Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) and type 2 asthma share the same inflammatory pathophysiology and are frequent comorbidities. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin 4 and interleukin 13, which are key and central drivers of type 2 inflammation.

Objective

We report the effect of dupilumab vs placebo on outcome measures of the upper and lower airways and health-related quality of life (HRQoL) in the pooled population of patients with CRSwNP and comorbid asthma from the phase 3 SINUS-24 (NCT02912468) and SINUS-52 (NCT02898454) studies.

Methods

In these randomized, double-blind, placebo-controlled trials, patients received subcutaneous dupilumab 300 mg (n = 438) or placebo (n = 286) every 2 weeks on a background of mometasone furoate nasal spray. Changes from baseline at week 24 in the upper and lower airway outcome measures are reported.

Results

Of the 724 patients randomized, 428 (59.1%) had comorbid asthma. In patients with asthma at week 24, dupilumab vs placebo improved the nasal polyp score (−2.04), patient-reported nasal congestion score (−1.04), Lund-Mackay computed tomography scan score (−6.43), peak nasal inspiratory flow (46.15 L/min), and 22-item sinonasal outcome test score (−21.42; all P < .001). The forced expiratory volume in 1 second and 6-item asthma control questionnaire scores were also markedly improved with dupilumab vs placebo. The most common adverse events (nasopharyngitis, headache, injection-site erythema, worsening of nasal polyposis, and asthma) were more frequent with placebo than dupilumab.

Conclusion

Dupilumab improved upper and lower airway outcome measures and HRQoL in patients with severe CRSwNP and comorbid asthma and was well tolerated.

Trial Registration

ClinicalTrials.gov Identifiers: NCT02912468 (SINUS-24) and NCT02898454 (SINUS-52).

中文翻译：

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Dupilumab可改善慢性鼻-鼻窦炎伴鼻息肉和哮喘的上，下呼吸道疾病控制

背景

慢性鼻鼻窦炎伴鼻息肉（CRSwNP）和2型哮喘具有相同的炎症病理生理学，是常见的合并症。Dupilumab是一种完全的人类单克隆抗体，可阻断白细胞介素4和白介素13的共享受体成分，白细胞介素4和白细胞介素13是2型炎症的关键和主要驱动因素。

客观的

我们报告了dupilumab vs安慰剂对3期SINUS-24（NCT02912468）和SINUS合并CRSwNP和合并症的患者的上，下呼吸道结局指标和健康相关生活质量（HRQoL）的影响-52（NCT02898454）研究。

方法

在这些随机，双盲，安慰剂对照试验中，患者每隔2周接受糠酸莫米松鼻喷雾剂皮下注射dupilumab 300 mg（n = 438）或安慰剂（n = 286）。报告了上，下气道预后指标在第24周时相对于基线的变化。

结果

在随机分配的724名患者中，有428名（59.1％）患有合并症。在第24周患有哮喘的患者中，dupilumab vs安慰剂可改善鼻息肉评分（−2.04），患者报告的鼻充血评分（−1.04），Lund-Mackay CT扫描评分（−6.43），鼻吸气流量峰值（46.15）。 L / min）和22项鼻窦结果测试得分（−21.42;所有P <.001）。dupilumab与安慰剂相比，在1秒和6项哮喘控制问卷得分中的强制呼气量也显着改善。与安慰剂相比，安慰剂最常见的不良事件（鼻咽炎，头痛，注射部位红斑，鼻息肉恶化和哮喘）更为频繁。

结论

患有严重CRSwNP和合并症的哮喘患者，Dupilumab改善了上，下气道预后指标和HRQoL，并且耐受性良好。

试用注册

ClinicalTrials.gov标识符：NCT02912468（SINUS-24）和NCT02898454（SINUS-52）。