Recovery of Olfactory Function After Mepolizumab Treatment in Patients with Chronic Rhinosinusitis with Nasal Polyps: Influence of the Number of Surgeries

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a predominantly type 2 inflammatory disease associated with significant olfactory dysfunction. The real-life effect of mepolizumab on smell recovery and the influence of prior surgery and peripheral eosinophilia remain unclear. Objective: Our objective was to evaluate olfactory outcomes after 12 months of mepolizumab in CRSwNP and analyze the impact of previous surgeries and baseline blood eosinophilia. Methods: This was a prospective observational study including 33 consecutive CRSwNP patients treated with mepolizumab. Olfactory function was assessed using subjective measures (VAS: Visual Analogue Scale; SNOT-22: Sino-nasal outcome test, item 21) and psychophysical testing (BOT-8: Barcelona Olfactory Test, detection and identification). Nasal Polyp Score (NPS), peripheral eosinophilia, and quality of life were recorded. Patients were stratified by number of prior sinonasal surgeries. Results: Significant improvement occurred in all subjective and objective olfactory measures at 12 months (BOT-8 detection: 100% vs. 0%; identification: 71% vs. 0%; VAS: 3 vs. 10; SNOT-22 item 21: 1 vs. 5; all p < 0.05). A lower improvement occurred in patients with ≥3 prior; however, this subgroup was small (p < 0.001). Baseline blood eosinophilia was not associated with olfactory improvement. Larger baseline polyp size correlated inversely with subjective olfactory gain (r = −0.48; p = 0.03). Conclusions: Twelve months of mepolizumab improved olfactory function in CRSwNP, especially in patients with fewer prior surgeries. Olfactory dysfunction responds to multifactorial mechanisms beyond blood eosinophilia, including tissue remodeling, nostril obstruction and possible neuroinflammatory mechanisms involving central olfactory pathways, supporting psychophysical test assessment and reinforcing olfaction as a marker of therapeutic response.