度普利尤单抗对慢性鼻窦炎伴鼻息肉患者鼻腔通畅及鼻黏膜嗜酸性粒细胞水平的影响

Effects of Dupilumab on Nasal Patency and Nasal Mucosal Eosinophil Levels in Patients with Chronic Rhinosinusitis with Nasal Polyps

摘要:

目的：评估度普利尤单抗对中国慢性鼻窦炎伴鼻息肉(chronic rhinosinusitis with nasal polyps,CRSwNP)患者鼻腔通畅度及鼻黏膜嗜酸性粒细胞水平的影响,并探讨影响度普利尤单抗疗效的相关因素。方法：本研究为单中心、前瞻性、单臂、开放标签的真实世界研究,纳入2024年6月至2025年3月期间收治的38例难治性嗜酸性粒细胞型CRSwNP患者,给予度普利尤单抗治疗24周(600mg负荷剂量后,300mg每2周皮下注射)。主要终点为鼻息肉评分(Nasal Polyp Score,NPS)和鼻黏膜嗜酸性粒细胞计数(tissue eosinophil count,TEC)较基线的变化；次要终点包括鼻塞视觉模拟评分(Visual Analogue Scale,VAS)、鼻腔阻塞评分(Nasal Congestion Score,NC)、鼻腔鼻窦结局测试22条(Sino-Nasal Outcome Test-22,SNOT-22)、嗅觉功能(Threshold, Discrimination, Identification,TDI)及安全性评估。采用配对样本t检验或Wilcoxon符号秩检验比较治疗前后指标变化；多因素logistic回归分析疗效预测因素。结果：治疗24周后,NPS从基线(6.22±1.45)分降至(1.83±0.62)分(t=17.160,P<0.001),平均降低(4.41±1.93)分,应答率为71.05%(27/38)；鼻塞VAS评分从(7.21±1.13)分降至(2.84±1.95)分(t=11.953,P<0.001)；TEC从(42.52±18.39)个/高倍视野(HPF)降至(12.31±5.62)个/HPF,降幅达71.10%(t=9.684,P<0.001),81.58%患者TEC降至<10个/HPF；血清总IgE下降45.2%(Z=4.822,P<0.001)。多因素分析显示基线TEC水平是疗效良好的独立相关因素(OR=1.080,P=0.038)。不良事件发生率为34.21%,均为轻中度。结论 度普利尤单抗可显著改善中国CRSwNP患者鼻腔通畅度,降低鼻黏膜嗜酸性粒细胞浸润,且基线TEC水平较高的患者疗效更佳,为探索难治性ECRSwNP的精准治疗策略提供了初步的本土化证据。

Abstract:

Objective: To evaluate the effects of dupilumab on nasal patency and nasal mucosal eosinophil levels in Chinese patients with chronic rhinosinusitis with nasal polyps (CRSwNP), and to explore factors associated with treatment response. Methods: This single-center, prospective, single-arm, open-label real-world study enrolled 38 patients with refractory eosinophilic CRSwNP between June 2024 to March 2025. All patients received dupilumab for 24 weeks (600 mg loading dose followed by 300 mg subcutaneously every 2 weeks). The primary endpoints were changes from baseline in Nasal Polyp Score (NPS) and tissue eosinophil count (TEC). Secondary endpoints included Visual Analogue Scale (VAS) for nasal congestion, Nasal Congestion Score (NC), Sino-Nasal Outcome Test-22 (SNOT-22), olfactory function assessed by Threshold, Discrimination, Identification (TDI), and safety evaluation. Paired t-test or Wilcoxon signed-rank test was used to compare pre- and post-treatment changes. Multivariate logistic regression was performed to identify predictors of treatment response. Results: After 24 weeks of treatment, the Nasal Polyp Score (NPS) decreased from a baseline of 6.22±1.45 to 1.83±0.62 (t=17.160, P<0.001), with a mean reduction of 4.41±1.93 and a response rate of 71.05% (27/38). The Nasal Congestion VAS score decreased from 7.21±1.13 to 2.84±1.95 (t=11.953, P<0.001). The Total Eosinophil Count (TEC) decreased from 42.52±18.39 to 12.31±5.62 cells per high-power field (HPF), representing a 71.10% reduction (t=9.684, P<0.001), and 81.58% of patients achieved a TEC of <10 cells/HPF. Serum total IgE decreased by 45.2% (Z=4.822, P<0.001). Multivariate analysis identified baseline TEC levels as an independent factor associated with favorable efficacy (OR=1.080, P=0.038). The incidence of adverse events was 34.21%, all of which were mild to moderate in severity. Conclusion: Dupilumab significantly improves nasal patency and reduces nasal mucosal eosinophil infiltration in Chinese patients with CRSwNP, with greater efficacy observed in patients with higher baseline TEC levels. These findings provide real-world evidence supporting the precision treatment of refractory eosinophilic CRSwNP in a Chinese population.