Tezepelumab significantly improved smell and taste scores in adults with chronic rhinosinusitis with nasal polyps over fifty-two weeks of treatment

BACKGROUND: Loss of smell is a principal symptom of chronic rhinosinusitis with nasal polyps (CRSwNP), affecting health-related quality of life and posing a safety hazard. METHODS: WAYPOINT (NCT04851964), a phase 3, multicenter trial in adults with uncontrolled CRSwNP, randomized patients 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Changes from baseline in biweekly mean Nasal Polyposis Symptom Diary (NPSD) loss of smell item, University of Pennsylvania Smell Identification Test (UPSIT), and 22-item Sino-Nasal Outcome Test (SNOT-22) loss of smell/taste item scores, as well as anosmia (UPSIT score ≤18) prevalence, were assessed over 52 weeks. RESULTS: Among 408 patients (tezepelumab [n = 203]; placebo [n = 205]), significant improvements with tezepelumab versus placebo in NPSD loss of smell item, UPSIT, and SNOT-22 loss of smell/taste item scores were seen at week 4 (least-squares mean [LSM] treatment difference [95% CI]: -0.36 [-0.46, -0.27]; 6.03 [4.72, 7.34]; and -1.01 [-1.22, -0.80], respectively) and week 52 (-1.01 [-1.18, -0.83]; 9.50 [7.84, 11.16]; and -1.90 [-2.20, -1.61]); all nominal p < 0.0001. Between-treatment differences in daily NPSD loss of smell item score were evident from day 7 (LSM treatment difference: -0.08 [95% CI: -0.15, -0.02]; nominal p < 0.01). Improvements in NPSD loss of smell, UPSIT, and SNOT-22 loss of smell/taste item scores were observed across multiple prespecified subgroups. Anosmia prevalence was lower with tezepelumab than placebo at week 4 (43.0% [n/N = 64/149] vs. 80.3% [n/N = 106/132]) and week 52 (31.5% [n/N = 47/149] vs. 75.8% [n/N = 100/132]). CONCLUSIONS: Tezepelumab provides early and sustained improvements in sense of smell among patients with uncontrolled CRSwNP.