Impact of dupilumab on SNOT-22 domains: focus on the ear

BACKGROUND: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is frequently associated with otologic symptoms due to eustachian tube dysfunction. However, the clinical relevance of otologic symptoms in patients with CRSwNP and response to biologic therapy remains poorly characterised. OBJECTIVE: To investigate baseline determinants of ear related symptoms and evaluate the impact of dupilumab treatment. METHODS: This post-hoc analysis of the DISA study included 23 adults with CRSwNP and severe uncontrolled asthma. Participants underwent a 12 week treatment with dupilumab followed by a 12 week washout period. Symptom burden was assessed using the 22 item Sino-nasal Outcome Test (SNOT-22), including domain specific analyses. Correlations between the ear and face domains as well as endoscopic nasal polyp score (NPS), peak nasal inspiratory flow (PNIF) and type 2 biomarkers were examined. RESULTS: At baseline, ear/face symptoms were common, with ear fullness representing the principal complaint. At baseline the ear/face domain correlated with other SNOT-22 domains and patient reported outcomes, but not with NPS, PNIF, or type 2 biomarkers. In response to dupilumab all SNOT-22 domains improved (p<0.001), including ear related symptoms. There was a disconnect in terms of improvements in the ear/face domain being associated with nasal symptoms, but not with NPS, PNIF or type 2 biomarkers. During washout, symptom deterioration was observed across all SNOT-22 domains. CONCLUSION: Ear related symptoms are common in CRSwNP and more closely reflect the overall quality of life burden than the degree of nasal airway obstruction as NPS and PNIF, or type 2 biomarkers. Improvements with dupilumab significantly improved these symptoms, with relapse following washout suggesting a link to type 2 inflammation. These findings support otologic symptoms are important in CRSwNP assessment and management.