PDF(Pubmed)
Abstract：
UNASSIGNED: Chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD) are frequent coexisting conditions and share type 2 inflammatory pathophysiology, with interleukin (IL)-4 and IL-13 as key cytokines. Dupilumab is a monoclonal antibody that blocks the shared receptor for IL-4 and IL-13. The objective of this analysis was to evaluate dupilumab\'s effect on type 2 inflammation biomarkers in patients with CRSwNP with/without coexisting asthma or NSAID-ERD from the SINUS-52 (NCT02898454) study.
UNASSIGNED: Patients received treatment with dupilumab or placebo for 52 weeks. Blood and urinary biomarkers were evaluated through 52 weeks, and nasal secretions and mucosa brushings through 24 weeks.
UNASSIGNED: Of 447 patients, 60% had coexisting asthma and 27% had coexisting NSAID-ERD. At baseline, blood eotaxin-3, eosinophils, and periostin, nasal secretion eotaxin-3, and urinary leukotriene E4 were significantly higher in patients with coexisting NSAID-ERD than without. Dupilumab reduced eotaxin-3, thymus and activation-regulated chemokine, periostin, and total immunoglobulin E in blood, eotaxin-3, periostin, IL-5, and eosinophil cationic protein in nasal secretions, and leukotriene E4 in urine. Reductions were generally similar or greater in the subgroups with asthma and NSAID-ERD than without. Dupilumab also reduced MUC5AC and mast cell counts in nasal mucosa brushings.
UNASSIGNED: Dupilumab reduced local and systemic type 2 inflammatory biomarkers in patients with CRSwNP, including mast cells in nasal mucosa and cysteinyl leukotrienes in urine. These findings provide insight into the processes driving CRSwNP and the mechanisms of dupilumab\'s therapeutic effects.
UNASSIGNED: SINUS-52 https://www.clinicaltrials.gov/ct2/show/NCT02898454.
UNASSIGNED: NCT02898454.
UNASSIGNED: Patients received treatment with dupilumab or placebo for 52 weeks. Blood and urinary biomarkers were evaluated through 52 weeks, and nasal secretions and mucosa brushings through 24 weeks.
UNASSIGNED: Of 447 patients, 60% had coexisting asthma and 27% had coexisting NSAID-ERD. At baseline, blood eotaxin-3, eosinophils, and periostin, nasal secretion eotaxin-3, and urinary leukotriene E4 were significantly higher in patients with coexisting NSAID-ERD than without. Dupilumab reduced eotaxin-3, thymus and activation-regulated chemokine, periostin, and total immunoglobulin E in blood, eotaxin-3, periostin, IL-5, and eosinophil cationic protein in nasal secretions, and leukotriene E4 in urine. Reductions were generally similar or greater in the subgroups with asthma and NSAID-ERD than without. Dupilumab also reduced MUC5AC and mast cell counts in nasal mucosa brushings.
UNASSIGNED: Dupilumab reduced local and systemic type 2 inflammatory biomarkers in patients with CRSwNP, including mast cells in nasal mucosa and cysteinyl leukotrienes in urine. These findings provide insight into the processes driving CRSwNP and the mechanisms of dupilumab\'s therapeutic effects.
UNASSIGNED: SINUS-52 https://www.clinicaltrials.gov/ct2/show/NCT02898454.
UNASSIGNED: NCT02898454.
摘要：
■慢性鼻窦炎伴鼻息肉（CRSwNP），哮喘,和非甾体类抗炎药物加重的呼吸系统疾病（NSAID-ERD）是常见的共存条件和共享2型炎症病理生理学，白细胞介素（IL）-4和IL-13作为关键细胞因子。Dupilumab是一种单克隆抗体，可阻断IL-4和IL-13的共有受体。本分析的目的是评估dupilumab对有/无合并哮喘或NSAID-ERD的CRSwNP患者的2型炎症生物标志物的影响来自SINUS-52(NCT02898454)研究。
■患者接受dupilumab或安慰剂治疗52周。通过52周评估血液和尿液生物标志物，和鼻腔分泌物和粘膜刷通过24周。
■在447名患者中，60%患有哮喘，27%患有NSAID-ERD。在基线,血eotaxin-3，嗜酸性粒细胞，和骨膜素,同时存在NSAID-ERD的患者的鼻分泌物eotaxin-3和尿白三烯E4显著高于不存在NSAID-ERD的患者.Dupilumab减少eotaxin-3，胸腺和活化调节趋化因子，骨膜素,血液中的总免疫球蛋白E，eotaxin-3骨膜素,鼻腔分泌物中的IL-5和嗜酸性粒细胞阳离子蛋白，和尿液中的白三烯E4.哮喘和NSAID-ERD亚组的降低通常相似或更大。Dupilumab还减少鼻粘膜刷洗中的MUC5AC和肥大细胞计数。
■Dupilumab降低了CRSwNP患者的局部和全身2型炎症生物标志物，包括鼻粘膜中的肥大细胞和尿液中的半胱氨酰白三烯。这些发现提供了对驱动CRSwNP的过程和dupilumab治疗效果的机制的洞察。
■SINUS-52https://www.clinicaltrials.gov/ct2/show/NCT02898454.
■NCT02898454。
■患者接受dupilumab或安慰剂治疗52周。通过52周评估血液和尿液生物标志物，和鼻腔分泌物和粘膜刷通过24周。
■在447名患者中，60%患有哮喘，27%患有NSAID-ERD。在基线,血eotaxin-3，嗜酸性粒细胞，和骨膜素,同时存在NSAID-ERD的患者的鼻分泌物eotaxin-3和尿白三烯E4显著高于不存在NSAID-ERD的患者.Dupilumab减少eotaxin-3，胸腺和活化调节趋化因子，骨膜素,血液中的总免疫球蛋白E，eotaxin-3骨膜素,鼻腔分泌物中的IL-5和嗜酸性粒细胞阳离子蛋白，和尿液中的白三烯E4.哮喘和NSAID-ERD亚组的降低通常相似或更大。Dupilumab还减少鼻粘膜刷洗中的MUC5AC和肥大细胞计数。
■Dupilumab降低了CRSwNP患者的局部和全身2型炎症生物标志物，包括鼻粘膜中的肥大细胞和尿液中的半胱氨酰白三烯。这些发现提供了对驱动CRSwNP的过程和dupilumab治疗效果的机制的洞察。
■SINUS-52https://www.clinicaltrials.gov/ct2/show/NCT02898454.
■NCT02898454。
