Exhalation delivery system with fluticasone in chronic rhinosinusitis by eosinophil count and 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 the 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. End points included composite symptom score at weeks 4, 8, and 12, 22‐item Sino‐Nasal Outcome Test, and Patient Global Impression of Change at week 24. Outcomes were analyzed 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). Composite symptom score improvement with EDS‐FLU vs EDS‐placebo was observed across subgroups (least square means 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; with EOS ≥ 300 cells/µL, ‐2.48 vs ‐1.36; all P < .01). Similar results were observed for Sino‐Nasal Outcome Test‐22 and Patient Global Impression of Change. Treatment‐by‐subgroup interaction showed consistent benefits irrespective of asthma, allergy, or EOS count. CONCLUSION: These results support EDS‐FLU as an effective treatment for CRS, independent of the underlying inflammatory endotype or common comorbid conditions. Because of the limitations of this analysis, further investigation is warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03781804 and NCT03960580.