Win Ratio Analysis to Clarify Clinical Benefits: A Post Hoc Analysis of Phase 3 BOREAS and NOTUS (Two Pivotal Studies to Assess the Efficacy, Safety, and Tolerability of Dupilumab in Patients With Moderate-to-Severe COPD With Type 2 Inflammation).

Although some evaluations of composite end points consider each outcome to be of equal importance, win ratio analysis ranks outcomes by clinical severity, prioritizing more serious events that have the biggest impact on patients.

尽管一些复合终点的评估认为每个结果的重要性相等，但胜率分析根据临床严重程度对结果进行排名，优先考虑对患者影响最大的严重事件。

research_question

Does win ratio analysis, incorporating multiple clinician- and patient-relevant outcomes, show benefits for dupilumab over placebo in patients with COPD and type 2 inflammation?

胜率分析，结合了临床医生和患者相关的结果，是否显示了在患有COPD和2型炎症的患者中，与安慰剂相比，dupilumab的益处？

study_design_and_methods

BOREAS and NOTUS (Two Pivotal Studies to Assess the Efficacy, Safety, and Tolerability of Dupilumab in Patients With Moderate-to-Severe COPD With Type 2 Inflammation)-phase 3, randomized, double-masked, placebo-controlledtrials-enrolled patients with COPD, moderate-to-severe airflow limitation, and type 2 inflammation (screening blood eosinophil count ≥ 300 cells/μL) receiving inhaled triple or dual therapy (where inhaled corticosteroids were contraindicated).

BOREAS和NOTUS（两项评估dupilumab在中度至重度COPD伴有2型炎症患者中的疗效、安全性和耐受性的关键研究）-第3期、随机、双盲、安慰剂对照试验-招募了患有COPD、中度至重度气流受限和2型炎症（筛选时血嗜酸性粒细胞计数≥300细胞/μL）的患者，这些患者正在接受吸入性三联或双联治疗（吸入性皮质类固醇被禁忌使用）。

Patients were randomized to add-on dupilumab 300 mg (n = 938) every 2 weeks or matched placebo (n = 934) for 52 weeks.

患者被随机分配至每两周一次的附加 dupilumab 300 mg (n = 938) 或匹配安慰剂 (n = 934) 治疗，持续 52 周。

Win ratio analysis evaluated the relative efficacy of dupilumab vs placebo using data from the pooled intention-to-treatsafety population.

胜率分析使用来自意向治疗安全人群的汇总数据评估了 dupilumab 与安慰剂的相对疗效。

Hierarchical composite end points were occurrence of death, hospitalization, emergency department visits, exacerbations, lung function decline, symptoms, and quality of life.

层级复合终点事件包括死亡、住院、急诊就诊、加重、肺功能下降、症状和生活质量的变化。

Win ratios were calculated to quantify treatment effects and to assess differences in event occurrence and timing between treatment arms.

通过计算胜率比来量化治疗效果，并评估不同治疗组之间事件发生率和时间的差异。

Results

Dupilumab showed a higher win ratio than placebo after consideration of key end points, reinforcing its clinical benefits.

在考虑关键终点后，杜普利单抗显示出比安慰剂更高的胜率，这进一步强化了其临床益处。

Dupilumab increased the likelihood of improved clinically significant outcomes by 31% (win ratio, 1.31; 95% CI, 1.15-1.48).

杜普利单抗使临床显著改善结果的可能性增加了31%（胜率，1.31；95% 置信区间，1.15-1.48）。

For any given untied pair of dupilumab vs placebo recipients, the estimated probability of a better outcome for dupilumab recipients was 57%.

对于任何给定的未配对的 dupilumab 与安慰剂接受者，dupilumab 接受者获得更好结果的估计概率为 57%。

interpretation

Our results show that dupilumab improved patient- and clinician-important outcomes by reducing the risks of clinically significant severe outcomes, together with improving symptoms and lung function.

我们的结果显示 dupilumab 通过降低临床显著严重结果的风险，同时改善症状和肺功能，改善了患者和临床医生关注的结果。

This analysis provides meaningful insights into the value of composite end points and win ratio analysis that could guide future phase 3 trial designs.

这项分析为我们提供了关于复合终点和胜率分析价值的有意义见解，这些见解可以指导未来第三阶段试验的设计。

clinical_trial_registration

ClinicalTrials.gov; No.: NCT03930732 and NCT04456673; URL: www.

ClinicalTrials.gov; 编号: NCT03930732 和 NCT04456673; 网址: www.

clinicaltrials

gov.

5年总生存率为75%，95%置信区间为68-82%。