Type 2 inflammation biomarkers and their association with response to dupilumab in COPD (BOREAS): an analysis of a randomised, placebo-controlled, phase 3 trial.

Dupilumab reduced exacerbations in patients with COPD and type 2 inflammation in the BOREAS trial. In this post-hoc analysis, we evaluated the predictive value and longitudinal changes in type 2 inflammatory biomarkers in patients with COPD and type 2 inflammation from the BOREAS trial who received dupilumab treatment.

在BOREAS试验中，度普利尤单抗减少了COPD和2型炎症患者的急性加重。在这项事后分析中，我们评估了BOREAS试验中接受度普利尤单抗治疗的COPD和2型炎症患者的2型炎症生物标志物的预测价值和纵向变化。

Methods

BOREAS, a phase 3, multicentre, double-blind, randomised trial was conducted at 275 sites in 24 countries and included patients with COPD and type 2 inflammation (screening blood eosinophils ≥300 cells per μL).

BOREAS 是一项第 3 期、多中心、双盲、随机试验，在 24 个国家的 275 个地点进行，纳入了具有 2 型炎症（筛查时血液嗜酸性粒细胞 ≥300 个细胞/μL）的慢性阻塞性肺疾病（COPD）患者。

Patients were randomly assigned (1:1) to receive 300 mg of dupilumab every 2 weeks for 52 weeks or matching placebo.

患者按 1:1 的比例随机分配，接受每 2 周 300 mg 杜普利单抗治疗 52 周，或匹配安慰剂。

Randomisation was stratified by country and inhaled corticosteroid dose at baseline.

随机分组按国家和基线吸入性皮质类固醇剂量进行分层。

This post-hoc analysis assessed blood eosinophil counts, fractional exhaled nitric oxide (FeNO), serum eotaxin-3, total plasma immunoglobulin E (IgE), and serum pulmonary and activation-regulated chemokine (PARC) concentrations in the safety population.

这项事后分析评估了安全性人群中的血液嗜酸性粒细胞计数、呼出气一氧化氮分数（FeNO）、血清嗜酸性粒细胞趋化因子-3、总血浆免疫球蛋白E（IgE）和血清肺部和激活调节趋化因子（PARC）浓度。

The study was registered at ClinicalTrials.gov, NCT03930732 and is complete.

该研究已在ClinicalTrials.gov上注册，编号为NCT03930732，并已完成。

Results

BOREAS was conducted between April 15, 2019, and May 2, 2023, and included 939 patients with COPD and type 2 inflammation. 468 patients were randomly assigned to receive 300 mg of dupilumab every 2 weeks for 52 weeks and 471 were randomly assigned to receive matching placebo. 319 (34%) participants were female and 620 (66%) were male. 657 (70%) were former smokers and 282 (30%) were current smokers.

BOREAS研究于2019年4月15日至2023年5月2日进行，纳入了939名患有COPD和2型炎症的患者。其中468名患者被随机分配每两周接受300 mg的dupilumab治疗，持续52周；另外471名患者被随机分配接受匹配的安慰剂。共有319名（34%）参与者为女性，620名（66%）为男性。657名（70%）为前吸烟者，282名（30%）为当前吸烟者。

At week 52, greater median percentage reductions were observed in dupilumab versus placebo for most biomarkers (total IgE: -22·5% [IQR -30·4 to -16·5] vs -0·9% [-6·5 to 4·8]; FeNO: -28·6% [-57·1 to 0] vs -6·9% [-35·7 to 25·0]; eotaxin-3: -8·8% [-15·6 to -2·9] vs -0·4% [-5·6 to 5·0]; and PARC: -14·4% [-29·2 to 2·1] vs -0·8% [-13·9 to 17·2]).

在第52周时，与安慰剂相比，大多数生物标志物在dupilumab治疗组中观察到更大的中位百分比降低（总IgE：-22·5% [四分位数间距IQR -30·4至-16·5] vs -0·9% [-6·5至4·8]；FeNO：-28·6% [-57·1至0] vs -6·9% [-35·7至25·0]；eotaxin-3：-8·8% [-15·6至-2·9] vs -0·4% [-5·6至5·0]；以及PARC：-14·4% [-29·2至2·1] vs -0·8% [-13·9至17·2]）。

Reductions were similar across treatment groups by blood eosinophil counts.

通过血液嗜酸性粒细胞计数，两组治疗的降低幅度相似。

Exacerbation risk overall was reduced, with a greater magnitude of reduction in those with higher baseline blood eosinophil count (p=0·0056) and baseline FeNO (p=0·043).

总体上，恶化的风险降低了，基线血液嗜酸性粒细胞计数较高者（p=0·0056）和基线FeNO（p=0·043）的降低幅度更大。

interpretation

Patients with COPD and type 2 inflammation who were given dupilumab showed reduced type 2 inflammatory biomarkers, with elevated blood eosinophil count and FeNO predicting greater treatment response.

给予 dupilumab 的慢性阻塞性肺疾病（COPD）和2型炎症患者显示出2型炎症生物标志物降低，血液嗜酸性粒细胞计数和FeNO升高预测了更大的治疗反应。

These findings support biomarker-driven treatment strategies to optimise therapy.

这些发现支持采用生物标志物驱动的治疗策略来优化治疗。

funding

Sanofi and Regeneron Pharmaceuticals.

赛诺菲和再生元制药公司。