Tezepelumab in Adults with Severe Chronic Rhinosinusitis with Nasal Polyps.

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.).