贝那利珠单抗治疗嗜酸性粒细胞性食管炎：嗜酸性粒细胞耗竭
Eosinophil Depletion with Benralizumab for Eosinophilic Esophagitis.
机构信息
From the Divisions of Allergy and Immunology (M.E.R., J.M.C.) and Pathology and Laboratory Medicine (M.H.C.), Department of Pediatrics, and the Department of Pathology and Laboratory Medicine (M.H.C.), University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati; the Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill (E.S.D.); the Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Amsterdam (A.J.B.); the Kenneth C. Griffin Esophageal Center, Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago (I.H.); the Division of Gastroenterology, Department of Internal Medicine, University of Utah, Salt Lake City (K.A.P.); Late-Stage Respiratory and Immunology, BioPharmaceuticals Research and Development, AstraZeneca, Cambridge, United Kingdom (L.B.); Late-Stage Respiratory and Immunology, BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden (H.F., H.G.); and Patient Centered Science, BioPharmaceuticals Medical Evidence (C.N.H.), Late-stage Respiratory and Immunology (M.K., C.J.D.) and Translational Science and Experimental Medicine, Early Respiratory and Immunology (C.M.), BioPharmaceuticals Research and Development, and Data Sciences and AI (D.S.) and Clinical Pharmacology and Quantitative Pharmacology, Clinical Pharmacology and Safety Sciences (W.I.W.), Research and Development, AstraZeneca, Gaithersburg, MD.
出版信息
N Engl J Med. 2024 Jun 27;390(24):2252-2263. doi: 10.1056/NEJMoa2313318.
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. (Funded by AstraZeneca; MESSINA ClinicalTrials.gov number, NCT04543409.).
背景
本那鲁单抗是一种耗竭嗜酸性粒细胞的抗白细胞介素-5 受体α单克隆抗体。本那鲁单抗治疗嗜酸性食管炎患者的疗效和安全性尚不清楚。
方法
在一项 3 期、多中心、双盲、随机、安慰剂对照试验中，我们将 12 至 65 岁的症状性和组织学活动性嗜酸性食管炎患者按 1:1 的比例随机分配，接受皮下注射本那鲁单抗（30mg）或安慰剂，每 4 周一次。主要疗效终点为组织学反应（每高倍视野≤6 个嗜酸性粒细胞）和基线时 Dysphagia Symptom Questionnaire（DSQ；范围 0 至 84，分数越高表示吞咽困难越频繁或越严重）评分的变化，在第 24 周评估。
结果
共有 211 名患者接受了随机分组：104 名患者接受本那鲁单抗治疗，107 名患者接受安慰剂治疗。在第 24 周时，本那鲁单抗组的组织学反应率高于安慰剂组（87.4% vs. 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，两组间 DSQ 评分的基线变化无显著差异（最小二乘均数差异，3.0 分；95%CI，-1.4 至 7.4；P=0.18）。基线时 Eosinophilic Esophagitis Endoscopic Reference Score 的变化在两组间无明显差异，该评分反映了内镜异常。本那鲁单抗组和安慰剂组分别有 64.1%和 61.7%的患者报告发生不良事件。无患者因不良事件退出试验。
结论
在这项涉及 12 至 65 岁嗜酸性食管炎患者的试验中，本那鲁单抗组患者的组织学反应（每高倍视野≤6 个嗜酸性粒细胞）发生率明显高于安慰剂组。然而，与安慰剂相比，本那鲁单抗治疗并未导致更少或更轻的吞咽困难症状。（由 AstraZeneca 资助；MESSINA ClinicalTrials.gov 编号，NCT04543409）。
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