D1.455 - Dupilumab Efficacy in Unified Airways Disease: Pooled Analysis of Patients With Chronic Rhinosinusitis With Nasal Polyps/Allergic Fungal Rhinosinusitis With Coexisting Asthma in Ph3/4 Clinical Trials

Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) or allergic fungal rhinosinusitis (AFRS) and coexisting asthma frequently exhibit severe, persistent type 2 inflammation involving the upper and lower airways. Dupilumab targets key type 2 inflammatory pathways and has demonstrated efficacy in CRSwNP, AFRS, and asthma separately. We pooled 4 dupilumab trials to evaluate dupilumab efficacy in patients with type 2 inflammation in both upper and lower airways.

In this post hoc analysis, data from patients with both asthma and nasal polyps who received dupilumab 300 mg once every two weeks in the randomized, double-blind trials EVEREST (ph4 [NCT04998604]), SINUS 24/52 (ph3 [NCT02912468/NCT02898454]), and LIBERTY AIMS AFRS (ph3 [NCT04684524]), were pooled. Two analysis populations were defined: unified airways for CRSwNP outcomes (age 18+, bilateral polyps, coexisting asthma), and for asthma outcomes (age 18+, bilateral polyps, coexisting asthma, baseline asthma control questionnaire-5 [ACQ-5] ≥1.5). Mean (standard error of the mean [SEM]) change from baseline at Week 24 in nasal polyp score (NPS; primary endpoint in EVEREST and SINUS 24/52, secondary endpoint in LIBERTY AIMS AFRS), nasal congestion (NC), loss of smell (LoS), 22-item sinonasal outcome test (SNOT-22), pre-bronchodilator forced expiratory volume in 1 second, and ACQ-5 were assessed descriptively.

The numbers of patients randomized to dupilumab in LIBERTY AIMS AFRS, EVEREST, and pooled SINUS 24/52 were 33, 181, and 438, respectively. There were 449 and 300 patients included in the analysis for CRSwNP and asthma outcomes, respectively. In the unified airways population for CRSwNP outcomes, mean (standard deviation) baseline characteristics were: 6.09 (1.20) for NPS, 2.43 (0.60) for NC, 2.83 (0.44) for LoS, and 57.24 (20.43) for SNOT-22. Dupilumab improved CRSwNP outcomes at Week 24 with mean (SEM) change from baseline –2.21 (0.09) for NPS, –1.48 (0.04) for NC, –1.34 (0.05) for LoS, and –35.06 (1.14) for SNOT-22. Mean change from baseline for asthma outcomes also improved with dupilumab (Table).

In this pooled analysis, dupilumab improved both upper and lower airway outcomes in patients with unified airway disease. These findings support dupilumab’s efficacy in managing type 2 inflammatory diseases across the airway. Prospective validation is warranted to confirm these data.