Influence of Multiple Prior Endoscopic Sinus Surgeries on Dupilumab Efficacy Including Smell Function in the DUPIREAL Population

Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent inflammatory condition that significantly reduces the quality of life due to nasal obstruction, loss of smell and rhinorrhea. Although endoscopic sinus surgery offers relief of symptoms and improvement of quality of life, recurrences are common and multiple surgeries are often required. The aim of this post hoc analysis is to verify the hypothesis that previous multiple surgeries may be associated with poor outcomes with dupilumab in a real-life setting in terms of quality of life, reduction in nasal polyps and improvement of olfaction. Methods: This is a post hoc analysis of the Phase IV real-life multicentre DUPIREAL study in patients with severe uncontrolled CRSwNP treated with dupilumab 300 mg every 2 weeks for 12 months. Inclusion criteria included adherence to treatment and olfactory evaluation measured by Sniffin' Sticks Identification Test 16 (SSIT-16). Statistical analyses included multivariate regression, evaluating correlations between baseline factors and poor outcomes in terms of NPS ≥ 4, SNOT-22 ≥ 30 and SSIT-16 ≤ 12. Results: Higher NPS at baseline was associated with an increased risk of NPS > 4 at 12 months, whereas a higher number of previous surgeries is associated with a higher probability of lower NPS. Notably, a greater number of previous surgeries was independently associated with incomplete recovery of smell, and surgery-naïve patients had a higher likelihood of achieving complete olfactory recovery. Dupilumab treatment led to a remarkable improvement in olfactory function, with anosmia rates decreasing from 60.2% to 3.3% after 1 year, although in our series, nearly half of the patients still exhibited residual olfactory impairment. Conclusions: This post hoc analysis highlights the efficacy of dupilumab for the treatment of CRSwNP in real life. Multivariate analysis revealed that multiple prior surgeries negatively impact outcomes with dupilumab during the first year of treatment, especially in terms of olfactory recovery.