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.