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. (Funded by AstraZeneca; MESSINA ClinicalTrials.gov number, NCT04543409.).
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.).
摘要：
背景：Benralizumab是一种嗜酸性粒细胞消耗性抗白介素-5受体α单克隆抗体。贝那利珠单抗治疗嗜酸性粒细胞性食管炎的疗效和安全性尚不清楚。
方法：在第三阶段，多中心，双盲,随机化，安慰剂对照试验,我们将12~65岁有症状和组织学活动性嗜酸细胞性食管炎的患者按1∶1的比例进行分组,每4周接受一次贝那利珠单抗(30mg)皮下治疗或安慰剂治疗.两个主要疗效终点是组织学反应（每个高倍视野≤6个嗜酸性粒细胞）和吞咽困难症状问卷评分相对于基线的变化（DSQ;范围，0至84，较高的分数表明在第24周出现更频繁或更严重的吞咽困难）。
结果：共有211例患者接受随机分组：104例患者接受贝那利珠单抗治疗，107人被分配接受安慰剂。在第24周，使用贝那利珠单抗的组织学反应患者多于安慰剂（87.4％vs.6.5%；差异，80.8个百分点；95%置信区间[CI]，72.9至88.8；P<0.001）。然而,DSQ评分相对于基线的变化在两组之间没有显着差异（最小二乘均值的差异，3.0分；95%CI，-1.4至7.4；P=0.18）。嗜酸细胞性食管炎内镜参考评分与基线相比无明显组间差异,这反映了内窥镜异常。贝那利珠单抗组中64.1%的患者和安慰剂组中61.7%的患者报告了不良事件。没有患者因为不良事件而中止试验。
结论：在这项涉及12至65岁嗜酸性粒细胞性食管炎患者的试验中，与安慰剂组相比,贝那利珠单抗组出现组织学缓解(每个高倍视野≤6个嗜酸性粒细胞)的患者明显更多.然而,贝那利珠单抗治疗未导致比安慰剂更少或更不严重的吞咽困难症状.（由阿斯利康资助；MESSINAClinicalTrials.gov编号，NCT04543409。).
方法：在第三阶段，多中心，双盲,随机化，安慰剂对照试验,我们将12~65岁有症状和组织学活动性嗜酸细胞性食管炎的患者按1∶1的比例进行分组,每4周接受一次贝那利珠单抗(30mg)皮下治疗或安慰剂治疗.两个主要疗效终点是组织学反应（每个高倍视野≤6个嗜酸性粒细胞）和吞咽困难症状问卷评分相对于基线的变化（DSQ;范围，0至84，较高的分数表明在第24周出现更频繁或更严重的吞咽困难）。
结果：共有211例患者接受随机分组：104例患者接受贝那利珠单抗治疗，107人被分配接受安慰剂。在第24周，使用贝那利珠单抗的组织学反应患者多于安慰剂（87.4％vs.6.5%；差异，80.8个百分点；95%置信区间[CI]，72.9至88.8；P<0.001）。然而,DSQ评分相对于基线的变化在两组之间没有显着差异（最小二乘均值的差异，3.0分；95%CI，-1.4至7.4；P=0.18）。嗜酸细胞性食管炎内镜参考评分与基线相比无明显组间差异,这反映了内窥镜异常。贝那利珠单抗组中64.1%的患者和安慰剂组中61.7%的患者报告了不良事件。没有患者因为不良事件而中止试验。
结论：在这项涉及12至65岁嗜酸性粒细胞性食管炎患者的试验中，与安慰剂组相比,贝那利珠单抗组出现组织学缓解(每个高倍视野≤6个嗜酸性粒细胞)的患者明显更多.然而,贝那利珠单抗治疗未导致比安慰剂更少或更不严重的吞咽困难症状.（由阿斯利康资助；MESSINAClinicalTrials.gov编号，NCT04543409。).
