Exhalation Delivery System with Fluticasone in Chronic Rhinosinusitis by Eosinophil, Asthma, and Allergy Status.

BACKGROUND: Chronic rhinosinusitis (CRS) is an inflammatory disease of the nose and paranasal sinuses. Comorbid asthma, environmental allergies, and eosinophilia are associated with CRS. Exhalation delivery system with fluticasone (EDS-FLU) is approved for CRS; however, the influence of these features on treatment response remains unclear. OBJECTIVE: To evaluate whether baseline blood eosinophil (EOS) count, asthma, or allergies affect response to EDS-FLU in patients with CRS. METHODS: ReOpen1 and ReOpen2 were randomized, EDS-placebo-controlled studies. Patients with CRS were assigned (1:1:1) to EDS-FLU 186 μg, EDS-FLU 372 μg, or EDS-placebo, administered twice daily for 24 weeks. Endpoints included composite symptom score (CSS) at weeks 4, 8, and 12, 22-item Sino-Nasal Outcome Test (SNOT-22) and Patient Global Impression of Change (PGIC) at week 24. Outcomes were analysed for subgroups defined by asthma (yes/no), environmental allergy (yes/no), and EOS count (0-299 vs ≥300 cells/µL). RESULTS: Baseline characteristics were similar across groups (N=547). CSS improvement with EDS-FLU vs EDS-placebo was observed across subgroups (LS mean change at week 12 for EDS-FLU vs EDS-placebo in patients with asthma, -2.12 vs -1.36; without asthma, -2.40 vs -1.52; with allergy -2.12 vs -1.24; without allergy -2.37 vs -1.60; with EOS 0-299 cells/µL -2.11 vs -1.56; and with EOS ≥300 cells/µL -2.48 vs -1.36, respectively; all P<0.01). Similar results were observed for SNOT-22 and PGIC. Treatment-by-subgroup interaction showed consistent benefits irrespective of asthma, allergies, or EOS count. CONCLUSION: These results support EDS-FLU as an effective treatment for CRS, independent of underlying inflammatory endotype or common comorbid conditions. Due to the limitations of this analysis, further investigation is warranted. TRIAL REGISTRATION: Clinicaltrials.gov Identifiers: NCT03781804 and NCT03960580.