• Andrew P Lane, Joaquim Mullol, Claire Hopkins, Wytske J Fokkens, Stella E Lee, Jerome Msihid, Scott Nash, Harry Sacks, Kinga Borsos, Siddhesh Kamat, Paul J Rowe, Yamo Deniz, and Juby A Jacob-Nara.
• Division of Rhinology, Sinus and Skull Base Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
• Curr Med Res Opin. 2024 Dec 14: 171-7.

ObjectiveLoss of sense of smell is a cardinal symptom of chronic rhinosinusitis with nasal polyps (CRSwNP) and significantly impacts health-related quality-of-life. Dupilumab significantly improved smell outcomes (loss of smell [LoS] score; University of Pennsylvania Smell Identification Test [UPSIT]) versus placebo in the phase 3 SINUS-24/-52 studies (clinicaltrials.gov, NCT02898454/NCT02912468) in patients with severe CRSwNP. This post hoc analysis investigated the effect of dupilumab on olfaction using UPSIT smell impairment categories.MethodsPatients with baseline smell impairment (UPSIT ≤34/≤33 [women/men; score range 0-40] AND LoS score ≥1 [0-3] AND smell/taste item of the 22-item Sinonasal Outcome Test >0 [SNOT-22; 0-5]) treated with dupilumab 300 mg or placebo once every 2 weeks on background intranasal corticosteroids were analyzed.ResultsOf 724 patients, 665 (91.9%) had smell impairment at baseline; most had anosmia (UPSIT 0-18) (dupilumab/placebo: 80.9%/79.8%). At week 24, the proportion of dupilumab-treated patients with anosmia decreased to 28.5%, while 14.9% achieved normosmia; most placebo-group patients (79.2%) remained anosmic and only 1.2% achieved normosmia (odds ratio = 17.3; 95% confidence interval = 5.1-59.0; p <.0001); results were similar at week 52. Improvements in Nasal Polyp Score, nasal congestion, and SNOT-22 total score were moderately correlated with improvements in UPSIT at weeks 24 and 52 (r = -.38 to -.50).ConclusionMost patients with severe CRSwNP had anosmia at baseline. Dupilumab treatment significantly improved smell versus placebo, with 14.9% achieving normosmia by week 24. There was a trend for better clinical outcomes in patients with greater smell improvement.

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