Abstract
Background/Objectives: Dupilumab blocks the interleukin-4 receptor alpha (IL-4Rα) subunit, thereby inhibiting IL-4- and IL-13-mediated signaling, and is an effective treatment for severe chronic rhinosinusitis with nasal polyps (CRSwNP). This study assessed clinical response and histopathological changes reflecting eosinophilic inflammation and tissue remodeling after 12 months of dupilumab therapy. Methods: This prospective pilot real-world study included 27 patients with severe CRSwNP. Paired sinonasal mucosal biopsies were obtained before treatment and after 12 months. Histopathological assessment included tissue eosinophilia, basement membrane thickness, subepithelial edema, tissue neutrophilia, and Charcot–Leyden crystals (CLCs). Clinical outcomes included Nasal Polyp Score (NPS), Sino-Nasal Outcome Test-22 (SNOT-22), and the 12-item Sniffin’ Sticks test. Results: Median NPS decreased from 6.0 [5.5–7.0] to 1.0 [1.0–1.0] (p < 0.001), SNOT-22 from 73.1 ± 15.7 to 14.9 ± 10.3 (p < 0.001), and olfactory scores increased from 2.85 ± 2.46 to 7.54 ± 3.19 (p < 0.001). Tissue eosinophils decreased from 122 [81–323] to 36 [19.5–76] cells/mm2 (p < 0.001), basement membrane thickness from 6.0 [4.15–7.5] to 4.0 [3.15–5.0] µm (p = 0.0019), and subepithelial edema from grade 2 [2–3] to 1 [1–1] (p < 0.001). Tissue neutrophil counts did not change significantly, while CLC prevalence decreased from 7/27 (25.9%) to 0/27 (0%; p = 0.0156; Holm-adjusted p = 0.0469). Conclusions: Twelve months of dupilumab therapy was associated with marked clinical improvement and significant histopathological changes in the sinonasal mucosa. These findings indicate that clinical improvement during treatment was accompanied by changes in eosinophilic inflammation and selected structural features of tissue remodeling.