Eosinophil Depletion with Benralizumab for Eosinophilic Esophagitis

被引：35

作者：

Rothenberg, Marc E. ^{[1
]}

Dellon, Evan S. ^{[5
]}

Collins, Margaret H. ^{[2
,3
,4
]}

Bredenoord, Albert J. ^{[6
]}

Hirano, Ikuo ^{[7
]}

Peterson, Kathryn A. ^{[8
]}

Brooks, Laura ^{[9
]}

Caldwell, Julie M. ^{[1
]}

Fjaellbrant, Harald ^{[10
]}

Grindebacke, Hanna ^{[10
]}

Ho, Calvin N. ^{[11
]}

Keith, Matthew ^{[12
]}

Mccrae, Christopher ^{[13
]}

Sinibaldi, Dominic ^{[14
,15
]}

White, Wendy I. ^{[16
]}

Datto, Catherine J. ^{[12
]}

机构：

[1] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Coll Med, Div Allergy & Immunol, Cincinnati, OH USA

[2] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Coll Med, Div Pathol, Cincinnati, OH USA

[3] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Coll Med, Dept Pediat, Cincinnati, OH USA

[4] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Coll Med, Dept Pathol & Lab Med, Cincinnati, OH USA

[5] Univ North Carolina Chapel Hill, Ctr Esophageal Dis & Swallowing, Sch Med, Div Gastroenterol & Hepatol, Chapel Hill, NC USA

[6] Amsterdam Univ Med Ctr, Dept Gastroenterol & Hepatol, Amsterdam, Netherlands

[7] Northwestern Univ, Kenneth C Griffin Esophageal Ctr, Feinberg Sch Med, Div Gastroenterol & Hepatol, Chicago, IL USA

[8] Univ Utah, Dept Internal Med, Div Gastroenterol, Salt Lake City, UT USA

[9] AstraZeneca, Late Stage Resp & Immunol, BioPharmaceut Res & Dev, Cambridge, England

[10] AstraZeneca, Late Stage Resp & Immunol, BioPharmaceut Res & Dev, Gothenburg, Sweden

[11] AstraZeneca, Patient Ctr Sci, BioPharmaceut Med Evidence, Res & Dev, Gaithersburg, MD USA

[12] AstraZeneca, Late stage Resp & Immunol, Res & Dev, Gaithersburg, MD USA

[13] AstraZeneca, Translat Sci & Expt Med, Early Resp & Immunol, Res & Dev, Gaithersburg, MD USA

[14] AstraZeneca, Res & Dev, BioPharmaceut Res & Dev, Gaithersburg, MD USA

[15] AstraZeneca, Res & Dev, Data Sci & AI, Gaithersburg, MD USA

[16] AstraZeneca, Res & Dev, Clin Pharmacol & Quantitat Pharmacol, Clin Pharmacol & Safety Sci, Gaithersburg, MD USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2024年 / 390卷 / 24期

关键词：

GENE-EXPRESSION; ADULT PATIENTS; ADOLESCENTS; BUDESONIDE; MANAGEMENT; DIAGNOSIS; CHILDREN; ANTIBODY; FEATURES;

D O I：

10.1056/NEJMoa2313318

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Benralizumab is an eosinophil-depleting anti-interleukin-5 receptor alpha 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.

引用

页码：2252 / 2263

页数：12

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