Tezepelumab Reduced Polyp Burden in Severe CrSwNP Trial

Key Takeaways

• Both coprimary week-52 endpoints favored tezepelumab over placebo in adults with severe chronic rhinosinusitis with nasal polyps.
• Loss-of-smell, SNOT-22, Lund–Mackay, and total symptom measures also favored tezepelumab.
• Tezepelumab was associated with fewer indications for nasal-polyp surgery and less systemic glucocorticoid use over 52 weeks.

In adults with severe, uncontrolled chronic rhinosinusitis with nasal polyps, tezepelumab added to standard care outperformed placebo plus standard care at 52 weeks, with a more than 2-point advantage in total nasal-polyp score. In the phase 3 WAYPOINT trial, adults with physician-diagnosed, symptomatic, severe chronic rhinosinusitis with nasal polyps received tezepelumab or placebo on top of standard care. The randomized phase 3 trial focused on week-52 efficacy after a full year of treatment. Across prespecified outcomes, differences at week 52 favored tezepelumab.

Investigators assigned 203 patients to tezepelumab and 205 to placebo, with standard care in both groups throughout the trial. Participants were adults with physician-diagnosed, symptomatic, severe chronic rhinosinusitis with nasal polyps, described in the trial as having severe, uncontrolled disease. Tezepelumab was administered at 210 mg subcutaneously every 4 weeks for 52 weeks. Coprimary endpoints were change from baseline in total nasal-polyp score and mean nasal-congestion score at week 52.

At week 52, the mean difference versus placebo in total nasal-polyp score was -2.08 (95% CI, -2.40 to -1.76; P<0.001). The mean difference in mean nasal-congestion score was -1.04 (95% CI, -1.21 to -0.87; P<0.001). Secondary outcomes moved in the same direction, with a -1.01 difference in loss-of-smell score (95% CI, -1.18 to -0.83) and a -27.44 difference in SNOT-22 total score (95% CI, -32.51 to -22.37). Lund–Mackay score differed by -5.70 (95% CI, -6.37 to -5.03), and total symptom score differed by -6.96 (95% CI, -8.09 to -5.83); all secondary comparisons had P<0.001. Symptom, imaging, and patient-reported measures also favored tezepelumab.

Time-to-event analyses showed fewer indications for nasal-polyp surgery with tezepelumab than with placebo, at 0.5% versus 22.0% (hazard ratio, 0.02; 95% CI, 0.00 to 0.09; P<0.001). Systemic glucocorticoids were used in 5.2% and 19.3%, respectively (hazard ratio, 0.11; 95% CI, 0.04 to 0.25; P<0.001).