Chronic Rhinosinusitis With Nasal Polyps: The Effectiveness of Dupilumab in Mixed Endotypes

Objective: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex and heterogeneous condition. Cluster analyses identified mixed endotypes underlying CRSwNP, characterized by overlapping inflammatory markers, such as the co-expression of T2 and neutrophilic markers. The aim of this prospective observational study was to evaluate the effectiveness of dupilumab for CRSwNP in a real-life setting, comparing different nasal endotypes. Methods: Thirty-one patients with uncontrolled type 2 CRSwNP who underwent biologic therapy with dupilumab were included. Endoscopic examinations, nasal cytology, smell (Visual Analogue Scale—VAS), blood eosinophils, evaluation of quality of life (SNOT-22 questionnaire), and asthma severity (Asthma Control Test—ACT) were performed before starting the treatment (T0) and after 3 (T1), 6 (T2), and 12 months (T3). Results: A mixed endotype (neutrophil and eosinophil) was observed in 51.6% of cases at T0. An increase of neutrophil infiltrate between T0 and T3 was observed in 51.6% of patients. Such an increase could be present both in patients with a mixed endotype and pure eosinophil endotype at T0. A smaller improvement was observed for SNOT-22 physical symptoms, SNOT-22 nasal symptoms, SNOT-22 total score, and VAS for smell loss in patients with a neutrophil increase. However, such individuals had lower scores in these parameters at T0 and then reached the values of other subjects at T3. Conclusion: Dupilumab is an effective treatment also in mixed neutrophil-eosinophil endotypes. A peculiar clinical condition with fewer symptoms and better quality of life is present in patients that will have a neutrophil increase at nasal cytology during the treatment. Level of Evidence: 3.