杭州浙大迪迅生物基因工程有限公司Allergy：Dupilumab可减轻伴鼻息肉慢性鼻窦炎中局部的2型促炎生物标志物
发布日期：2021-04-09
原标题：伴鼻息肉慢性鼻窦炎中Dupilumab可减轻局部2型促炎生物标志物
方法：CRSwNP患者采用每周300 mg Dupilumab或安慰剂治疗16周后，通过免疫测定技术测量其鼻分泌物和鼻息肉组织匀浆中的细胞因子、趋化因子和总免疫球蛋白E（IgE）的水平。
结果：与eotaxin-3安慰剂（-30.06 vs -0.86 pg / mL; P = 0.0008）和总IgE（-7.90对-1.86 IU / mL；P = 0.022）相比，Dupilumab治疗后鼻分泌物中2型生物标志物的浓度（0~16周最小二乘均值的曲线下面积相对于基线的变化）有所降低。与基线相比，Dupilumab治疗还降低了第16周鼻息肉组织中2型生物标志物的水平，如嗜酸性阳离子蛋白（P = 0.008），eotaxin-2（P = 0.008），eotaxin-3（P = 0.031），肺和活化调节趋化因子（P = 0.016），IgE（P = 0.023）和IL-13（P = 0.031）。
结论：Dupilumab治疗减少了CRSwNP患者鼻分泌物和鼻息肉组织中2型炎症的多种生物标志物，表明IL-4Rα信号的拮抗作用抑制了IL-4或IL-13依赖性过程，例如粘膜IgE的形成以及趋化因子的表达将炎症细胞吸引到鼻粘膜。
延伸阅读
Allergy
DOI: 10.1111/all.13685
Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a type 2-mediated inflammatory disease associated with significant clinical, social, and economic burdens and high unmet therapeutic need. Dupilumab, a fully human monoclonal antibody targeting the interleukin-4 receptor α (IL-4Rα) subunit, demonstrated efficacy and acceptable safety in CRSwNP and other type 2 diseases (eg, atopic dermatitis and asthma). We now report the local effects of dupilumab on type 2 inflammatory biomarkers in nasal secretions and nasal polyp tissues of patients with CRSwNP in a randomized, placebo-controlled, phase 2 trial
Methods: Cytokines, chemokines, and total immunoglobulin E (IgE) levels were measured using immunoassay techniques in nasal secretions and nasal polyp tissue homogenates of CRSwNP patients receiving dupilumab 300 mg or placebo weekly for 16 weeks.
Results: With dupilumab, type 2 biomarker concentrations decreased in nasal secretions (least squares mean area under the curve from 0 to 16 weeks for the change from baseline) vs placebo for eotaxin-3 (-30.06 vs -0.86 pg/mL; P = 0.0008) and total IgE (-7.90 vs -1.86 IU/mL; P = 0.022). Dupilumab treatment also decreased type 2 biomarker levels in nasal polyp tissues at Week 16 vs baseline for eosinophilic cationic protein (P = 0.008), eotaxin-2 (P = 0.008), eotaxin-3 (P = 0.031), pulmonary and activation-regulated chemokine (P = 0.016), IgE (P = 0.023), and IL-13 (P = 0.031).
Conclusion: Dupilumab treatment reduced multiple biomarkers of type 2 inflammation in nasal secretions and polyp tissues of patients with CRSwNP, demonstrating that antagonism of IL-4Rα signaling suppresses IL-4-/IL-13-dependent processes, such as mucosal IgE formation, as well as the expression of chemokines attracting inflammatory cells to the nasal mucosa.
Author:
Karin Jonstam
Correspondence:
Brian N Swanson, Leda P Mannent, Lars-Olaf Cardell, Nian Tian, Ying Wang, Donghui Zhang, Chunpeng Fan, Gabriele Holtappels, Jennifer D Hamilton, Annette Grabher, Neil M H Graham, Gianluca Pirozzi, Claus Bachert.
All Author:
Karin Jonstam, Brian N Swanson, Leda P Mannent, Lars-Olaf Cardell, Nian Tian, Ying Wang, Donghui Zhang, Chunpeng Fan, Gabriele Holtappels, Jennifer D Hamilton, Annette Grabher, Neil M H Graham, Gianluca Pirozzi, Claus Bachert.
2019-1-21 Article
创建过敏性疾病的科研、科普知识交流平台，为过敏患者提供专业诊断、治疗、预防的共享平台。
——浙大迪迅 译
背景：伴鼻息肉慢性鼻窦炎（CRSwNP）是2型介导的炎症性疾病，该类疾病与重要的临床、社会和经济负担以及难以满足的治疗需求相关。靶向结合人白介素4受体α（IL-4Rα）亚基的全人单克隆抗体Dupilumab在CRSwNP和其他2型疾病（如特应性皮炎和哮喘）中显示出治疗效果和可接受的安全性。现在，我们通过一项随机且有安慰剂作为对照的2期临床试验，报告了Dupilumab对CRSwNP患者鼻分泌物和鼻息肉组织中2型炎症生物标记物的局部作用。方法：CRSwNP患者采用每周300 mg Dupilumab或安慰剂治疗16周后，通过免疫测定技术测量其鼻分泌物和鼻息肉组织匀浆中的细胞因子、趋化因子和总免疫球蛋白E（IgE）的水平。
结果：与eotaxin-3安慰剂（-30.06 vs -0.86 pg / mL; P = 0.0008）和总IgE（-7.90对-1.86 IU / mL；P = 0.022）相比，Dupilumab治疗后鼻分泌物中2型生物标志物的浓度（0~16周最小二乘均值的曲线下面积相对于基线的变化）有所降低。与基线相比，Dupilumab治疗还降低了第16周鼻息肉组织中2型生物标志物的水平，如嗜酸性阳离子蛋白（P = 0.008），eotaxin-2（P = 0.008），eotaxin-3（P = 0.031），肺和活化调节趋化因子（P = 0.016），IgE（P = 0.023）和IL-13（P = 0.031）。
结论：Dupilumab治疗减少了CRSwNP患者鼻分泌物和鼻息肉组织中2型炎症的多种生物标志物，表明IL-4Rα信号的拮抗作用抑制了IL-4或IL-13依赖性过程，例如粘膜IgE的形成以及趋化因子的表达将炎症细胞吸引到鼻粘膜。
延伸阅读
Allergy
[IF:8.706]
Dupilumab reduces local type 2 pro-inflammatory biomarkers in chronic rhinosinusitis with nasal polyposisDOI: 10.1111/all.13685
Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a type 2-mediated inflammatory disease associated with significant clinical, social, and economic burdens and high unmet therapeutic need. Dupilumab, a fully human monoclonal antibody targeting the interleukin-4 receptor α (IL-4Rα) subunit, demonstrated efficacy and acceptable safety in CRSwNP and other type 2 diseases (eg, atopic dermatitis and asthma). We now report the local effects of dupilumab on type 2 inflammatory biomarkers in nasal secretions and nasal polyp tissues of patients with CRSwNP in a randomized, placebo-controlled, phase 2 trial
Methods: Cytokines, chemokines, and total immunoglobulin E (IgE) levels were measured using immunoassay techniques in nasal secretions and nasal polyp tissue homogenates of CRSwNP patients receiving dupilumab 300 mg or placebo weekly for 16 weeks.
Results: With dupilumab, type 2 biomarker concentrations decreased in nasal secretions (least squares mean area under the curve from 0 to 16 weeks for the change from baseline) vs placebo for eotaxin-3 (-30.06 vs -0.86 pg/mL; P = 0.0008) and total IgE (-7.90 vs -1.86 IU/mL; P = 0.022). Dupilumab treatment also decreased type 2 biomarker levels in nasal polyp tissues at Week 16 vs baseline for eosinophilic cationic protein (P = 0.008), eotaxin-2 (P = 0.008), eotaxin-3 (P = 0.031), pulmonary and activation-regulated chemokine (P = 0.016), IgE (P = 0.023), and IL-13 (P = 0.031).
Conclusion: Dupilumab treatment reduced multiple biomarkers of type 2 inflammation in nasal secretions and polyp tissues of patients with CRSwNP, demonstrating that antagonism of IL-4Rα signaling suppresses IL-4-/IL-13-dependent processes, such as mucosal IgE formation, as well as the expression of chemokines attracting inflammatory cells to the nasal mucosa.
Author:
Karin Jonstam
Correspondence:
Brian N Swanson, Leda P Mannent, Lars-Olaf Cardell, Nian Tian, Ying Wang, Donghui Zhang, Chunpeng Fan, Gabriele Holtappels, Jennifer D Hamilton, Annette Grabher, Neil M H Graham, Gianluca Pirozzi, Claus Bachert.
All Author:
Karin Jonstam, Brian N Swanson, Leda P Mannent, Lars-Olaf Cardell, Nian Tian, Ying Wang, Donghui Zhang, Chunpeng Fan, Gabriele Holtappels, Jennifer D Hamilton, Annette Grabher, Neil M H Graham, Gianluca Pirozzi, Claus Bachert.
2019-1-21 Article
创建过敏性疾病的科研、科普知识交流平台，为过敏患者提供专业诊断、治疗、预防的共享平台。
