Department of Dermatology and Venerology, Johannes Kepler University Hospital, Linz, Austria.
Institute of Allergology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Br J Dermatol. 2024 Jul 16;191(2):187-199. doi: 10.1093/bjd/ljae067.
Chronic spontaneous urticaria (CSU) is a relatively common skin disease associated with hives and angio-oedema. Eosinophils play a role in CSU pathogenesis. Benralizumab, an anti-interleukin-5 receptor-α monoclonal antibody, has been shown to induce nearly complete depletion of eosinophils.
To determine the clinical efficacy and safety of benralizumab in patients with CSU who were symptomatic despite H1 antihistamine treatment.
The 24-week, randomized, double-blind, placebo-controlled, phase IIb portion of the ARROYO trial enrolled adult patients with CSU who were currently on H1 antihistamine treatment. Patients were randomized to one of five treatment groups according to benralizumab dose and regimen for a 24-week treatment period. The primary endpoint was change from baseline in Itch Severity Score (ISS)7 at week 12. The key secondary endpoint was change from baseline in Urticaria Activity Score (UAS)7 at week 12. Additional secondary endpoints included other metrics to assess CSU at week 24, blood eosinophil levels, and pharmacokinetics and immunogenicity assessments. Exploratory subgroup analyses were conducted to explore responses according to demographics, clinical features and biomarkers. Safety was assessed in all treatment groups.
Of 155 patients, 59 were randomized to benralizumab 30 mg, 56 to benralizumab 60 mg and 40 to placebo. Baseline and disease characteristics were consistent with what was expected for patients with CSU. There were no significant differences in change from baseline in ISS7 score at week 12 between benralizumab and placebo [benralizumab 30 mg vs. placebo, least-squares mean difference -1.01, 95% confidence interval (CI) -3.28 to 1.26; benralizumab 60 mg vs. placebo, least-squares mean difference -1.79, 95% CI -4.09 to 0.50] nor in change from baseline in UAS7 score at week 12 between benralizumab and placebo (benralizumab 30 mg vs. placebo, P = 0.407; benralizumab 60 mg vs. placebo, P = 0.082). Depletion of blood eosinophil levels was observed at week 24 in patients treated with benralizumab. All other secondary endpoints and exploratory/subgroup analyses indicated no significant differences between benralizumab and placebo. Safety results were consistent with the known profile of benralizumab.
Although benralizumab resulted in near-complete depletion of blood eosinophils, there was no clinical benefit over placebo.
慢性自发性荨麻疹（CSU）是一种相对常见的皮肤疾病，其特征为荨麻疹和血管性水肿。嗜酸性粒细胞在 CSU 的发病机制中起作用。贝那鲁肽是一种抗白细胞介素-5 受体-α单克隆抗体，已被证明可诱导嗜酸性粒细胞几乎完全耗竭。
确定贝那鲁肽在接受 H1 抗组胺治疗后仍有症状的 CSU 患者中的临床疗效和安全性。
ARROYO 试验的 24 周、随机、双盲、安慰剂对照、IIb 期部分纳入了正在接受 H1 抗组胺治疗的 CSU 成年患者。根据贝那鲁肽的剂量和方案，患者被随机分为五组中的一组，进行为期 24 周的治疗。主要终点是治疗 12 周时瘙痒严重程度评分（ISS）7 的基线变化。关键次要终点是治疗 12 周时荨麻疹活动评分（UAS）7 的基线变化。其他次要终点包括第 24 周评估 CSU 的其他指标、血液嗜酸性粒细胞水平以及药代动力学和免疫原性评估。进行了探索性亚组分析，以根据人口统计学、临床特征和生物标志物探索反应。所有治疗组均进行了安全性评估。
在 155 名患者中，59 名被随机分配至贝那鲁肽 30mg 组，56 名被随机分配至贝那鲁肽 60mg 组，40 名被随机分配至安慰剂组。基线和疾病特征与 CSU 患者的预期相符。贝那鲁肽与安慰剂组在第 12 周时 ISS7 评分的基线变化无显著差异[贝那鲁肽 30mg 组与安慰剂组相比，最小二乘均数差值为-1.01，95%置信区间（CI）为-3.28 至 1.26；贝那鲁肽 60mg 组与安慰剂组相比，最小二乘均数差值为-1.79，95%CI 为-4.09 至 0.50]，第 12 周时 UAS7 评分的基线变化也无显著差异（贝那鲁肽 30mg 组与安慰剂组相比，P=0.407；贝那鲁肽 60mg 组与安慰剂组相比，P=0.082）。接受贝那鲁肽治疗的患者在第 24 周时观察到血液嗜酸性粒细胞水平下降。其他次要终点和探索性/亚组分析表明，贝那鲁肽与安慰剂之间无显著差异。安全性结果与贝那鲁肽已知的特征一致。
尽管贝那鲁肽导致血液嗜酸性粒细胞几乎完全耗竭，但与安慰剂相比没有临床获益。
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