Tezepelumab in Adults with Severe Chronic Rhinosinusitis with Nasal Polyps.

Abstract

Background: Treatment with tezepelumab has been effective for sinonasal symptoms in patients with severe, uncontrolled asthma and a history of chronic rhinosinusitis with nasal polyps, but its efficacy and safety in adults with severe, uncontrolled chronic rhinosinusitis with nasal polyps is unknown.

Methods: We randomly assigned adults with physician-diagnosed, symptomatic, severe chronic rhinosinusitis with nasal polyps to receive standard care and either tezepelumab (at a dose of 210 mg) or placebo subcutaneously every 4 weeks for 52 weeks. The coprimary end points were the changes from baseline in the total nasal-polyp score (range, 0 to 4 [for each nostril]; higher scores indicate greater severity) and the mean nasal-congestion score (range, 0 to 3; higher scores indicate greater severity) at week 52. Key secondary end points assessed in the overall population were the loss-of-smell score, the total score on the Sinonasal Outcome Test (SNOT-22; range, 0 to 110; higher scores indicate greater severity), the Lund-Mackay score (range, 0 to 24; higher scores indicate greater severity), the total symptom score (range, 0 to 24; higher scores indicate greater severity), and the first decision to treat with nasal-polyp surgery or use of systemic glucocorticoid therapy, or both, assessed in time-to-event analyses (individual and composite).

Results: In total, 203 patients were assigned to receive tezepelumab and 205 to receive placebo. At week 52, the patients who received tezepelumab had significant improvements in the total nasal-polyp score (mean difference vs. placebo, -2.07; 95% confidence interval [CI], -2.39 to -1.74) and the mean nasal-congestion score (-1.03; 95% CI, -1.20 to -0.86) (P<0.001 for both scores). Tezepelumab significantly improved the loss-of-smell score (mean difference vs. placebo, -1.00; 95% CI, -1.18 to -0.83), SNOT-22 total score (-27.26; 95% CI, -32.32 to -22.21), Lund-Mackay score (-5.72; 95% CI, -6.39 to -5.06), and total symptom score (-6.89; 95% CI, -8.02 to -5.76) (P<0.001 for all scores). Surgery for nasal polyps was indicated in significantly fewer patients in the tezepelumab group (0.5%) than in the placebo group (22.1%) (hazard ratio, 0.02; 95% CI, 0.00 to 0.09); there was significantly less use of systemic glucocorticoids with tezepelumab (5.2%) than with placebo (18.3%) (hazard ratio, 0.12; 95% CI, 0.04 to 0.27) (P<0.001 for both time-to-event analyses).

Conclusions: Tezepelumab therapy led to significantly greater reductions in the size of nasal polyps, the severity of nasal congestion and sinonasal symptoms, and the use of nasal-polyp surgery and systemic glucocorticoids than placebo in adults with severe, uncontrolled chronic rhinosinusitis with nasal polyps. (Funded by AstraZeneca and Amgen; WAYPOINT ClinicalTrials.gov number, NCT04851964.).