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

ABSTRACT 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