Allergy and Asthma Specialists Medical Group and Research Center, Huntington Beach, Calif.
Division of Allergy and Immunology, National Jewish Health, University of Colorado, Denver, Colo.
J Allergy Clin Immunol. 2018 Jul;142(1):171-177.e1. doi: 10.1016/j.jaci.2017.11.051. Epub 2018 Jan 31.
Dupilumab, an anti-IL-4 receptor α mAb, inhibits IL-4/IL-13 signaling, key drivers of type 2/T2 immune diseases (eg, atopic/allergic disease). In a pivotal, phase 2b study (NCT01854047), dupilumab reduced severe exacerbations, improved lung function and quality of life, and was generally well tolerated in patients with uncontrolled persistent asthma despite using medium-to-high-dose inhaled corticosteroids plus long-acting β2-agonists.
To examine dupilumab's effect on the 22-item Sino-Nasal Outcome Test (SNOT-22) total score and its allergic rhinitis (AR)-associated items in asthma patients with comorbid perennial allergic rhinitis (PAR).
A post hoc analysis reporting data from the phase 2b study for the 200 and 300 mg every 2 week (q2w) doses under investigation in phase 3 (NCT02414854) was carried out. PAR was defined at study entry as a specific response to typical perennial antigens (IgE ≥0.35 Ku/L).
Overall, 241 (61%) patients had PAR. In asthma patients with PAR, dupilumab 300 mg q2w versus placebo significantly improved SNOT-22 total score (least squares mean difference, -5.98; 95% CI, -10.45 to -1.51; P = .009) and all 4 AR-associated symptoms evaluated (nasal blockage, -0.60; 95% CI, -0.96 to -0.25; runny nose, -0.67; 95% CI, -1.04 to -0.31; sneezing, -0.55; 95% CI, -0.89 to -0.21; postnasal discharge, -0.49; 95% CI, -0.83 to -0.16; all P < .01). Dupilumab 200 mg q2w demonstrated numerical, but not statistically significant, decreases in SNOT-22 total score (-1.82; 95% CI, -6.46 to 2.83; P = .443 vs placebo) and in each AR-associated symptom. In patients without PAR, no differences were observed for these measures versus placebo.
Dupilumab 300 mg q2w significantly improved AR-associated nasal symptoms in patients with uncontrolled persistent asthma and comorbid PAR.
Dupilumab 是一种抗 IL-4 受体 α mAb，可抑制 IL-4/IL-13 信号转导，这是 2 型/T2 免疫疾病（例如特应性/过敏性疾病）的关键驱动因素。在一项关键性、2b 期研究（NCT01854047）中，dupilumab 减少了重度恶化，改善了肺功能和生活质量，并且在使用中至高剂量吸入皮质激素加长效β2-激动剂治疗的情况下仍能耐受，患者存在未控制的持续性哮喘。
研究 dupilumab 对伴有常年性变应性鼻炎（PAR）的哮喘患者的 22 项 Sino-Nasal Outcome Test（SNOT-22）总评分及其与变应性鼻炎相关的项目的影响。
对正在进行的 3 期（NCT02414854）研究中研究的 200 和 300mg 每 2 周（q2w）剂量进行了 2b 期研究的事后分析报告。在研究入组时，PAR 定义为对典型常年抗原的特异性反应（IgE≥0.35Ku/L）。
总体而言，241 名（61%）患者患有 PAR。在患有 PAR 的哮喘患者中，dupilumab 300mg q2w 与安慰剂相比，SNOT-22 总评分显著改善（最小二乘均值差，-5.98；95%CI，-10.45 至-1.51；P=0.009），并且所有 4 项与变应性鼻炎相关的症状均得到改善（鼻塞，-0.60；95%CI，-0.96 至-0.25；流涕，-0.67；95%CI，-1.04 至-0.31；打喷嚏，-0.55；95%CI，-0.89 至-0.21；鼻后滴注，-0.49；95%CI，-0.83 至-0.16；均 P<0.01）。dupilumab 200mg q2w 显示 SNOT-22 总评分（-1.82；95%CI，-6.46 至 2.83；P=0.443 与安慰剂）和每个与变应性鼻炎相关的症状均有数值上但无统计学意义的降低。在没有 PAR 的患者中，与安慰剂相比，这些措施没有差异。
dupilumab 300mg q2w 可显著改善伴有未控制的持续性哮喘和合并 PAR 的患者的与变应性鼻炎相关的鼻部症状。
