A combination corticosteroid and antihistamine targets key innate immune pathways at the nasal mucosa in allergic rhinitis

Abstract

Background: A novel formulation of azelastine hydrochloride and fluticasone propionate in a single spray has been shown to provide greater symptom relief than treatment with either compound alone in individuals with moderate / severe allergic rhinitis. The aim of this study was to characterise the effect of either intra‐nasal azelastine (Azep), fluticasone propionate (Flixonase) or a combination formula of azelastine hydrochloride and fluticasone propionate in a single spray on mucosal immune gene expression in the nose of individuals with moderate to severe AR. Method: This was a double‐blind, three‐armed parallel group study in which 48 individuals (n = 16 per group) with moderate/severe AR and sensitive to dust‐mite only or dust mite and grass allergens completed a 14‐day medication washout followed by a seven‐day treatment period. Participants completed a symptom and medication diary and the mini‐rhinoconjunctivitis quality of life (m‐RQLQ) questionnaire daily. At day 0 (pre‐treatment) and day 7 (end of treatment) participants completed the visual analogue scale (VAS) and provided a nasal lavage and blood sample. Samples were analysed with the PanCancer Immune Profiling kit (Nanostring Technologies, Seattle, USA). Results: All clinical and laboratory baseline parameters were similar in the groups with the exception of a significant difference in eosinophil counts, with the Azep group having a 50% lower eosinophil count than the Flixonase group (P = .04) but not the Dymista group. Participants in the Dymista group had the strongest statistically significant reduction in symptoms and improvement in quality of life (P < .0001). A total of 588 immune genes were expressed above background thresholds in nasal lavage samples across the three groups. Flixonase altered the expression of 148 genes significantly, compared to 56 immune genes in the Dymista group and 23 immune genes in the Azep group. Gene set analysis indicates that Flixonase altered the greatest number of pathways (n = 142 Flixonase; n = 53 for Dymista; n = 37 for Azep). Dymista significantly altered a number of innate immune pathways that were not altered by the monotherapies. Conclusion: The observation that Dymista alters innate immune pathways provides insight into potential mechanisms to explain the clinical effects observed with this combination therapy and provides potential biomarkers to target in other atopic conditions.