Advances in Biologics for Rhinology: Evidence and Prospects in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) and Allergic Rhinitis

Yuehao Lu ,  Duanshali Liu ,  Yilun Zou ,  Junlong Ma ,  Bilan Xiong ,  Shujun Sun ORCID

    Received: 12 January 2026; Revised: 25 February 2026; Accepted: 6 March 2026; Published: 19 March 2026

    Abstract

    Chronic rhinosinusitis with nasal polyps (CRSwNP) and allergic rhinitis (AR) are common upper-airway inflammatory disorders that often coexist, significantly decrease quality of life, and recur even when treated with intranasal or systemic therapy or surgery. Growing mechanistic insights, such as the role of type 2 inflammation driven by epithelial “alarmins” (TSLP, IL-25, IL-33) and downstream cytokines (IL-4/IL-13, IL-5), together with IgE-mediated effector pathways, have led to the accelerated clinical use of targeted biologics. Here, we summarize the shared immunopathogenesis of CRSwNP and AR, highlight treatable endotypes and practical biomarkers (e.g., blood eosinophils, total IgE, FeNO, and disease-specific symptom and quality-of-life scores), and map these features to therapeutic targets. We summarize evidence for approved agents, including anti-IgE omalizumab; anti-IL-5/IL-5R therapies mepolizumab, reslizumab, and benralizumab; and anti-IL-4R therapy dupilumab, focusing on clinically significant outcomes such as nasal polyp burden, nasal obstruction, olfaction, SNOT-22/TNSS improvement, reduction in systemic corticosteroid use, surgery rates, safety, and limitations. Given that many patients have multimorbidity with asthma or atopic dermatitis, we also outline how unified airway management can guide multidisciplinary decision-making and the use of shared endpoints. Practical considerations such as initiation criteria, response assessment, treatment switching, and economic or access barriers are summarized to inform real-world implementation and future research.

    Keywords

    References

    1. 1. Grimm, D.; Hwang, P.H.; Lin, Y.T. The link between allergic rhinitis and chronic rhinosinusitis. Curr. Opin. Otolaryngol. Head Neck Surg. 2023, 31, 3–10. DOI: https://doi.org/10.1097/MOO.0000000000000865
    2. 2. Cheon, J.; Kim, B.; Lee, J.; et al. Functions and clinical applications of extracellular vesicles in Th2 cellmediated airway inflammatory diseases: A review. Int. J. Mol. Sci. 2024, 25, 9455. DOI: https://doi.org/10.3390/ijms25179455
    3. 3. Kariyawasam, H.H.; James, L.K. B cells and upper airway disease: allergic rhinitis and chronic rhinosinusitis with nasal polyps evaluated. Expert Rev. Clin. Immunol. 2021, 17, 445–459. DOI: https://doi.org/10.1080/1744666X.2021.1905527
    4. 4. Peters, A.T.; Tan, B.K.; Stevens, W.W.; et al. Consultation for chronic rhinosinusitis with nasal polyps and asthma: Clinical presentation, diagnostic workup, and treatment options. J. Allergy Clin. Immunol.: Pract. 2024, 12, 2898–2905. DOI: https://doi.org/10.1016/j.jaip.2024.07.019
    5. 5. Castillo, J.A.; Plaza, V.; Rodrigo, G.; et al. Chronic rhinosinusitis with nasal polyps and allergic rhinitis as different multimorbid treatable traits in asthma. J. Allergy Clin. Immunol. Glob. 2023, 2, 100134. DOI: https://doi.org/10.1016/j.jacig.2023.100134
    6. 6. Jung, C.G.; Buchheit, K.M.; Bochenek, G.; et al. Upper airway comorbidities of asthma. J. Allergy Clin. Immunol. 2024, 154, 1343–1354. DOI: https://doi.org/10.1016/j.jaci.2024.10.007
    7. 7. Bachert, C.; Brusselle, G.; Castillo Vizuete, J.A.; et al. Consensus from European experts on severe eosinophilic asthma and chronic rhinosinusitis with nasal polyps: Results from the OverSEA Delphi study. J. Allergy Clin. Immunol. Glob. 2025, 4, 100529. DOI: https://doi.org/10.1016/j.jacig.2025.100529
    8. 8. Ciprandi, G. Budesonide aqueous nasal spray: An updated review in managing chronic rhinosinusitis with nasal polyps. Panminerva Med. 2024, 66, 317–323.
    9. 9. Licari, A.; Castagnoli, R.; Marseglia, A.; et al. Dupilumab to treat type 2 inflammatory diseases in children and adolescents. Paediatr. Drugs 2020, 22, 295–310.
    10. 10. Geng, B.; Dilley, M.; Anterasian, C. Biologic therapies for allergic rhinitis and nasal polyposis. Curr. Allergy Asthma Rep. 2021, 21, 36. DOI: https://doi.org/10.1007/s11882-021-01013-y
    11. 11. Alska, E.; Łaszczych, D.; NapiórkowskaBaran, K.; et al. Advances in biologic therapies for allergic diseases: Current trends, emerging agents, and future perspectives. J. Clin. Med. 2025, 14, 1079. DOI: https://doi.org/10.3390/jcm14041079
    12. 12. Nettis, E.; Brussino, L.; Patella, V.; et al. Effectiveness and safety of dupilumab in patients with chronic rhinosinusitis with nasal polyps and associated comorbidities: A multicentric prospective study in real life. Clin. Mol. Allergy 2022, 20, 6.
    13. 13. Long, S.; Wang, H.; Li, W.; et al. Advancements and future directions in chronic rhinosinusitis: Understanding inflammatory mechanisms (2000–2023). Eur. Arch. Otorhinolaryngol. 2025, 282, 2899–2909.
    14. 14. Boiko, N.V.; Lodochkina, O.E.; Kit, M.M.; et al. Impact of reslizumab on the course of chronic rhinosinusitis in patients with eosinophilic asthma. Vestn. Otorinolaringol. 2021, 86, 43–48. DOI: https://doi.org/10.17116/otorino20218602143
    15. 15. Gevaert, P.; Mullol, J.; Saenz, R.; et al. Omalizumab improves sinonasal outcomes in patients with chronic rhinosinusitis with nasal polyps regardless of allergic status. Ann. Allergy Asthma Immunol. 2024, 132, 355–362.
    16. 16. Zhou, Y.; Liu, Z.; Liu, Y. The potential roles and mechanisms of chitinase3like1 in the pathogenesis of type 2biased airway diseases. Clin. Immunol. 2023, 257, 109856. DOI: https://doi.org/10.1016/j.clim.2023.109856
    17. 17. Cergan, R.; Berghi, O.; Dumitru, M.; et al. Interleukin 8 molecular interplay in allergic rhinitis and chronic rhinosinusitis with nasal polyps: A scoping review. Life (Basel) 2025, 15, 469. DOI: https://doi.org/10.3390/life15030469
    18. 18. Saheb SharifAskari, F.; Hafezi, S.; Hachim, I.; et al. AntiIL4Rα aptamer reduces IL4 signalling and formation of nasal polyps. ERJ Open Res. 2025, 11, 3.
    19. 19. Klimek, L.; Becker, S.; Haxel, B.; et al. Different immunological types of CRSwNP in the context of the new European EAACI nomenclature. HNO 2025, 74, 174–182.
    20. 20. Gevaert, P.; Han, J.K.; Smith, S.G.; et al. The roles of eosinophils and interleukin5 in the pathophysiology of chronic rhinosinusitis with nasal polyps. Int. Forum Allergy Rhinol. 2020, 12, 1413–1423. DOI: https://doi.org/10.1002/alr.22994
    21. 21. Bai, J.; Tan, B.K. B lineage cells and IgE in allergic rhinitis and chronic rhinosinusitis with nasal polyps and the role of omalizumab treatment. Am. J. Rhinol. Allergy 2023, 37, 182–192. DOI: https://doi.org/10.1177/19458924221147770
    22. 22. Peters, A.T.; Han, J.K.; Heffler, E.; et al. Thymic stromal lymphopoietin as a therapeutic target in patients with chronic rhinosinusitis and nasal polyps. Clin. Exp. Immunol. 2025, 219, uxaf041. DOI: https://doi.org/10.1093/cei/uxaf041
    23. 23. Liu, Y.; Fu, L.; Liu, Z. The role and clinical relevance of osteopontin in allergic airway diseases. J. Clin. Med. 2023, 12, 2433. DOI: https://doi.org/10.3390/jcm12062433
    24. 24. Ghezzi, M.; Pozzi, E.; Abbattista, L.; et al. Barrier impairment and type 2 inflammation in allergic diseases: The pediatric perspective. Children (Basel) 2021, 8, 1165. DOI: https://doi.org/10.3390/children8121165
    25. 25. Nocera, A.L.; Mueller, S.K.; Workman, A.D.; et al. Cystatin SN is a potent upstream initiator of epithelialderived type 2 inflammation in chronic rhinosinusitis. J. Allergy Clin. Immunol. 2022, 150, 872–881. DOI: https://doi.org/10.1016/j.jaci.2022.04.034
    26. 26. Chang, L.; Wang, Z.; Li, S.; et al. Type 2 inflammation suppression by T-regulatory cells attenuates the eosinophil recruitment in mucosa of chronic sinusitis. Clin. Sci. 2020, 134, 123–138. DOI: https://doi.org/10.1042/CS20190388
    27. 27. Lei, C.; Jiang, J.; Zhang, Y.; et al. Role and function of regulatory T cells in chronic rhinosinusitis with nasal polyposis. J. Immunol. Res. 2022, 2022, 1144563. DOI: https://doi.org/10.1155/2022/1144563
    28. 28. Chegini, Z.; Didehdar, M.; Khoshbayan, A.; et al. The role of Staphylococcus aureus enterotoxin B in chronic rhinosinusitis with nasal polyposis. Cell Commun. Signal. 2022, 20, 29.
    29. 29. JuraSzoltys, E.; NiemiecGórska, A.; Glück, J.; et al. EEvaluation of Rhinological Symptoms and Quality of Life in Patients with Allergic or Eosinophilic Severe Uncontrolled Asthma Treated with Anti-IgE or Anti-IL5 Therapy: A Real-Live Study. Int. Arch. Allergy Immunol. 2025, 186, 1033–1043. DOI: https://doi.org/10.1159/000544039
    30. 30. Roland, L.T.; Levy, J.M. Knowledge gaps and research needs for biologic therapy in rhinology practice. Otolaryngol. Clin. North Am. 2021, 54, 709–716. DOI: https://doi.org/10.1016/j.otc.2021.04.002
    31. 31. Liu, X.; Charn, T.C.; Wang, D.Y. Mepolizumab in chronic rhinosinusitis with nasal polyposis. Immunotherapy 2023, 15, 1105–1116. DOI: https://doi.org/10.2217/imt-2023-0026
    32. 32. FörsterRuhrmann, U.; Stergioudi, D.; Szczepek, A.J.; et al. A reallife comparison of pulmonary and nasal outcomes in patients with severe asthma and nasal polyposis treated with T2biologics. World Allergy Organ. J. 2023, 16, 100746. DOI: https://doi.org/10.1016/j.waojou.2023.100746
    33. 33. Carney, A.S.; Smith, P.K. Current understanding of the role of eosinophils in chronic rhinosinusitis with nasal polyps and implications for treatment with mepolizumab and benralizumab. Am. J. Rhinol. Allergy 2023, 37, 175–181. DOI: https://doi.org/10.1177/19458924221149270
    34. 34. Chen, J.; Zhang, C.; Zhang, Q.; et al. Targeting IL4/IL13 signaling pathways in chronic rhinosinusitis with nasal polyps: from mechanisms to therapies. Clin. Rev. Allergy Immunol. 2025, 68, 87. DOI: https://doi.org/10.1007/s12016-025-09097-4
    35. 35. Ogulur, I.; Mitamura, Y.; Yazici, D.; et al. Type 2 immunity in allergic diseases. Cell. Mol. Immunol. 2025, 22, 211–242. DOI: https://doi.org/10.1038/s41423-025-01261-2
    36. 36. Park, J.; Jang, J.Y.; Kim, J.H.; et al. SLC27A2 marks lipid peroxidation in nasal epithelial cells driven by type 2 inflammation in chronic rhinosinusitis with nasal polyps. Exp. Mol. Med. 2025, 57, 856–871. DOI: https://doi.org/10.1038/s12276-025-01440-1
    37. 37. Han, X.; Krempski, J.W.; Nadeau, K. Advances and novel developments in mechanisms of allergic inflammation. Allergy 2020, 75, 3100–3111. DOI: https://doi.org/10.1111/all.14632
    38. 38. Gao, Y.D.; Wang, Z.J.; Ogulur, I.; et al. The evolution, immunopathogenesis and biomarkers of type 2 inflammation in common allergic disorders. Allergy 2025, 80, 1848–1877. DOI: https://doi.org/10.1111/all.16620
    39. 39. Gevaert, P.; Omachi, T.A.; Corren, J.; et al. Efficacy and safety of omalizumab in nasal polyposis: Two randomized phase 3 trials. J. Allergy Clin. Immunol. 2020, 146, 595–605. DOI: https://doi.org/10.1016/j.jaci.2020.05.032
    40. 40. Gevaert, P.; Saenz, R.; Corren, J.; et al. Long-term efficacy and safety of omalizumab for nasal polyposis in an open-label extension study. J. Allergy Clin. Immunol. 2022, 149, 957–965. DOI: https://doi.org/10.1016/j.jaci.2021.07.045
    41. 41. 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. Medicina (Kaunas) 2024, 60, 448. DOI: https://doi.org/10.3390/medicina60030448
    42. 42. Kariyawasam, H.H.; James, L.K. Chronic rhinosinusitis with nasal polyps: Targeting IgE with anti-IgE omalizumab therapy. Drug Des. Dev. Ther. 2020, 14, 5483–5494. DOI: https://doi.org/10.2147/DDDT.S226575
    43. 43. Yu, J.; Yan, B.; Shen, S.; et al. IgE directly affects eosinophil migration in chronic rhinosinusitis with nasal polyps through CCR3 and predicts the efficacy of omalizumab. J. Allergy Clin. Immunol. 2024, 153, 447–460. DOI: https://doi.org/10.1016/j.jaci.2023.09.041
    44. 44. Meltzer, E.O.; Mullol, J.; Ko, J.; et al. Omalizumab improves sleep and health status for patients with chronic rhinosinusitis with nasal polyps: An analysis of randomized clinical trials. Int. Forum Allergy Rhinol. 2024, 14, 1163–1172. DOI: https://doi.org/10.1002/alr.23322
    45. 45. Vogt, F.; Sahota, J.; Bidder, T.; et al. Chronic rhinosinusitis with and without nasal polyps and asthma: Omalizumab improves residual anxiety but not depression. Clin. Transl. Allergy 2021, 11, e12002. DOI: https://doi.org/10.1002/clt2.12002
    46. 46. Yong, M.; Kirubalingam, K.; Desrosiers, M.Y.; et al. Cost-effectiveness analysis of biologics for the treatment of chronic rhinosinusitis with nasal polyps in Canada. Allergy Asthma Clin. Immunol. 2023, 19, 90. DOI: https://doi.org/10.1186/s13223-023-00823-1
    47. 47. De Prado Gomez, L.; Khan, A.H.; Peters, A.T.; et al. Efficacy and safety of dupilumab versus omalizumab in chronic rhinosinusitis with nasal polyps and asthma: EVEREST trial design. Am. J. Rhinol. Allergy 2022, 36, 788–795. DOI: https://doi.org/10.1177/19458924221112211
    48. 48. Jackson, D.J.; Wechsler, M.E.; Brusselle, G.; et al. Targeting the IL-5 pathway in eosinophilic asthma: A comparison of anti-IL-5 versus anti-IL-5 receptor agents. Allergy 2024, 79, 2943–2952. DOI: https://doi.org/10.1111/all.16346
    49. 49. Olivieri, B.; Tinazzi, E.; Caminati, M.; et al. Biologics for the treatment of allergic conditions: Eosinophil disorders. Immunol. Allergy Clin. North Am. 2020, 40, 649–665. DOI: https://doi.org/10.1016/j.iac.2020.07.001
    50. 50. Wang, Q.; Sun, Q.; Chen, Q.; 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. Int. Arch. Allergy Immunol. 2022, 183, 732–743. DOI: https://doi.org/10.1159/000521859
    51. 51. Guo, C.L.; Wang, C.S.; Liu, Z. Clinical and biological markers in disease and biologics to treat chronic rhinosinusitis. Curr. Opin. Allergy Clin. Immunol. 2022, 22, 16–23. DOI: https://doi.org/10.1097/ACI.0000000000000799
    52. 52. 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. Clin. Med. 2022, 11, 7056. DOI: https://doi.org/10.3390/jcm11237056
    53. 53. Lombardi, C.; Comberiati, P.; Ridolo, E.; et al. Anti-IL-5 pathway agents in eosinophilic-associated disorders across the lifespan. Drugs 2024, 84, 661–684. DOI: https://doi.org/10.1007/s40265-024-02037-0
    54. 54. Yang, C.; Guo, L.; Wang, Y.; et al. The advance on pathophysiological mechanisms of type 2 chronic rhinosinusitis with nasal polyposis. Front. Allergy 2025, 6, 1599797. DOI: https://doi.org/10.3389/falgy.2025.1599797
    55. 55. Kagoshima, H.; Hori, R.; Kojima, T.; et al. Successful treatment of eosinophilic chronic rhinosinusitis and eosinophilic otitis media using the anti-IL-5 receptor monoclonal antibody benralizumab: A case report. Respir. Med. Case Rep. 2020, 30, 101135. DOI: https://doi.org/10.1016/j.rmcr.2020.101135
    56. 56. Pelaia, C.; Busceti, M.T.; Crimi, C.; et al. Real-life effects of benralizumab on exacerbation number and lung hyperinflation in atopic patients with severe eosinophilic asthma. Biomed. Pharmacother. 2020, 129, 110444. DOI: https://doi.org/10.1016/j.biopha.2020.110444
    57. 57. Giossi, R.; Pani, A.; Schroeder, J.; et al. Exploring the risk of infection events in patients with asthma receiving anti-IL-5 monoclonal antibodies: A rapid systematic review and meta-analysis. Heliyon 2024, 10, e23725. DOI: https://doi.org/10.1016/j.heliyon.2023.e23725
    58. 58. Zou, S.P.; Yang, H.Y.; Ouyang, M.; et al. Post-marketing safety of anti-IL-5 monoclonal antibodies: An analysis of the FDA adverse event reporting system (FAERS). Expert Opin. Drug Saf. 2024, 23, 353–362. DOI: https://doi.org/10.1080/14740338.2023.2251382
    59. 59. Jackson, D.J.; Korn, S.; Mathur, S.K.; et al. Safety of eosinophil-depleting therapy for severe, eosinophilic asthma: Focus on benralizumab. Drug Saf. 2020, 43, 409–425. DOI: https://doi.org/10.1007/s40264-020-00926-3
    60. 60. Kariyawasam, H.H. Chronic rhinosinusitis with nasal polyps: mechanistic insights from targeting IL-4 and IL-13 via IL-4Rα inhibition with dupilumab. Expert Rev. Clin. Immunol. 2020, 16, 1115–1125. DOI: https://doi.org/10.1080/1744666X.2021.1847083
    61. 61. Pelaia, C.; Heffler, E.; Crimi, C.; et al. Interleukins 4 and 13 in asthma: Key pathophysiologic cytokines and druggable molecular targets. Front. Pharmacol. 2022, 13, 851940. DOI: https://doi.org/10.3389/fphar.2022.851940
    62. 62. Kariyawasam, H.H.; James, L.K.; Gane, S.B. Dupilumab: Clinical efficacy of blocking IL-4/IL-13 signalling in chronic rhinosinusitis with nasal polyps. Drug Des. Dev. Ther. 2020, 14, 1757–1769. DOI: https://doi.org/10.2147/DDDT.S243053
    63. 63. Hoy, S.M. Dupilumab: A review in chronic rhinosinusitis with nasal polyps. Drugs 2020, 80, 711–717. DOI: https://doi.org/10.1007/s40265-020-01298-9
    64. 64. Gal, A.; Gravier-Dumonceau, R.; Penicaud, M.; et al. Efficacy of dupilumab in real-life settings: A STROBE study. Eur. Arch. Otorhinolaryngol. 2024, 281, 4781–4788. DOI: https://doi.org/10.1007/s00405-024-08553-9
    65. 65. Lombardo, N.; D’Ecclesia, A.; Chiarella, E.; et al. Real-world evaluation of dupilumab in the long-term management of eosinophilic chronic rhinosinusitis with nasal polyps: A focus on IL-4 and IL-13 receptor blockade. Medicina (Kaunas) 2024, 60, 1996. DOI: https://doi.org/10.3390/medicina60121996
    66. 66. Yeh, C.F.; Lan, M.Y.; Lin, C.C.; et al. Dual blockade of IL-4 and IL-13 with dupilumab ameliorates sensorineural olfactory dysfunction in mice with eosinophilic sinonasal inflammation. Rhinology 2025, 63, 32–42.
    67. 67. Fieux, M.; Carsuzaa, F.; Bellanger, Y.; et al. Dupilumab prevents nasal epithelial function alteration by IL-4 in vitro: Evidence for its efficacy. Int. Forum Allergy Rhinol. 2024, 14, 1337–1349. DOI: https://doi.org/10.1002/alr.23343
    68. 68. Bachert, C.; Laidlaw, T.M.; Cho, S.H.; et al. Effect of dupilumab on type 2 biomarkers in chronic rhinosinusitis with nasal polyps: SINUS-52 study results. Ann. Otol. Rhinol. Laryngol. 2023, 132, 1649–1661. DOI: https://doi.org/10.1177/00034894231176334
    69. 69. Peters, A.T.; Wagenmann, M.; Bernstein, J.A.; et al. Dupilumab efficacy in patients with chronic rhinosinusitis with nasal polyps with and without allergic rhinitis. Allergy Asthma Proc. 2023, 44, 265–274. DOI: https://doi.org/10.2500/aap.2023.44.230015
    70. 70. Cheng, F.; Wang, Y.; Gao, Y.; et al. Current understanding of epithelial-derived alarmins in chronic rhinosinusitis with nasal polyps. Clin. Rev. Allergy Immunol. 2025, 68, 59. DOI: https://doi.org/10.1007/s12016-025-09073-y
    71. 71. Priessnitz, J.; Jung, J.; Han, J.K.; et al. Evaluating the efficacy and safety of tezepelumab in the treatment of chronic rhinosinusitis with nasal polyps. Immunotherapy 2025, 17, 903–912. DOI: https://doi.org/10.1080/1750743X.2025.2567844
    72. 72. Danto, S.I.; Tsamandouras, N.; Reddy, P.; et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of PF-06817024 in healthy participants and patients with chronic rhinosinusitis with nasal polyps or atopic dermatitis: A phase 1 randomized double-blind placebo-controlled study. J. Clin. Pharmacol. 2024, 64, 529–543. DOI: https://doi.org/10.1002/jcph.2360
    73. 73. Liao, G.; Nakayama, T.; Zhu, B.; et al. Multi-scaled transcriptomics of chronically inflamed nasal epithelium reveals immune-epithelial dynamics and tissue remodeling in nasal polyp formation. Immunity 2025, 58, 2593–2608. DOI: https://doi.org/10.1016/j.immuni.2025.08.009
    74. 74. Tsabouri, S.; Ntritsos, G.; Koskeridis, F.; et al. Omalizumab for the treatment of allergic rhinitis: A systematic review and meta-analysis. Rhinology 2021, 59, 501–510. DOI: https://doi.org/10.4193/Rhin21.159
    75. 75. Cavaliere, C.; Begvarfaj, E.; Incorvaia, C.; et al. Long-term omalizumab efficacy in allergic rhinitis. Immunol. Lett. 2020, 227, 81–87. DOI: https://doi.org/10.1016/j.imlet.2020.08.002
    76. 76. Goto, T.; Miwa, T.; Hashimoto, K.; et al. Evaluating the efficacy of omalizumab in severe cedar seasonal allergic rhinitis in Japan. Cureus 2024, 16, e63714. DOI: https://doi.org/10.7759/cureus.63714
    77. 77. Başer, E.; Degirmenci, P.B.; Arslan, I.B.; et al. Effect of omalizumab on nasal symptoms in asthma and perennial allergic rhinitis. J. Coll. Physicians Surg. Pak. 2020, 30, 1170–1174. DOI: https://doi.org/10.29271/jcpsp.2020.11.1170
    78. 78. Bayar Muluk, N.; Cingi, C. Biologics in allergic rhinitis. Eur. Rev. Med. Pharmacol. Sci. 2023, 27, 43–52. DOI: https://doi.org/10.26355/eurrev_202310_34069
    79. 79. De Filippo, M.; Votto, M.; Caminiti, L.; et al. Omalizumab and allergen immunotherapy for respiratory allergies: A mini-review from the Allergen-Immunotherapy Committee of the Italian Society of Pediatric Allergy and Immunology (SIAIP). Allergol. Immunopathol. 2022, 50, 47–52. DOI: https://doi.org/10.15586/aei.v50i6.495
    80. 80. Zhang, Y.; Xi, L.; Gao, Y.; et al. Omalizumab is effective in the preseasonal treatment of seasonal allergic rhinitis. Clin. Transl. Allergy 2022, 12, e12094. DOI: https://doi.org/10.1002/clt2.12094
    81. 81. Li, M.; Li, P.; Sun, Y.; et al. Diagnostic value of image enhancement endoscopy in sinonasal malignancy. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2025, 60, 420–426. DOI: https://doi.org/10.3760/cma.j.cn115330-20240612-00346 (in Chinese)
    82. 82. Zhao, Z.; Deng, Y.; Xiang, L.; et al. The ratio of total IgE level at week 16 to baseline significantly correlated with the clinical response to omalizumab in moderate-to-severe allergic rhinitis patients. Int. Immunopharmacol. 2023, 122, 110623. DOI: https://doi.org/10.1016/j.intimp.2023.110623
    83. 83. Hirano, K.; Suzaki, I.; Okuzawa, N.; et al. Omalizumab reduces allergic rhinitis symptoms due to Japanese cedar pollen by improving eosinophilic inflammation. Rhinology 2025, 63, 116–117. DOI: https://doi.org/10.4193/Rhin24.105
    84. 84. Lv, R.; Shan, J.; Sun, A.; et al. Research progress of anti-IgE treatment for allergic rhinitis. Am. J. Otolaryngol. 2025, 46, 104646. DOI: https://doi.org/10.1016/j.amjoto.2025.104646
    85. 85. Yamani, I.; Bu Saeed, K.; Alsulami, A.; et al. Efficacy of biologic therapies in the management of allergic rhinitis: A systematic review. Cureus 2024, 16, e71408. DOI: https://doi.org/10.7759/cureus.71408
    86. 86. Busse, W.W.; Maspero, J.F.; Lu, Y.; et al. Efficacy of dupilumab on clinical outcomes in patients with asthma and perennial allergic rhinitis. Ann. Allergy Asthma Immunol. 2020, 125, 565–576. DOI: https://doi.org/10.1016/j.anai.2020.05.026
    87. 87. Brooks, G.D. Updated evaluation of dupilumab in the treatment of asthma: patient selection and reported outcomes. Ther. Clin. Risk Manag. 2020, 16, 181–187. DOI: https://doi.org/10.2147/TCRM.S192392
    88. 88. Wipperman, M.F.; Gayvert, K.M.; Atanasio, A.; et al. Differential modulation of allergic rhinitis nasal transcriptome by dupilumab and allergy immunotherapy. Allergy 2024, 79, 894–907. DOI: https://doi.org/10.1111/all.16001
    89. 89. Tian, T.; Li, Y.; Yuan, G.; et al. Efficacy and safety of dupilumab in patients with moderate-to-severe atopic dermatitis and comorbid allergic rhinitis. Front. Med. 2025, 12, 1556769. DOI: https://doi.org/10.3389/fmed.2025.1556769
    90. 90. Huber, P.; Gröger, M.; Stihl, C.; et al. Diagnostics of allergic rhinitis under dupilumab therapy. Eur. Arch. Otorhinolaryngol. 2024, 281, 4183–4190. DOI: https://doi.org/10.1007/s00405-024-08700-2
    91. 91. Cheng, X.; Zhou, Y.; Hao, Y.; et al. Recent studies and prospects of biologics in allergic rhinitis treatment. Int. J. Mol. Sci. 2025, 26, 4509. DOI: https://doi.org/10.3390/ijms26104509
    92. 92. Thibaut de Ménonville, C.; Barakat, L.; Laborier, F.; et al. Efficacy of biologics for severe asthma on allergic comorbidities. Rev. Mal. Respir. 2024, 41, 669–679. DOI: https://doi.org/10.1016/j.rmr.2024.08.004
    93. 93. Corren, J.; Saini, S.S.; Gagnon, R.; et al. Short-term subcutaneous allergy immunotherapy and dupilumab are well tolerated in allergic rhinitis: A randomized trial. J. Asthma Allergy 2021, 14, 1045–1063. DOI: https://doi.org/10.2147/JAA.S318892
    94. 94. Zhang, Y.; Lan, F.; Zhang, L. Update on pathomechanisms and treatments in allergic rhinitis. Allergy 2022, 77, 3309–3319. DOI: https://doi.org/10.1111/all.15454
    95. 95. Adelowo, O.O.; Olisa, O.; Asekhame, O.T.; et al. Biotherapies in medical practice: A review and the Nigerian experience. West Afr. J. Med. 2021, 38, 486–493.
    96. 96. Shen, S.; Yan, B.; Wang, M.; et al. Stapokibart for severe uncontrolled chronic rhinosinusitis with nasal polyps: The CROWNS-2 randomized clinical trial. JAMA 2025, 334, 962–972. DOI: https://doi.org/10.1001/jama.2025.12515
    97. 97. Tajiri, T.; Suzuki, M.; Nishiyama, H.; et al. Efficacy of dupilumab for severe chronic rhinosinusitis with nasal polyps and asthma: A prospective study. Ann. Allergy Asthma Immunol. 2024, 133, 550–558. DOI: https://doi.org/10.1016/j.anai.2024.07.001
    98. 98. Bachert, C.; Khan, A.H.; Lee, S.E.; et al. Prevalence of type 2 inflammatory signatures and efficacy of dupilumab in patients with chronic rhinosinusitis with nasal polyps from two phase 3 clinical trials: SINUS-24 and SINUS-52. Int. Forum Allergy Rhinol. 2024, 14, 668–678. DOI: https://doi.org/10.1002/alr.23249
    99. 99. Tănase, M.I.; Tanase, M.; Cosgarea, M.; et al. Biologic treatments for chronic rhinosinusitis with nasal polyps: a comparative review of efficiency and risks. Cureus 2025, 17, e77804. DOI: https://doi.org/10.7759/cureus.77804
    100. 100. Kratchmarov, R.; Dharia, T.; Buchheit, K. Clinical efficacy and mechanisms of biologics for chronic rhinosinusitis with nasal polyps. J. Allergy Clin. Immunol. 2025, 155, 1401–1410. DOI: https://doi.org/10.1016/j.jaci.2025.03.011
    101. 101. Frankenberger, H.; Wiebringhaus, R.; Paul, B.; et al. The use of biologics in patients suffering from chronic rhinosinusitis with nasal polyps: A 4-year real-life observation. Eur. Arch. Otorhinolaryngol. 2024, 281, 5773–5782. DOI: https://doi.org/10.1007/s00405-024-08790-y
    102. 102. Chupp, G.; Alobid, I.; Lugogo, N.L.; et al. Mepolizumab reduces systemic corticosteroid use in chronic rhinosinusitis with nasal polyps. J. Allergy Clin. Immunol. Pract. 2023, 11, 3504–3512.e2. DOI: https://doi.org/10.1016/j.jaip.2023.08.015
    103. 103. Yang, S.K.; Cho, S.H.; Kim, D.W. Interpretation of clinical efficacy of biologics in chronic rhinosinusitis with nasal polyps via understanding the local and systemic pathomechanisms. Allergy Asthma Immunol. Res. 2022, 14, 465–478. DOI: https://doi.org/10.4168/aair.2022.14.5.465
    104. 104. Aldajani, A.; Alroqi, A.; Alromaih, S.; et al. Adverse events of biological therapy in chronic rhinosinusitis with nasal polyps: A systematic review. Am. J. Otolaryngol. 2022, 43, 103615. DOI: https://doi.org/10.1016/j.amjoto.2022.103615
    105. 105. Cai, S.; Xu, S.; Zhao, Y.; et al. Efficacy and safety of biologics for chronic rhinosinusitis with nasal polyps: A meta-analysis of real-world evidence. Allergy 2025, 80, 1256–1270. DOI: https://doi.org/10.1111/all.16499
    106. 106. Sim, L.; Md Shukri, N.; Yaacob, N.M.; et al. Efficacy and safety of dupilumab in chronic rhinosinusitis with nasal polyps: A systematic review and meta-analysis. Expert Rev. Clin. Pharmacol. 2025, 18, 211–224. DOI: https://doi.org/10.1080/17512433.2025.2468970
    107. 107. 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. Lancet Respir. Med. 2021, 9, 1141–1153. DOI: https://doi.org/10.1016/S2213-2600(21)00097-7
    108. 108. Cai, S.; Xu, S.; Lou, H.; et al. Comparison of different biologics for treating chronic rhinosinusitis with nasal polyps: A network analysis. J. Allergy Clin. Immunol. Pract. 2022, 10, 1876–1886.e7. DOI: https://doi.org/10.1016/j.jaip.2022.02.034
    109. 109. Chen, H.; Wang, L.; Zhang, J.; et al. Long-term efficacy and safety of different biologics in treatment of chronic rhinosinusitis with nasal polyps: A network meta-analysis. Braz. J. Otorhinolaryngol. 2025, 91, 101633. DOI: https://doi.org/10.1016/j.bjorl.2025.101633
    110. 110. De Corso, E.; Montuori, C.; Pipolo, C.; et al. Two-year turning point with dupilumab in chronic rhinosinusitis with nasal polyps: Control, remission, and tapering dosage. Allergy 2025, DOI: https://doi.org/10.1111/all.70032
    111. 111. Kiricsi, A.; Bella, Z.; Kraxner, H.; et al. Real-life effectiveness of dupilumab in chronic rhinosinusitis with nasal polyps: Results from eight Hungarian centres with 12-month follow-up. Rhinology 2024, 62, 410–420. DOI: https://doi.org/10.4193/Rhin23.278
    112. 112. Galletti, C.; Barbieri, M.A.; Ciodaro, F.; et al. Effectiveness and safety profile of dupilumab in chronic rhinosinusitis with nasal polyps: Real-life data in tertiary care. Pharmaceuticals 2023, 16, 630. DOI: https://doi.org/10.3390/ph16040630
    113. 113. Lin, Y.; Wang, W.; Zhu, Z.; et al. Adverse events for monoclonal antibodies in patients with allergic rhinitis: A systematic review and meta-analysis of randomized clinical trials. J. Clin. Med. 2023, 12, 2848. DOI: https://doi.org/10.3390/jcm12082848
    114. 114. Habenbacher, M.; Moser, U.; Hadl, O.; et al. Monoclonal antibody switching in biologic treatment of chronic rhinosinusitis with nasal polyps. J. Clin. Med. 2024, 13, 6883. DOI: https://doi.org/10.3390/jcm13226883
    115. 115. Brkic, F.F.; Liu, D.T.; Klimbacher, R.; et al. Efficacy and safety of switching between biologics in chronic rhinosinusitis with nasal polyps or N-ERD. Rhinology 2023, 61, 320–327. DOI: https://doi.org/10.4193/Rhin22.408
    116. 116. Crisci, C.D.; Ardusso, L.R.F. A precision medicine approach to rhinitis evaluation and management. Curr. Treat. Options Allergy 2020, 7, 93–109. DOI: https://doi.org/10.1007/s40521-020-00243-1
    117. 117. Breiteneder, H.; Peng, Y.Q.; Agache, I.; et al. Biomarkers for diagnosis and prediction of therapy responses in allergic diseases and asthma. Allergy 2020, 75, 3039–3068. DOI: https://doi.org/10.1111/all.14582
    118. 118. Okano, M.; Yamada, M.; Oka, A. Personalized medicine in chronic rhinosinusitis: Treatable traits using biologics for unmet needs. Allergy Asthma Immunol. Res. 2025, 17, 8–21. DOI: https://doi.org/10.4168/aair.2025.17.1.8
    119. 119. Maniu, A.A.; Perde-Schrepler, M.I.; Tatomir, C.B.; et al. Latest advances in chronic rhinosinusitis with nasal polyps endotyping and biomarkers, and their significance for daily practice. Rom. J. Morphol. Embryol. 2020, 61, 309–320. DOI: https://doi.org/10.47162/RJME.61.2.01
    120. 120. Li, J.; Mao, N.; Aodeng, S.; et al. Development and validation of an integrated deep learning model to assist eosinophilic chronic rhinosinusitis diagnosis: A multicenter study. Int. Forum Allergy Rhinol. 2025, 15, 1070–1081. DOI: https://doi.org/10.1002/alr.23595
    121. 121. Wang, K.; Ren, Y.; Ma, L.; et al. Explainable artificial intelligence predicts inflammatory and spatial heterogeneity from nasal polyp histology. J. Allergy Clin. Immunol. 2025, 156, 1573–1587. DOI: https://doi.org/10.1016/j.jaci.2025.08.016
    122. 122. Passali, D.; Bellussi, L.M.; Damiani, V.; et al. Chronic rhinosinusitis with nasal polyposis: The role of personalized and integrated medicine. Acta Biomed. 2020, 91, 11–18. DOI: https://doi.org/10.23750/abm.v91i1-S.9243
    123. 123. Macchi, A.; Giorli, A.; Cantone, E.; et al. Sense of smell in chronic rhinosinusitis: A multicentric study on 811 patients. Front. Allergy 2023, 4, 1083964. DOI: https://doi.org/10.3389/falgy.2023.1083964
    124. 124. Papapostolou, N.; Makris, M. Allergic asthma in the era of personalized medicine. J. Pers. Med. 2022, 12, 1162. DOI: https://doi.org/10.3390/jpm12071162
    125. 125. Kim, C.K.; Callaway, Z.; Pawankar, R. Eosinophil granule proteins as a biomarker in managing asthma and allergies. Asia Pac. Allergy 2023, 13, 66–71. DOI: https://doi.org/10.5415/apallergy.0000000000000104
    126. 126. Fokkens, W.; van der Lans, R.; Reitsma, S. Dupilumab for the treatment of chronic rhinosinusitis with nasal polyposis. Expert Opin. Biol. Ther. 2021, 21, 575–585. DOI: https://doi.org/10.1080/14712598.2021.1901881
    127. 127. Takahashi, H.; Matsuyama, T.; Kawabata-Iwakawa, R.; et al. Comprehensive profiling of the heterogeneity of molecular endotypic traits in chronic rhinosinusitis. Hum. Immunol. 2025, 86, 111267. DOI: https://doi.org/10.1016/j.humimm.2025.111267
    128. 128. Loperfido, A.; Cavaliere, C.; Fionda, B.; et al. The emerging role of microRNAs in nasal inflammatory diseases and tumors: From bench to bedside. Genes 2025, 16, 295. DOI: https://doi.org/10.3390/genes16030295
    129. 129. Lai, S.; Kang, W.; Chen, Y.; et al. An End-to-End CRSwNP Prediction with Multichannel ResNet on Computed Tomography. Int. J. Biomed. Imaging 2024, 2024, 4960630. DOI: https://doi.org/10.1155/2024/4960630
    130. 130. Mishra, T.; Sasanka, K.K.; Sudha Ty, S.; et al. Emerging novel biomarkers in allergic rhinitis: A narrative review. Cureus 2025, 17, e84705. DOI: https://doi.org/10.7759/cureus.84705
    131. 131. Narasimhan, G.; Deshmukh, P.T.; Gaurkar, S.S.; et al. A comprehensive review exploring allergic rhinitis with nasal polyps: Mechanisms, management, and emerging therapies. Cureus 2024, 16, e59191. DOI: https://doi.org/10.7759/cureus.59191
    132. 132. Bachert, C.; Zhang, N.; Cavaliere, C.; et al. Biologics for chronic rhinosinusitis with nasal polyps. J. Allergy Clin. Immunol. 2020, 145, 725–739. DOI: https://doi.org/10.1016/j.jaci.2020.01.020
    133. 133. Jin, Z.; Yan, B.; Zhang, L.; et al. Biological therapy in chronic rhinosinusitis with nasal polyps. Expert Rev. Clin. Immunol. 2025, 21, 473–492. DOI: https://doi.org/10.1080/1744666X.2025.2459929
    134. 134. Bachert, C.; Desrosiers, M.Y.; Hellings, P.W.; et al. The role of biologics in chronic rhinosinusitis with nasal polyps. J. Allergy Clin. Immunol. Pract. 2021, 9, 1099–1106. DOI: https://doi.org/10.1016/j.jaip.2020.11.017
    135. 135. Dorling, M.; Sarafan, M.; Voizard, B.; et al. Switching biologics in chronic rhinosinusitis with nasal polyps: A multicenter Canadian experience. Int. Forum Allergy Rhinol. 2025, 15, 166–173. DOI: https://doi.org/10.1002/alr.23466
    136. 136. Peters, A.; Zhao, X.; Near, A.M.; et al. Real-world outcomes following biologic initiation in US patients with chronic rhinosinusitis with nasal polyps. Adv. Ther. 2025, 42, 1783–1799. DOI: https://doi.org/10.1007/s12325-025-03120-y
    137. 137. Borish, L.; Cohen, N.A.; Chupp, G.; et al. Evaluating enrollment and outcome criteria in trials of biologics for chronic rhinosinusitis with nasal polyps. Ann. Allergy Asthma Immunol. 2022, 129, 160–168. DOI: https://doi.org/10.1016/j.anai.2022.04.004
    138. 138. Luk, H.G.; Janz, T.A.; Siddiqui, F.N.; et al. Considerations for the use of biologics in chronic rhinosinusitis with nasal polyps. Ear Nose Throat J. 2025. DOI: https://doi.org/10.1177/01455613251363018
    139. 139. Xian, M.; Yan, B.; Song, X.; et al. Chinese position paper on biologic therapy for chronic rhinosinusitis with nasal polyps. Allergy 2025, 80, 1208–1225. DOI: https://doi.org/10.1111/all.16519
    140. 140. Guo, C.L.; Liu, F.F.; Wang, D.Y.; et al. Type 2 Biomarkers for the Indication and Response to Biologics in CRSwNP. Curr. Allergy Asthma Rep. 2023, 23, 703–713. DOI: https://doi.org/10.1007/s11882-023-01114-w
    141. 141. Alharbi, T.; Alsubaie, N.; Alroqi, A. An overview of switching biological therapies for chronic rhinosinusitis with nasal polyposis. Eur. Arch. Otorhinolaryngol. 2025, 282, 6057–6068. DOI: https://doi.org/10.1007/s00405-025-09559-7
    142. 142. Blaiss, M.S. Chronic rhinosinusitis with nasal polyps management in the age of biologics. Allergy Asthma Proc. 2020, 41, 413–419. DOI: https://doi.org/10.2500/aap.2020.41.200069
    143. 143. Favier, V.; Daveau, C.; Carsuzaa, F.; et al. Study protocol: The biologics in severe chronic rhinosinusitis with nasal polyps survey. BMJ Open 2024, 14, e083112. DOI: https://doi.org/10.1136/bmjopen-2023-083112
    144. 144. Seidel, D.U.; Busenius, J.; Below, M.; et al. Prescriptions of biologics in patients with chronic rhinosinusitis with nasal polyps in Germany (2019–2023). Eur. Arch. Otorhinolaryngol. 2025, 282, 5711–5720. DOI: https://doi.org/10.1007/s00405-025-09742-w
    145. 145. Roland, L.T.; Regenberg, A.; Luong, A.U.; et al. Biologics for chronic rhinosinusitis with nasal polyps: Economics and ethics. Int. Forum Allergy Rhinol. 2021, 11, 1524–1528. DOI: https://doi.org/10.1002/alr.22864
    146. 146. Xian, M.; Wang, C.; Zhang, L. Regional disparities in cost-effectiveness of biologics for CRSwNP warrant tailored treatment strategies. Rhinology 2025, DOI: https://doi.org/10.4193/Rhin25.291
    147. 147. Eschenbacher, W.; Straesser, M.; Knoeddler, A.; et al. Biologics for the treatment of allergic rhinitis, chronic rhinosinusitis, and nasal polyposis. Immunol. Allergy Clin. North Am. 2020, 40, 539–547. DOI: https://doi.org/10.1016/j.iac.2020.06.001
    148. 148. van der Lans, R.J.L.; Hopkins, C.; Senior, B.A.; et al. Biologicals and endoscopic sinus surgery for severe uncontrolled chronic rhinosinusitis with nasal polyps: An economic perspective. J. Allergy Clin. Immunol. Pract. 2022, 10, 1454–1461. DOI: https://doi.org/10.1016/j.jaip.2022.02.017
    149. 149. Chapurin, N.; Khan, S.; Gutierrez, J.; et al. Economics of medical and surgical management of chronic rhinosinusitis with nasal polyps: A contemporary review. Am. J. Rhinol. Allergy 2023, 37, 227–231. DOI: https://doi.org/10.1177/19458924221147501
    150. 150. Eriksen, P.R.G.; Jakobsen, K.K.; Aanæs, K.; et al. The potential role of biological treatment of chronic rhinosinusitis with nasal polyps: A nationwide cohort study. Rhinology 2021, 59, 374–379. DOI: https://doi.org/10.4193/Rhin20.480
    151. 151. Liu, L.; Zhang, S.; Zhao, Z. Expert Recommendations on Graded Prevention of Allergic Rhinitis. Zhonghua Yu Fang Yi Xue Za Zhi 2025, 59, 766–779. DOI: https://doi.org/10.3760/cma.j.cn112150-20250307-00183
    152. 152. Schneider, A.L.; Schleimer, R.P.; Tan, B.K. Targetable pathogenic mechanisms in nasal polyposis. Int. Forum Allergy Rhinol. 2021, 11, 1220–1234. DOI: https://doi.org/10.1002/alr.22787
    153. 153. Sarnoch, S.O.; Pepić, A.; Schmitz, L.; et al. The value of biomarkers in the therapy of chronic rhinosinusitis with nasal polyps with biologicals: A long-term follow-up of dupilumab therapy. Eur. Arch. Otorhinolaryngol. 2024, 281, 4789–4805. DOI: https://doi.org/10.1007/s00405-024-08574-4
    154. 154. Weissman, B.; Shen, K.; Flanagan, O.L.; et al. Comparing medical and surgical management of chronic rhinosinusitis: A systematic review of dupilumab and endoscopic sinus surgery. Cureus 2025, 17, e79742. DOI: https://doi.org/10.7759/cureus.79742
    155. 155. Wang, M.; Li, Y.; Li, J.; et al. New insights into the endotypes of chronic rhinosinusitis in the biologic era. J. Allergy Clin. Immunol. 2025, 156, 51–60. DOI: https://doi.org/10.1016/j.jaci.2025.02.015
    156. 156. Chufistova, A.V.; Shabaldina, E.V.; Bedareva, A.V.; et al. Features of inflammatory endotypes and phenotypes in chronic rhinosinusitis. Vestn. Otorinolaringol. 2024, 89, 60–67. DOI: https://doi.org/10.17116/otorino20248904160
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