Treating eosinophilic exacerbations of asthma and COPD with benralizumab (ABRA): a double-blind, double-dummy, active placebo-controlled randomised trial.

Eosinophilic inflammation is a treatable trait commonly found during acute exacerbations of asthma and COPD.

嗜酸性粒细胞炎症是在哮喘和COPD急性加重期间常见的可治疗特征。

We hypothesised that for patients with eosinophilic exacerbations, a single injection of benralizumab, a humanised monoclonal antibody against interleukin-5 receptor-α, alone or in combination with prednisolone, will improve clinical outcomes compared with prednisolone, the standard of care.

我们假设对于嗜酸性粒细胞加重的患者，单次注射抗白细胞介素-5受体-α的人源化单克隆抗体benralizumab，无论是单独使用还是与泼尼松联合使用，都将改善临床结果，与泼尼松（标准治疗）相比。

Methods

The Acute exacerbations treated with BenRAlizumab trial (ABRA) was a multicentre, phase 2, double-blind, double-dummy, active placebo-controlledrandomised trial completed in the UK at Oxford University Hospitals NHS Foundation Trust and Guy's and St Thomas' NHS Foundation Trust.

急性加重治疗BenRAlizumab试验（ABRA）是一项在英国牛津大学医院NHS基金会信托和盖伊与圣托马斯NHS基金会信托完成的多中心、2期、双盲、双模拟、活性安慰剂对照的随机试验。

Patients were recruited from urgent care clinics and emergency departments of these two hospitals.

患者是从这两家医院的急诊诊所和急诊科招募的。

At the time of an acute exacerbation of asthma or COPD, adults with blood eosinophil counts of equal to or more than 300 cells per μL were randomly assigned in a 1:1:1 ratio to receive acute treatment with: prednisolone 30 mg once daily for 5 days and 100 mg benralizumab subcutaneous injection once (BENRA plus PRED group); placebo tablets once daily for 5 days and 100 mg benralizumab subcutaneous injection once (BENRA group); or prednisolone 30 mg once daily for 5 days and placebo subcutaneous injection once (PRED group).

在哮喘或慢阻肺急性加重时，血嗜酸性粒细胞计数等于或超过300个细胞/μL的成人按照1:1:1的比例随机分配接受急性治疗：每日一次口服30 mg泼尼松龙连续5天和一次100 mg贝拉利珠单抗皮下注射（BENRA加PRED组）；每日一次口服安慰剂连续5天和一次100 mg贝拉利珠单抗皮下注射（BENRA组）；或每日一次口服30 mg泼尼松龙连续5天和一次安慰剂皮下注射（PRED组）。

Randomisation was performed with a centralised interactive computer randomisation service.

随机分组是通过一个集中的交互式计算机随机分组服务进行的。

All patients and study research staff involved in data collection were masked to study blood results and treatment allocation.

所有患者和参与数据收集的研究人员对研究血液结果和治疗分配情况均不知情。

The co-primary outcomes were proportion of treatment failures over 90 days and total visual analogue scale (VAS) symptoms at day 28 in the pooled benralizumab groups compared with the prednisolone alone group and analysed in the intention-to-treatpopulation.

主要结果是90天内治疗失败的比例以及在第28天时综合视觉模拟量表（VAS）症状评分，在联合使用benralizumab的组别与仅使用泼尼松龙的组别中进行比较，并在意向治疗人群中进行分析。

The trial was registered on Clinicaltrials.govNCT04098718.

该试验已在Clinicaltrials.gov上注册，注册号为NCT04098718。

Results

Between May 13, 2021, and Feb 5, 2024, 287 patients were screened for study inclusion. 129 were excluded due to not having an exacerbation captured or not meeting the eosinophil exclusion criteria. 158 patients were randomly assigned at acute eosinophilic exacerbation of asthma or COPD where 86 (54%) patients were female and 72 (46%) were male with a mean age of 57 years (range, 18-84). 53 patients were randomly assigned to the PRED group, 53 were randomly assigned to the BENRA group, and 52 were assigned to the BENRA plus PRED treatment group.

在2021年5月13日至2024年2月5日期间，共有287名患者被纳入研究筛查。由于未记录到加重期或不符合嗜酸性粒细胞排除标准，有129名患者被排除在外。在哮喘或COPD急性嗜酸性粒细胞加重期，158名患者被随机分配，其中86名（54%）为女性，72名（46%）为男性，平均年龄为57岁（范围，18-84岁）。53名患者被随机分配到PRED组，53名被随机分配到BENRA组，52名被分配到BENRA加PRED治疗组。

At 90 days, treatment failures occurred in 39 (74%) of 53 in the PRED group, and 47 (45%) of 105 in the pooled-BENRA group (OR 0·26 [95% CI 0·13-0·56]; p=0·0005).

在90天时，PRED组中有39名（74%）的53名患者出现治疗失败，而在合并的BENRA组中有47名（45%）的105名患者出现治疗失败（OR 0·26 [95% CI 0·13-0·56]；p=0·0005）。

The 28-day total VAS mean difference was 49 mm (95% CI 14-84; p=0·0065), favouring the pooled-BENRA group.

28天总体视觉模拟评分(VAS)平均差异为49毫米(95%置信区间14-84; p=0·0065)，有利于综合BENRA组。

There were no fatal adverse events and benralizumab was well tolerated.

没有发生致命的不良事件，且benralizumab的耐受性良好。

Notably, hyperglycaemia and sinusitis or sinus infection adverse events were related to the prednisolone study drug only.

值得注意的是，高血糖和鼻窦炎或鼻窦感染不良事件仅与泼尼松研究药物有关。

interpretation

Benralizumab can be used as a treatment of acute eosinophilic exacerbations and achieves better outcomes than the current standard of care with prednisolone alone.

贝拉利单抗可用于治疗急性嗜酸性粒细胞加重，并且比当前仅使用泼尼松的标准治疗取得更好的结果。

These results offer a new way of treating eosinophilic endotypes of asthma and COPD exacerbations.

这些结果为治疗嗜酸性粒细胞哮喘和慢性阻塞性肺疾病（COPD）加重提供了新的治疗途径。

funding

AstraZeneca.

阿斯利康。