Stapokibart for Severe Uncontrolled Chronic Rhinosinusitis With Nasal Polyps: The CROWNS-2 Randomized Clinical Trial.

Importance: Chronic rhinosinusitis with nasal polyps causes severe symptoms and impaired quality of life. Stapokibart is a novel monoclonal antibody that targets interleukin 4Rα.

Objective: To assess the efficacy and safety of stapokibart as an add-on treatment to intranasal corticosteroids in patients with severe uncontrolled chronic rhinosinusitis with nasal polyps.

Design, setting, and participants: From August 9, 2022, to April 28, 2023, this randomized, double-blind, phase 3 clinical trial, conducted at 51 hospitals in China, enrolled adult patients with chronic rhinosinusitis with nasal polyps who had a history of systemic corticosteroid use or sinonasal surgery and a bilateral nasal polyp score of 5 or greater (on a scale of 0-8) and a weekly mean nasal congestion score of 2 or greater (on a scale of 0-3). Eosinophilic chronic rhinosinusitis with nasal polyps was defined as blood eosinophils of 6.9% or greater (without asthma) or 3.7% or greater (with asthma) or an eosinophil count of 55 per high-power field or greater or 27% or greater in nasal polyp tissue. Patient follow-up was completed on June 25, 2024.

Interventions: Four weeks after initiation of mometasone furoate nasal spray, 100 µg in each nostril daily, patients were randomized to receive subcutaneous stapokibart, 300 mg, or placebo (1:1) every 2 weeks for 24 weeks. Both groups then received stapokibart for 28 weeks.

Main outcomes and measures: Co-primary end points were changes from baseline in nasal polyp score (meaningful change threshold [MCT] ≥1 point) and nasal congestion score (MCT ≥0.5 points) at week 24 in all patients and in the population with eosinophilia.

Results: Among 180 patients randomized, 179 (mean age, 45 [SD, 12.9] years; 61 [34.1%] women) received at least 1 treatment dose (n = 90 for stapokibart; n = 89 for placebo). In the overall population, the least-squares (LS) mean change in nasal polyp score from baseline to week 24 in the stapokibart vs placebo groups was -2.6 vs -0.3 points, respectively, (LS mean difference, -2.3; 95% CI, -2.6 to -1.9; P < .001); in the population with eosinophilia, the change was -3.0 vs -0.4 points, respectively (LS mean difference, -2.5; 95% CI, -2.9 to -2.1; P < .001). The LS mean change in nasal congestion score from baseline to week 24 in the stapokibart vs placebo groups was -1.2 vs -0.5 points, respectively, in the overall population (LS mean difference, -0.7; 95% CI, -0.9 to -0.5; P < .001) and -1.3 vs -0.5 points, respectively, in the population with eosinophilia (LS mean difference, -0.8; 95% CI, -1.0 to -0.6; P < .001). Serious adverse events were rare (2.2% in the stapokibart group vs 1.1% in the placebo group). Higher rates of arthralgia (7.8% vs 0%) and hyperuricemia (5.6% vs 1.1%) were reported with stapokibart vs placebo, respectively.

Conclusions and relevance: Among patients with severe chronic rhinosinusitis with nasal polyps treated with a daily intranasal corticosteroid, stapokibart reduced polyp size and severity of nasal symptoms at 24 weeks.

Trial registration: ClinicalTrials.gov Identifier: NCT05436275.