Use of tezepelumab for chronic rhinosinusitis with nasal polyps by eosinophilic endotype: WAYPOINT post-hoc analysis

The phase 3 WAYPOINT study (NCT04851964) reported that tezepelumab improved outcomes in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), including nasal polyp size, nasal congestion, and sinonasal symptoms, and reduced the need for surgery and systemic corticosteroids (SCS).

To evaluate the efficacy and safety of tezepelumab across Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis-defined eosinophilic chronic rhinosinusitis (ECRS) subgroups.

Adults with severe CRSwNP were randomized to tezepelumab 210 mg or placebo every 4 weeks. Coprimary end points were the change from baseline to week 52 in total Nasal Polyp Score and the biweekly mean Nasal Congestion Score. Secondary end points included loss of smell score, SinoNasal Outcome Test 22-item total score, Lund-Mackay total score, Nasal Polyposis Symptom Diary total symptom score, and surgery and/or SCS requirement. Safety was also assessed.

Of the 408 patients, ECRS classifications were non-ECRS (11.5%), mild (18.9%), moderate (37.0%), and severe (32.6%). Compared with placebo, tezepelumab provided greater reductions from baseline to week 52 in total Nasal Polyp Score (least squares mean difference [95% CI], -1.68 [-2.27 to -1.09] and -2.25 [-2.64 to -1.87] in the non-/mild and moderate/severe subgroups, respectively; both P < .0001) and biweekly mean Nasal Congestion Score (-0.78 [-1.11 to -0.46] and -1.15 [-1.35 to -0.94], respectively; both P < .0001). Improvements in secondary end points were also greater with tezepelumab than with placebo and were consistent across subgroups. No new safety concerns were identified.

Tezepelumab demonstrated robust efficacy across ECRS subgroups, supporting its potential as a treatment for severe CRSwNP, regardless of eosinophilic phenotype.