D2.447 - Phenotyping of Chronic T2 Inflammatory Diseases of the Nose and Paranasal Sinuses and the Algorithm for Biologic Therapy Selection

Upper and lower airways form a unified system, making the integrated phenotyping of T2 inflammation essential for effective targeted therapy. 

Objective: To develop a phenotype-based algorithm for selecting biologics for chronic T2-inflammatory diseases of the nose and paranasal sinuses (T2-CIDNPS). 

A registry analysis of 139 adult patients with T2 severe asthma (SA) on targeted therapy (2020-2023) was performed. The proportion of patients with T2-CIDNPS was determined overall and for each SA phenotype: allergic SA, non-allergic eosinophilic SA, and mixed (a combination of allergic and non-allergic eosinophilic phenotypes) SA. Treatment was phenotype-guided: omalizumab for allergic SA and mixed SA; mepolizumab for non-allergic eosinophilic SA; dupilumab for mixed SA and non-allergic eosinophilic SA. 

T2-CIDNPS prevalence was 80.6% (112/139). Among patients with allergic SA 67.6% had allergic rhinitis (AR); 100% of non-allergic eosinophilic SA patients had chronic rhinosinusitis (CRS+/-polyps); 78.3% of mixed SA patients had AR+CRS+/-polyps. This allowed defining T2-CIDNPS phenotypes: allergic T2-CIDNP (AR), non-allergic eosinophilic T2-CIDNPS (CRS +/- polyps), and mixed T2-CIDNPS (AR + CRS +/- polyps). At 12 months, anti-IgE therapy reduced SNOT-22 scores in allergic T2-CIDNPS (46→25, p=0.001) and mixed T2-CIDNPS (55→38, p=0.012). Anti-IL-5 therapy improved symptoms in non-allergic eosinophilic T2-CIDNPS (60.5→19, p<0.001). Anti-IL4R therapy was effective across phenotypes: allergic T2-CIDNPS (50→25, p=0.008), non-allergic eosinophilic T2-CIDNPS (57→30, p<0.001), mixed T2-CIDNPS (49→14, p=0.046). An algorithm for selecting biologics based on T2-CIDNPS phenotype is proposed: for allergic T2-CIDNPS – omalizumab, alternative – dupilumab; for non-allergic eosinophilic T2-CIDNPS – anti-IL-5 biologics, alternative – dupilumab; for mixed T2-CIDNPS – dupilumab, alternative – omalizumab or anti-IL-5 drugs. 

The proposed approach to phenotyping T2-CIDNPS has significant practical value, facilitating the selection of first- and second-line targeted therapy for patients with T2-CIDNPS +/- SA, thereby minimizing errors in prescribing targeted therapy.