Division of Allergy and Clinical Immunology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Head & Skin, Upper Airways Research Laboratory, Faculty of Medicine, Ghent University, Ghent, Belgium; Division of Ear, Nose and Throat (ENT) Diseases, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm, Sweden.
Ann Allergy Asthma Immunol. 2021 May;126(5):584-592.e1. doi: 10.1016/j.anai.2021.01.012. Epub 2021 Jan 16.
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.
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.
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.
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.
Dupilumab improved upper and lower airway outcome measures and HRQoL in patients with severe CRSwNP and comorbid asthma and was well tolerated.
ClinicalTrials.gov Identifiers: NCT02912468 (SINUS-24) and NCT02898454 (SINUS-52).
慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）和 2 型哮喘具有相同的炎症发病机制，并且常同时发生。度普利尤单抗是一种全人源单克隆抗体，可阻断白细胞介素 4 和白细胞介素 13 的共同受体成分，这两种细胞因子是 2 型炎症的关键和中心驱动因素。
我们报告了度普利尤单抗与安慰剂在 3 期 SINUS-24（NCT02912468）和 SINUS-52（NCT02898454）研究中患有 CRSwNP 和合并哮喘的患者中的上、下呼吸道结局指标和健康相关生活质量（HRQoL）的影响。
在这些随机、双盲、安慰剂对照试验中，患者接受皮下注射度普利尤单抗 300mg（n=438）或安慰剂（n=286），每 2 周 1 次，同时使用糠酸莫米松鼻喷雾剂。报告第 24 周时上、下呼吸道结局指标的基线变化。
在随机的 724 例患者中，428 例（59.1%）患有合并哮喘。在第 24 周有哮喘的患者中，度普利尤单抗与安慰剂相比，改善了鼻息肉评分（-2.04）、患者报告的鼻塞评分（-1.04）、Lund-Mackay 计算机断层扫描评分（-6.43）、最大鼻吸气峰流速（46.15L/min）和 22 项鼻-鼻窦结局测试评分（-21.42；均 P<0.001）。用力呼气量 1 秒率和 6 项哮喘控制问卷评分也明显改善。与度普利尤单抗相比，安慰剂更常发生常见不良事件（鼻咽炎、头痛、注射部位红斑、鼻息肉恶化和哮喘）。
度普利尤单抗改善了患有严重 CRSwNP 和合并哮喘患者的上、下呼吸道结局指标和 HRQoL，且具有良好的耐受性。
ClinicalTrials.gov 标识符：NCT02912468（SINUS-24）和 NCT02898454（SINUS-52）。
