ISSN 1673-3770 CN 37-1437/R
山东大学耳鼻喉眼学报 ›› 2026, Vol. 40 ›› Issue (6): 83-90.
• 气道变态反应性疾病：从机制到实践 • 上一篇
赵丽,谢尔杰,唐玥玓
ZHAO Li, XIE Erjie, TANG Yuedi
摘要： 慢性鼻窦炎伴鼻息肉(chronic sinusitis with nasal polyps, CRSwNP)是一种国内外常见疾病,其疾病负担重,极大影响着患者的生活质量及身心健康。2型炎症在CRSwNP的病理生理过程中发挥关键作用,而嗜酸性粒细胞在介导2型炎症中发挥重要作用。IL-5是介导嗜酸性粒细胞增殖、激活和存活的主要细胞因子。许多靶向IL-5的生物制剂如美泊利珠单抗、瑞利珠单抗和贝那利珠单抗在CRSwNP的一系列研究中显示出一定的临床疗效。其通过抗IL-5或IL-5R降低血液及鼻息肉组织中嗜酸性粒细胞的水平从而减轻组织2型炎症成为治疗CRSwNP的新方法。尤其是美泊利珠单抗,在国外已被批准用于CRSwNP患者。本文对美泊利珠单抗、瑞利珠单抗、贝那利珠单抗三种研究较多的靶向IL-5生物制剂治疗CRSwNP的作用机制及研究现状进行综述,以期为其未来CRSwNP的治疗提供新靶点。
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| [1] Fokkens W J, Lund V J, Hopkins C, et al. European position paper on rhinosinusitis and nasal polyps 2020[J]. Rhinology, 2020, 58(Suppl S29): 1-2. DOI:10.4193/Rhin20.600 [2] 汪文华, 王广科, 武天义, 等. 根治性鼻内镜手术治疗嗜酸粒细胞增高型慢性鼻窦炎伴鼻息肉的疗效分析[J]. 临床耳鼻咽喉头颈外科杂志, 2023, 37(1): 20-24. DOI:10.13201/j.issn.2096-7993.2023.01.004 [3] 朱玉, 朱新华. TH2细胞因子在2型慢性鼻窦炎伴鼻息肉中的作用机制研究进展[J]. 山东大学耳鼻喉眼学报, 2023, 37(5): 156-161. DOI:10.6040/j.issn.1673-3770.0.2022.258 [4] 姚爽. 慢性鼻窦炎的内在型研究进展及精准医疗[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 20-29, 49. DOI:10.6040/j.issn.1673-3770.0.2021.561 [5] Wang M, Zhang N, Zheng M, et al. Cross-talk between TH2 and TH17 pathways in patients with chronic rhinosinusitis with nasal polyps[J]. J Allergy Clin Immunol, 2019, 144(5): 1254-1264. DOI:10.1016/j.jaci.2019.06.023 [6] Barretto K T, Brockman-Schneider R A, Kuipers I, et al. Human airway epithelial cells express a functional IL-5 receptor[J]. Allergy, 2020, 75(8): 2127-2130. DOI:10.1111/all.14297 [7] Han J K, Bachert C, Fokkens W, et al. Mepolizumab for chronic rhinosinusitis with nasal polyps(SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial[J]. Lancet Respir Med, 2021, 9(10): 1141-1153. DOI:10.1016/S2213-2600(21)00097-7 [8] Bachert C, Sousa A R, Lund V J, et al. Reduced need for surgery in severe nasal polyposis with mepolizumab: randomized trial[J]. J Allergy Clin Immunol, 2017, 140(4): 1024-1031.e14. DOI:10.1016/j.jaci.2017.05.044 [9] Gevaert P, van Bruaene N, Cattaert T, et al. Mepolizumab, a humanized anti-IL-5 MAb, as a treatment option for severe nasal polyposis[J]. J Allergy Clin Immunol, 2011, 128(5): 989-995.e1-8. DOI:10.1016/j.jaci.2011.07.056 [10] Gevaert P, Lang-Loidolt D, Lackner A, et al. Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps[J]. J Allergy Clin Immunol, 2006, 118(5): 1133-1141. DOI:10.1016/j.jaci.2006.05.031 [11] Bachert C, Han J K, Desrosiers M Y, et al. Efficacy and safety of benralizumab in chronic rhinosinusitis with nasal polyps: a randomized, placebo-controlled trial[J]. J Allergy Clin Immunol, 2022, 149(4): 1309-1317.e12. DOI:10.1016/j.jaci.2021.08.030 [12] Takabayashi T, Asaka D, Okamoto Y, et al. A phase II, multicenter, randomized, placebo-controlled study of benralizumab, a humanized anti-IL-5R alpha monoclonal antibody, in patients with eosinophilic chronic rhinosinusitis[J]. Am J Rhinol Allergy, 2021, 35(6): 861-870. DOI:10.1177/19458924211009429 [13] Tversky J, Lane A P, Azar A. Benralizumab effect on severe chronic rhinosinusitis with nasal polyps(CRSwNP): a randomized double-blind placebo-controlled trial[J]. Clin Exp Allergy, 2021, 51(6): 836-844. DOI:10.1111/cea.13852 [14] Desrosiers M, Diamant Z, Castelnuovo P, et al. Sustained efficacy of mepolizumab in patients with severe chronic rhinosinusitis with nasal polyps: SYNAPSE 24-week treatment-free follow-up[J]. Int Forum Allergy Rhinol, 2024, 14(1): 18-31. DOI:10.1002/alr.23219 [15] Lemiere C, Taillé C, Lee J K, et al. Impact of baseline clinical asthma characteristics on the response to mepolizumab: a post hoc meta-analysis of two phase III trials[J]. Respir Res, 2021, 22(1): 184. DOI:10.1186/s12931-021-01767-z [16] Castro M, Mathur S, Hargreave F, et al. Reslizumab for poorly controlled, eosinophilic asthma: a randomized, placebo-controlled study[J]. Am J Respir Crit Care Med, 2011, 184(10): 1125-1132. DOI:10.1164/rccm.201103-0396OC [17] Canonica G W, Harrison T W, Chanez P, et al. Benralizumab improves symptoms of patients with severe, eosinophilic asthma with a diagnosis of nasal polyposis[J]. Allergy, 2022, 77(1): 150-161. DOI:10.1111/all.14902 [18] Korn S, Bourdin A, Chupp G, et al. Integrated safety and efficacy among patients receiving benralizumab for up to 5 years[J]. J Allergy Clin Immunol Pract, 2021, 9(12): 4381-4392.e4. DOI:10.1016/j.jaip.2021.07.058 [19] Wang Q, Sun Q, Chen Q G, et al. Efficacy and safety of anti-interleukin-5 therapies in chronic rhinosinusitis with nasal polyps: a systematic review and meta-analysis of randomized controlled trials[J]. Int Arch Allergy Immunol, 2022, 183(7): 732-743. DOI:10.1159/000521859 [20] Demir M, Tunakan Dalgic C, Mete Gokmen E N, et al. The effectiveness of biological agents on chronic rhinosinusitis with nasal polyposis in patients with comorbid asthma: a multicenter real-life study from türkiye[J]. Medicina(Kaunas), 2024, 60(3): 448. DOI:10.3390/medicina60030448 [21] Gallo S, Castelnuovo P, Spirito L, et al. Mepolizumab improves outcomes of chronic rhinosinusitis with nasal polyps in severe asthmatic patients: a multicentric real-life study[J]. J Pers Med, 2022, 12(8): 1304. DOI:10.3390/jpm12081304 [22] Bajpai S, Marino M J, Rank M A, et al. Benefits of biologic therapy administered for asthma on co-existent chronic rhinosinusitis: a real-world study[J]. Int Forum Allergy Rhinol, 2021, 11(8): 1152-1161. DOI:10.1002/alr.22774 [23] Detoraki A, Tremante E, D'Amato M, et al. Mepolizumab improves Sino-nasal symptoms and asthma control in severe eosinophilic asthma patients with chronic rhinosinusitis and nasal polyps: a 12-month real-life study[J]. Ther Adv Respir Dis, 2021, 15: 17534666211009398. DOI:10.1177/17534666211009398 [24] Yilmaz I, Türk M, Nazik Baheciolu S, et al. Efficacy of mepolizumab treatment in oral corticosteroid-dependent severe eosinophilic asthma patients with chronic rhinosinusitis with nasal polyps: single center, real life study[J]. Turk J Med Sci, 2020, 50(2): 433-441. DOI:10.3906/sag-1912-62 [25] Santomasi C, Buonamico E, Dragonieri S, et al. Effects of benralizumab in a population of patients affected by severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps: a real life study[J]. Acta Biomed, 2023, 94(1): e2023028. DOI:10.23750/abm.v94i1.13474 [26] Cavaliere C, Segatto M, Ciofalo A, et al. Benralizumab reduces eosinophils and inflammatory markers in patients with severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps: a pilot real-life study[J]. Immunol Lett, 2022, 248: 70-77. DOI:10.1016/j.imlet.2022.06.009 [27] Barroso B, Valverde-Monge M, Alobid I, et al. Improvement in olfaction in patients with CRSwNP and severe asthma taking anti-IgE and anti-IL-5 biologics: a real-life study[J]. J Investig Allergol Clin Immunol, 2023, 33(1): 37-44. DOI:10.18176/jiaci.0812 [28] Frster-Ruhrmann U, Stergioudi D, Szczepek A J, et al. A real-life comparison of pulmonary and nasal outcomes in patients with severe asthma and nasal polyposis treated with T2-biologics[J]. World Allergy Organ J, 2023, 16(2): 100746. DOI:10.1016/j.waojou.2023.100746 [29] Maza-Solano J, Calvo-Henríquez C, Alobid I, et al. Nasal symptoms in asthmatic patients under treatment with anti-IL-5 monoclonal antibodies. A real-life cohort study[J]. J Clin Med, 2022, 11(23): 7056. DOI:10.3390/jcm11237056 [30] Patel G B, Kudlaty E A, Guo A, et al. Impact of type 2 targeting biologics on acute exacerbations of chronic rhinosinusitis[J]. Allergy Asthma Proc, 2021, 42(5): 417-424. DOI:10.2500/aap.2021.42.210058 [31] Meier E C, Schmid-Grendelmeier P, Steiner U C, et al. Real-life experience of monoclonal antibody treatments in chronic rhinosinusitis with nasal polyposis[J]. Int Arch Allergy Immunol, 2021, 182(8): 736-743. DOI:10.1159/000514262 [32] Bandi F, Gallo S, Preti A, et al. Effects of biological therapies on chronic rhinosinusitis in severe asthmatic patients[J]. Acta Otorhinolaryngol Ital, 2020, 40(6): 435-443. DOI:10.14639/0392-100X-N0716 [33] Granda P, Villama án E, Heinz S, et al. Compassionate use of reslizumab in a life-threatening asthma exacerbation[J]. J Investig Allergol Clin Immunol, 2024, 34(1): 60-61. DOI:10.18176/jiaci.0920 [34] Menzella F, Biava M, Bagnasco D, et al. Efficacy and steroid-sparing effect of benralizumab: has it an advantage over its competitors [J]. Drugs Context, 2019, 8: 212580. DOI:10.7573/dic.212580 [35] Lipworth B J, Chan R. The choice of biologics in patients with severe chronic rhinosinusitis with nasal polyps[J]. J Allergy Clin Immunol Pract, 2021, 9(12): 4235-4238. DOI:10.1016/j.jaip.2021.07.023 [36] Oykhman P, Paramo F A, Bousquet J, et al. Comparative efficacy and safety of monoclonal antibodies and aspirin desensitization for chronic rhinosinusitis with nasal polyposis: a systematic review and network meta-analysis[J]. J Allergy Clin Immunol, 2022, 149(4): 1286-1295. DOI:10.1016/j.jaci.2021.09.009 [37] Cai S R, Xu S L, Lou H F, et al. Comparison of different biologics for treating chronic rhinosinusitis with nasal polyps: a network analysis[J]. J Allergy Clin Immunol Pract, 2022, 10(7): 1876-1886.e7. DOI:10.1016/j.jaip.2022.02.034 [38] Agache I, Song Y, Alonso-Coello P, et al. Efficacy and safety of treatment with biologicals for severe chronic rhinosinusitis with nasal polyps: a systematic review for the EAACI guidelines[J]. Allergy, 2021, 76(8): 2337-2353. DOI:10.1111/all.14809 [39] Wu Q W, Zhang Y N, Kong W F, et al. Which is the best biologic for nasal polyps: dupilumab, omalizumab, or mepolizumab A network meta-analysis[J]. Int Arch Allergy Immunol, 2022, 183(3): 279-288. DOI:10.1159/000519228 [40] Bachert C, Han J K, Desrosiers M, et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps(liberty np sinus-24 and liberty np sinus-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials[J]. Lancet, 2019, 394(10209): 1638-1650. DOI:10.1016/S0140-6736(19)31881-1 [41] Gevaert P, Omachi T A, Corren J, et al. Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials[J]. J Allergy Clin Immunol, 2020, 146(3): 595-605. DOI:10.1016/j.jaci.2020.05.032 [42] Li W, Tang S C, Jin L. Adverse events of anti-IL-5 drugs in patients with eosinophilic asthma: a meta-analysis of randomized controlled trials and real-world evidence-based assessments[J]. BMC Pulm Med, 2024, 24(1): 70. DOI:10.1186/s12890-024-02885-2 [43] Jackson D J, Bacharier L B, Gergen P J, et al. Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA(MUPPITS-2): a randomised, double-blind, placebo-controlled, parallel-group trial[J]. Lancet, 2022, 400(10351): 502-511. DOI:10.1016/S0140-6736(22)01198-9 [44] Vittorakis S K, Giannakopoulou G, Samitas K, et al. Successful and safe treatment of severe steroid depended eosinophilic asthma with mepolizumab in a woman during pregnancy[J]. Respir Med Case Rep, 2022, 41: 101785. DOI:10.1016/j.rmcr.2022.101785 [45] 张罗. 生物制剂治疗慢性鼻窦炎鼻息肉的现状和展望[J]. 临床耳鼻咽喉头颈外科杂志, 2023, 37(11): 853-855. DOI:10.13201/j.issn.2096-7993.2023.11.001 |
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