Dupilumab Reduces Mucus Radiodensity and New Plug Formation in Asthma.

Abstract

Dupilumab, an interleukin (IL)-4 and IL-13 antagonist, reduces the burden of mucus plugs visualized by computed tomography (CT) in asthma. Does dupilumab modify the volume, radiodensity, and temporospatial behaviour of individual CT-visible mucus plugs in patients with moderate-to-severe asthma? Thirty-two adults with moderate-to-severe asthma were evaluated; 22 received dupilumab every 2-weeks for at-least 16-weeks, and 10 were in the control group. All mucus plugs visible on CT scans acquired at baseline and follow-up were annotated to evaluate plug count, volume, and radiodensity. Individual plugs were assessed longitudinally and classified as resolved, fixed-location persistent (FLP), or new-onset. Post-dupilumab reductions in mucus score, total mucus plug count, and total plug volume were greater than control and associated with improved FEV₁, FEV₁/FVC, and ¹²⁹Xe magnetic resonance imaging ventilation defect percent (VDP) (all p<0.05). 36% of dupilumab-treated participants had complete resolution (control: 10%) and 59% had incomplete resolution of mucus plugs (control: 80%). Compared to control, dupilumab-treated participants had more resolved (91% vs. 58%, p<0.0001), and fewer FLPs (9% vs. 42%, p<0.0001) and new-onset plugs (1[0-5] vs. 6[0-18], p=0.0008). Radiodensity of FLPs decreased post-dupilumab (-422HU [-759-(-5)] to -569HU [-738-(-258)], p=0.009), and new-onset plugs had lower radiodensity in dupilumab-treated participants compared to control (-573HU [-765-(-320)] vs. -387HU [-662-(-26)], p=0.0006). Participants with incomplete resolution had persistently higher VDP compared to those with complete resolution (p<0.05). Dupilumab reduces mucus burden in asthma by resolving persistent plugs and decreasing the formation of new plugs. Despite complete resolution in a subset of participants, residual low-radiodensity persistent and new-onset plugs are functionally relevant.