DOI: 10.6084/m9.figshare.27938972.v3
title: Dupilumab improves sense of smell and clinical outcomes in patients with severe chronic rhinosinusitis with nasal polyps with anosmia

description: Loss 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. Patients 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 &gt;0 [SNOT-22; 0–5]) treated with dupilumab 300 mg or placebo once every 2 weeks on background intranasal corticosteroids were analyzed. Of 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; <i>p</i> &lt;.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). Most 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. Chronic rhinosinusitis with nasal polyps (CRSwNP) is a condition that causes partial or complete blockage of the nose, making it difficult to breathe. This has a negative effect on many aspects of a person’s life, with loss of sense of smell one of the most common and troublesome symptoms. A drug called dupilumab, which is injected under the skin every other week, has been approved for use in people with CRSwNP. This article presents results from two studies where dupilumab was tested to see if it helped people with CRSwNP, including whether it could improve sense of smell. At the start of the trial, about 80% of people had completely lost their sense of smell, known as anosmia. After 24 weeks, fewer people taking dupilumab had no sense of smell (28.5%) and more had a completely normal sense of smell (14.9%) compared with people who took a placebo (79.2% had no sense of smell; 1.2% had a normal sense of smell). Smell was assessed again after 52 weeks and dupilumab continued to provide a similar benefit. Dupilumab also improved other aspects of CRSwNP, including reducing polyp size, clearing nose blockage, and improving quality-of-life. In summary, most people with CRSwNP at the start of the dupilumab studies had completely lost their sense of smell, and dupilumab improved smell for most people within 24 weeks. This shows the benefit of dupilumab in dealing with this bothersome and difficult-to-treat symptom of CRSwNP.