Department of Specialist Allergy and Clinical Immunology, Royal National ENT Hospital, University College London Hospitals NHS Foundation Trust, London, UK.
Department of Rhinology, Royal National ENT Hospital, University College London Hospitals NHS Foundation Trust, London, UK.
Drug Des Devel Ther. 2020 May 8;14:1757-1769. doi: 10.2147/DDDT.S243053. eCollection 2020.
In September 2019, published details of two large Phase III double-blind placebo-controlled studies (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52) confirming the clinical efficacy of the biologic dupilumab in simultaneously blocking both IL-4/IL-13 signalling in chronic rhinosinusitis with nasal polyps (CRSwNP). The studies demonstrated that dupilumab (Dupixent, Sanofi and Regeneron) 300mg subcutaneously administered was clinically effective when added for patients with moderate to severe CRSwNP already maintained on the standard intranasal steroid mometasone furoate. Duration of treatment ranged from injections either 2 weekly for 24 weeks (SINUS-24) or every 2 weeks for 52 weeks or finally every 2 weeks for 24 weeks stepping down thereafter to every 4 weeks for a further 28 weeks (SINUS-52). Rapid improvements in all important parameters of disease burden were seen with such improvement maintained even where the frequency of injections was decreased. In patients with co-existent asthma, lung function and asthma control scores improved. This is consistent with the one airway hypothesis of shared T2 inflammatory programmes driving both disease syndromes. The studies formed the basis for FDA registration and clinical launch in the US, and EMA approval in Europe. Dupilumab presents a significant new treatment option in an area of urgent unmet therapeutic need in CRSwNP. Should dupilumab prove to be as effective in the real-life clinical environment as it has been in the studies, then a paradigm shift from sinonasal surgery to medical treatment of CRSwNP may need to occur in the ENT community. Questions in relation to best patient selection, combined upper and lower airway therapeutic pathways, long-term safety along with health economics and cost constraints ought now to be addressed.
2019 年 9 月，[公司名称]公布了两项大型 III 期双盲安慰剂对照研究（LIBERTY NP SINUS-24 和 LIBERTY NP SINUS-52）的详细结果，证实了生物制剂度普利尤单抗在同时阻断慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）患者中 IL-4/IL-13 信号通路的临床疗效。这些研究表明，皮下注射 300mg 度普利尤单抗（Dupixent，赛诺菲和再生元）对已接受标准鼻腔内皮质类固醇糠酸莫米松治疗的中重度 CRSwNP 患者具有临床疗效。治疗持续时间从每 2 周注射 24 周（SINUS-24）到每 2 周注射 52 周，或者每 2 周注射 24 周，然后降至每 4 周注射 28 周（SINUS-52）。所有疾病负担的重要参数都迅速改善，即使减少注射频率，这种改善仍能维持。在合并哮喘的患者中，肺功能和哮喘控制评分得到改善。这与共同气道假说一致，即 T2 炎症程序驱动这两种疾病综合征。这些研究为 FDA 注册和美国的临床启动以及欧洲 EMA 的批准提供了依据。度普利尤单抗在 CRSwNP 治疗领域中迫切需要满足的未满足的治疗需求方面提供了一种重要的新治疗选择。如果度普利尤单抗在真实临床环境中像研究中那样有效，那么 ENT 社区可能需要从鼻-鼻窦手术向 CRSwNP 的药物治疗转变。现在应该解决与最佳患者选择、上下气道联合治疗途径、长期安全性以及卫生经济学和成本限制相关的问题。
