Department of Otorhinolaryngology-Head & Neck Surgery, University of Fukui, Fukui, Japan.
Department of Otorhinolaryngology, Jikei University School of Medicine, Tokyo, Japan.
Am J Rhinol Allergy. 2021 Nov;35(6):861-870. doi: 10.1177/19458924211009429. Epub 2021 Apr 11.
Strong eosinophil infiltration in chronic rhinosinusitis with nasal polyp (CRSwNP) is highly associated with recalcitrance and higher nasal polyp recurrence rate after surgery. The prevalence of eosinophilic CRSwNP (ECRS) is increasing in Asian countries including Japan. Benralizumab is a humanized anti-IL-5R alpha monoclonal antibody that depletes eosinophils by antibody-dependent cell-mediated cytotoxicity.
To assess the efficacy and safety of benralizumab in patients with ECRS.
This phase II, randomized, double-blind, placebo-controlled study was conducted in Japan. Patients were randomized 1:2:2 to placebo, a single administration of benralizumab 30 mg, or benralizumab 30 mg every 4 weeks (q4w) for a total of three doses. The primary endpoint was the change in nasal polyp score from baseline at Week 12.
Overall, 56 patients were enrolled (placebo, n = 11; benralizumab single dose, n = 22; benralizumab q4w, n = 23). Although the mean total nasal polyp score began to decrease after the initiation of benralizumab treatment, there were no statistically significant differences in change in nasal polyp score from baseline at Week 12 between benralizumab and placebo (placebo, -0.5 ± 0.8; benralizumab single, -0.3 ± 0.8; benralizumab q4w, -0.5 ± 1.5). Post-hoc analysis showed that the administration of benralizumab decreased nasal polyp scores ≥2 points in 42.2% of ECRS patients and that patients with high blood eosinophil levels had a greater tendency to respond to benralizumab treatment. The safety profile was similar to that in previous studies and no unexpected adverse events were noted.
Although benralizumab did not meet the primary efficacy endpoint, reductions of nasal polyp scores were seen in the benralizumab group compared with the placebo group over the whole study period, especially in patients with high levels of blood eosinophils.
慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）中嗜酸性粒细胞浸润程度高与疾病的难治性和手术后鼻息肉复发率高密切相关。嗜酸性粒细胞型 CRSwNP（ECRS）在包括日本在内的亚洲国家的患病率正在增加。贝那鲁肽是一种人源化抗白细胞介素-5 受体α单克隆抗体，通过抗体依赖性细胞介导的细胞毒性作用来消耗嗜酸性粒细胞。
评估贝那鲁肽治疗 ECRS 患者的疗效和安全性。
这是一项在日本进行的 II 期、随机、双盲、安慰剂对照研究。患者按 1:2:2 的比例随机分配至安慰剂组、贝那鲁肽 30mg 单次给药组和贝那鲁肽 30mg 每 4 周（q4w）给药组（共 3 剂）。主要终点为治疗 12 周时鼻息肉评分相对于基线的变化。
共纳入 56 例患者（安慰剂组 11 例，贝那鲁肽单次给药组 22 例，贝那鲁肽 q4w 组 23 例）。虽然贝那鲁肽治疗开始后总鼻息肉评分开始下降，但治疗 12 周时鼻息肉评分相对于基线的变化在贝那鲁肽组和安慰剂组之间无统计学差异（安慰剂组-0.5±0.8，贝那鲁肽单次给药组-0.3±0.8，贝那鲁肽 q4w 组-0.5±1.5）。事后分析显示，贝那鲁肽治疗使 42.2%的 ECRS 患者的鼻息肉评分降低≥2 分，且血嗜酸性粒细胞水平高的患者对贝那鲁肽治疗的反应倾向更大。安全性特征与既往研究相似，未观察到意外的不良事件。
尽管贝那鲁肽未达到主要疗效终点，但与安慰剂组相比，贝那鲁肽组在整个研究期间的鼻息肉评分均有所降低，尤其是在血嗜酸性粒细胞水平高的患者中。
