美国辛辛那提儿童医院医疗中心Marc E. Rothenberg团队研究了贝那利珠单抗治疗嗜酸性食管炎的疗效和安全性。相关论文发表在2024年6月27日出版的《新英格兰医学杂志》上。

贝那利珠单抗是一种消耗嗜酸性粒细胞的抗白细胞介素-5受体α单克隆抗体。贝那利珠单抗治疗嗜酸性食管炎的疗效和安全性尚不清楚。

在一项临床3期、多中心、双盲、随机、安慰剂对照试验中，研究组将12至65岁有症状和组织学活动性嗜酸性食管炎的患者按1:1的比例分配为每4周接受一次皮下贝那利珠单抗（30 mg）或安慰剂治疗。两个主要疗效终点是组织学缓解（每高倍视野≤6个嗜酸性粒细胞）和第24周吞咽困难症状问卷（DSQ；范围为0至84，得分越高表示吞咽困难越频繁或越严重）评分与基线相比的变化。

共有211名患者接受了随机分组：104名患者被分配接受贝那利珠单抗治疗，107名患者被指定接受安慰剂治疗。在第24周，与安慰剂相比，更多的患者对贝那利珠单抗有组织学缓解（87.4%对6.5%；差异为80.8个百分点；95%置信区间[CI]，72.9至88.8；P<0.001）。然而，两组之间DSQ评分与基线相比的变化没有显著差异（最小二乘平均值差异为3.0分；95%置信区间为-1.4至7.4；P=0.18）。嗜酸性食管炎内镜参考评分（该评分反映了内镜异常）与基线相比的变化无显著性组间差异。贝那利珠单抗组64.1%的患者和安慰剂组61.7%的患者报告了不良事件。没有患者因不良事件而停止试验。

研究结果表明，在这项涉及12至65岁嗜酸性食管炎患者的试验中，贝那利珠单抗组发生组织学缓解（每高倍视野≤6个嗜酸性粒细胞）的患者明显多于安慰剂组。然而，与安慰剂相比，贝那利珠单抗治疗并没有导致更少的严重吞咽困难症状。

附：英文原文

Title: Eosinophil Depletion with Benralizumab for Eosinophilic Esophagitis

Author: Marc E. Rothenberg, Evan S. Dellon, Margaret H. Collins, Albert J. Bredenoord, Ikuo Hirano, Kathryn A. Peterson, Laura Brooks, Julie M. Caldwell, Harald Fjllbrant, Hanna Grindebacke, Calvin N. Ho, Matthew Keith, Christopher McCrae, Dominic Sinibaldi, Wendy I. White, Catherine J. Datto

Issue&Volume: 2024-06-27

Abstract:

BACKGROUND

Benralizumab is an eosinophil-depleting anti–interleukin-5 receptor α monoclonal antibody. The efficacy and safety of benralizumab in patients with eosinophilic esophagitis are unclear.

METHODS

In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial, we assigned patients 12 to 65 years of age with symptomatic and histologically active eosinophilic esophagitis in a 1:1 ratio to receive subcutaneous benralizumab (30 mg) or placebo every 4 weeks. The two primary efficacy end points were histologic response (≤6 eosinophils per high-power field) and the change from baseline in the score on the Dysphagia Symptom Questionnaire (DSQ; range, 0 to 84, with higher scores indicating more frequent or severe dysphagia) at week 24.

RESULTS

A total of 211 patients underwent randomization: 104 were assigned to receive benralizumab, and 107 were assigned to receive placebo. At week 24, more patients had a histologic response with benralizumab than with placebo (87.4% vs. 6.5%; difference, 80.8 percentage points; 95% confidence interval [CI], 72.9 to 88.8; P<0.001). However, the change from baseline in the DSQ score did not differ significantly between the two groups (difference in least-squares means, 3.0 points; 95% CI, –1.4 to 7.4; P=0.18). There was no substantial between-group difference in the change from baseline in the Eosinophilic Esophagitis Endoscopic Reference Score, which reflects endoscopic abnormalities. Adverse events were reported in 64.1% of the patients in the benralizumab group and in 61.7% of those in the placebo group. No patients discontinued the trial because of adverse events.

CONCLUSIONS

In this trial involving patients 12 to 65 years of age with eosinophilic esophagitis, a histologic response (≤6 eosinophils per high-power field) occurred in significantly more patients in the benralizumab group than in the placebo group. However, treatment with benralizumab did not result in fewer or less severe dysphagia symptoms than placebo.

DOI: NJ202406273902409

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2313318