclusion:</bold> Indirect evaluation demonstrated superiority of dupilumab on airway oscillometry outcomes compared to benralizumab. Figure 1 Individual data with means and 95%CI for within treatment %change at 12weeks from baseline treated with either Benra or Dupi. (A) In 22patients who were case matched for baseline R5-R20, Benra vs Dupi p<0.05 for R5-20 and AX (B) In 28 patients who were case matched for baseline, Benra vs Dupi significant p<0.05 for AX. <fig><object-id>erj;64/suppl_68/PA4810/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>