Dupilumab治疗不伴鼻息肉的慢性鼻窦炎患者的疗效：一项随机双盲安慰剂对照II期研究

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中文摘要

背景： 不伴鼻息肉的慢性鼻窦炎（CRSsNP）是一种异质性炎症性疾病，影响高达8%的人口。目前尚无生物制剂获批用于CRSsNP，新出现的数据提示T2高内型可能对靶向治疗优先应答。
目的： 评估dupilumab（一种靶向白细胞介素-4/白细胞介素-13信号通路的单克隆抗体）在中重度CRSsNP患者中的疗效和安全性，并探索按T2炎症内型划分的差异应答。
方法： 在一项为期6个月的随机、双盲、安慰剂对照试验中，33名中重度CRSsNP成人每2周接受dupilumab 300 mg或安慰剂。主要结局为22项鼻窦结局测试（SNOT-22）和迷你鼻结膜炎生活质量问卷（mini-RQLQ）评分的变化。次要结局包括CT鼻窦评分和急救药物的使用。在T2高患者中进行了预设亚组分析，T2高定义为明显的过敏原皮肤试验阳性或血嗜酸性粒细胞升高。
结果： Dupilumab显著改善SNOT-22（-7.0 vs 安慰剂；P<.001）和mini-RQLQ（-5.2 vs 安慰剂；P<.01）评分。T2高患者在SNOT-22上显示出数值上更大的改善（-11.3；P=.07），并在mini-RQLQ上显示出显著改善（-9.2；P<.01）。CT评分和急救药物使用的减少有利于dupilumab，但无统计学显著性。治疗耐受良好，所有参与者均完成了研究。
结论： Dupilumab与CRSsNP成人患者报告结局的 meaningful 改善相关。在T2高患者中观察到的增强获益趋势支持内型导向治疗的潜力，并强调需要更大规模的研究来评估T2靶向生物制剂在CRSsNP管理中的作用。

英文摘要

BACKGROUND: Chronic rhinosinusitis without nasal polyps (CRSsNP) is a heterogeneous inflammatory disease affecting up to 8% of the population. No biologic therapies are currently approved for CRSsNP, and emerging data suggest that T2-high endotypes may respond preferentially to targeted therapy.
OBJECTIVE: To evaluate the efficacy and safety of dupilumab, a monoclonal antibody targeting the interleukin-4/interleukin-13 signaling pathway, in patients with moderate-severe CRSsNP and to explore differential responses by T2-inflammatory endotype.
METHODS: In a 6-month, randomized, double-blind, placebo-controlled trial, 33 adults with moderate-severe CRSsNP received dupilumab 300 mg or placebo every 2 weeks. Primary outcomes were change in 22-item Sino-Nasal Outcome Test (SNOT-22) and mini-Rhinoconjunctivitis Quality of Life Questionnaire (mini-RQLQ) scores. Secondary outcomes included CT sinus scores and use of rescue medications. Prespecified subgroup analyses were performed in T2-high patients, defined by pronounced allergen skin test positivity or elevated blood eosinophils.
RESULTS: Dupilumab significantly improved SNOT-22 (-7.0 vs placebo; P<.001) and mini-RQLQ (-5.2 vs placebo; P<.01) scores. T2-high patients showed numerically greater improvement in SNOT-22 (-11.3; P=.07) and significant improvement in mini-RQLQ (-9.2; P<.01). Reductions in CT scores and rescue medication use favored dupilumab but were not statistically significant. Treatment was well tolerated, and all participants completed the study.
CONCLUSION: Dupilumab was associated with meaningful improvements in patient-reported outcomes in adults with CRSsNP. The observed trend toward enhanced benefit in T2-high patients supports the potential for endotype-directed therapy and underscores the need for larger studies to evaluate the role of T2-targeted biologics in CRSsNP management.