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Efficacy and safety of GR1802 in uncontrolled chronic rhinosinusitis with nasal polyps: Placebo-controlled phase 2 trial

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机构: [1]Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing [2]Department of Pathology, Beijing TongRen Hospital, Capital Medical University, Beijing [3]Beijing Key Laboratory of Head and Neck Molecular Pathological Diagnosis, Beijing TongRen Hospital, Capital Medical University, Beijing [4]Department of Otolaryngology, The First People’s Hospital of Foshan, Foshan [5]Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an [6]Department of Otolaryngology, Head and Neck Surgery, Northern Jiangsu People’s Hospital affiliated to Yangzhou University, Yangzhou [7]Department of Otolaryngology, Eye & ENT Hospital, Fudan University, Shanghai [8]State Key Laboratory of Respiratory Disease, Department of Otolaryngology, Head and Neck Surgery, Laboratory of ENT-HNS Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou [9]Department of Otorhinolaryngology, Sichuan Provincial People’s Hospital, Chengdu [10]Department of Otorhinolaryngology, the First Affiliated Hospital of Chongqing Medical University, Chongqing [11]Department of Otorhinolaryngology, Jingzhou Hospital affiliated to Yangtze University, Jingzhou [12]Department of Otolaryngology-Head and Neck Surgery, Qilu Hospital of Shandong University, Jinan [13]Department of Otolaryngology Head and Neck Surgery, Zibo Central Hospital, Zibo [14]Department of Otorhinolaryngology, Baotou Central Hospital, Baotou [15]Department of Otorhinolaryngology, Head and Neck Surgery, the First Affiliated Hospital of Nanchang University, Nanchang [16]Department of Otorhinolaryngology–Head and Neck Surgery, Artificial Auditory Laboratory of Jiangsu Province, Institute of Audiology and Balance Science of Xuzhou Medical University, Affiliated Hospital of Xuzhou Medical University, Xuzhou [17]Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai [18]Department of Otorhinolaryngology, Tianjin Union Medical Center, Tianjin [19]Department of Otorhinolaryngology, Head and Neck Surgery, Wuhan University People’s Hospital, Wuhan [20]Department of Otorhinolaryngology, Union Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan [21]Clinical Department, Chongqing Genrix Biopharmaceutical Co Ltd, Chongqing [22]Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases of Beijing Municipal Education Commission, Beijing Key Laboratory of New Medicine and Diagnostic Technology Research of Nasal Disease, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing [23]Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing.
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关键词: Chronic rhinosinusitis nasal polyps biological therapy clinical trial

摘要:
Anti-IL-4 receptor subunit alpha (IL-4Rα) treatments can effectively treat eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). However, their impact on the overall population of patients with uncontrolled CRSwNP remains unclear.We evaluated the safety and efficacy of GR1802, a novel anti-IL-4Rα monoclonal antibody, in patients with uncontrolled CRSwNP.Seventy patients with uncontrolled CRSwNP were randomized (1:1) to receive either GR1802 (300 mg with an initial doubled dose) or placebo every 2 weeks. Primary end points were the changes from baseline in nasal polyp score and nasal congestion score at week 16. Secondary end points mainly included change from baseline in Total Nasal Symptom Score (TNSS), 22-item Sino-Nasal Outcome Test (SNOT-22) score, and Lund-Mackay score. Efficacy (exploratory) was also analyzed in ECRSwNP and non-ECRSwNP subgroups. Safety was evaluated throughout the study.In uncontrolled CRSwNP participants, GR1802 significantly improved nasal polyp score and nasal congestion score compared with placebo, with least squares mean differences of -2.1 (95% confidence interval, -2.6, -1.5) and -0.8 (95% confidence interval, -1.1, -0.4), respectively. Participants treated with GR1802 had significantly decreased TNSS, SNOT-22 score, and Lund-Mackay score. The subgroup analysis demonstrated that GR1802 improved the symptoms and quality of life in both ECRSwNP and non-ECRSwNP participants, as evidenced by changes in nasal polyp score, University of Pennsylvania Smell Identification Test score, and Lund-Mackay score. Treatment-related adverse events occurred in 19.4% of the GR1802 group and 17.6% of the placebo group.GR1802 is well tolerated and effective in treating the overall population with uncontrolled CRSwNP.Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.

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大类 | 1 区 医学
小类 | 1 区 过敏 1 区 免疫学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 过敏 1 区 免疫学
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第一作者机构: [1]Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing
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通讯机构: [1]Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing [22]Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases of Beijing Municipal Education Commission, Beijing Key Laboratory of New Medicine and Diagnostic Technology Research of Nasal Disease, Key Laboratory of Otolaryngology Head and Neck Surgery, Ministry of Education, Capital Medical University, Beijing [23]Department of Allergy, Beijing TongRen Hospital, Capital Medical University, Beijing.
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