Tissue eosinophilia suggests dupilumab treatment response in chronic rhinosinusitis with nasal polyps (CRSwNP)

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is predominantly driven by type 2 inflammation and frequently persists despite standard therapy. Dupilumab has proven efficacy, yet robust predictors of long-term response remain insufficiently defined. METHODS: In this monocentric, retrospective analysis, 163 adults with CRSwNP treated with dupilumab for ≥ 24 months were assessed at a tertiary referral center. Outcome parameters included nasal polyp score (NPS), sinonasal quality of life (SNOT-22), and olfactory function (SSIT). Treatment response was classified according to EUFOREA 2023 criteria. Archived polyp tissue from 72 patients obtained prior to Dupilumab treatment underwent histological reassessment, with eosinophilic infiltration quantified using absolute thresholds (Lee et al.: ≤10, 11–69, ≥ 70 eosinophils/HPF) and relative thresholds (Yang et al.: >20%). RESULTS: Dupilumab led to marked and sustained clinical improvements across the cohort (NPS − 4.6 ± 2.1; SNOT-22 − 44.1 ± 18.5; SSIT + 4.3 ± 2.9 at 24 months). Outcomes were independent of demographic factors, asthma, NERD, allergen sensitization, serum IgE, or blood eosinophils. In contrast, higher tissue eosinophilia correlated with enhanced short-term responses. Patients with > 20% eosinophils showed significantly greater SNOT-22 reduction at 12 months (p < 0.05). Stratification by ≥ 70 eosinophils/HPF and Yang’s classification (0–10, 11–69, ≥ 70) consistently showed superior trajectories in high-grade eosinophilia. EUFOREA response rates were highest in these subgroups, with no non-responders observed. CONCLUSION: Dupilumab achieved durable benefit across all patient subgroups, while elevated tissue eosinophilia predicted faster and more pronounced short-term improvements. Systematic eosinophil quantification may refine patient stratification and optimize biologic therapy allocation in CRSwNP.