Research Summary

Stapokibart Reduces Polyp Burden and Symptoms in Severe Chronic Rhinosinusitis with Nasal Polyps

Kate Young

Key Highlights

  • Stapokibart significantly reduced nasal polyp size and nasal congestion scores at 24 weeks compared with placebo in patients with severe chronic rhinosinusitis with nasal polyps.
  • Improvements were seen in both the overall population and in those with eosinophilic disease.
  • Secondary outcomes, including CT scores, smell function, and quality-of-life measures, also showed marked improvement with stapokibart.
  • Stapokibart was generally well tolerated, with rare serious adverse events and manageable safety signals.

Stapokibart, a novel anti–interleukin 4Rα monoclonal antibody, demonstrated clinically meaningful efficacy in reducing nasal polyp size and alleviating nasal congestion in patients with severe chronic rhinosinusitis with nasal polyps inadequately controlled by intranasal corticosteroids. In a phase 3 randomized clinical trial conducted by Shen Shen, MS, and colleagues, stapokibart significantly improved both co–primary end points compared with placebo at 24 weeks, confirming its therapeutic role in this population.

Chronic rhinosinusitis with nasal polyps is a highly burdensome condition that affects up to 4% of individuals worldwide and is associated with impaired quality of life and high health care costs. Conventional treatment with intranasal corticosteroids is often insufficient, leaving many patients dependent on systemic corticosteroids or sinonasal surgery. Biologic therapies targeting type 2 inflammation have recently emerged as effective alternatives, with IL-4Rα blockade demonstrating particular promise, according to the researchers. Stapokibart, a novel humanized monoclonal antibody with a distinct binding epitope from dupilumab, had previously shown efficacy in phase 2 testing. This phase 3 study further evaluated its role in broader patient populations.

From August 2022 through April 2023, 180 patients from 51 centers in China were enrolled and randomized to receive stapokibart 300 mg or placebo subcutaneously every 2 weeks for 24 weeks, in addition to daily mometasone furoate nasal spray. Eligible participants had severe disease, with a bilateral nasal polyp score ≥ 5 and a nasal congestion score ≥ 2, and most had a history of systemic corticosteroid use or sinonasal surgery. Approximately 78% had eosinophilic chronic rhinosinusitis with nasal polyps, and nearly half had comorbid asthma. Patients were followed for 60 weeks, including an open-label extension phase.

At week 24, stapokibart achieved significantly greater reductions in nasal polyp score (least-squares mean change, –2.6 vs –0.3 with placebo; difference, –2.3; P < .001) and nasal congestion score (–1.2 vs –0.5; difference, –0.7; P < .001) in the overall population. Efficacy was consistent in the eosinophilic subgroup, with mean differences of –2.5 for polyp score and –0.8 for congestion. Secondary outcomes favored stapokibart, including improvements in CT imaging scores (–8.0 vs –0.1; P < .001), smell function (UPSIT score +7.5; P < .001), loss-of-smell score, and disease-specific quality of life (SNOT-22 score –23.5 vs –11.4; P < .001). Notably, 42.2% of stapokibart-treated patients were polyp free or had only small unilateral polyps at week 24 compared with 1.1% in the placebo group, and more than half had minimal or no nasal congestion. Benefits were evident as early as week 2 for polyp size and week 4 for congestion.

The safety profile was acceptable, with adverse event rates similar between stapokibart and placebo. Serious adverse events were rare (2.2% vs 1.1%), and most were not treatment related. Arthralgia (7.8%) and hyperuricemia (5.6%) occurred more frequently with stapokibart, but only one arthralgia case was considered drug related. Discontinuations due to adverse events were uncommon. Overall, stapokibart was well tolerated throughout 52 weeks of treatment.

Study limitations include the lack of evaluation of aspirin-exacerbated respiratory disease, limited statistical power for patients without eosinophilia, and enrollment restricted to a Chinese population, which may affect generalizability.

“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,” Shen and colleagues concluded.

Reference:
Shen S, Yan B, Wang M, et al. Stapokibart for severe uncontrolled chronic rhinosinusitis with nasal polyps: the crowns-2 randomized clinical trial. JAMA. Published online August 18, 2025. doi:10.1001/jama.2025.12515