Kim Jean, Naclerio Robert
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Medicine: Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ther Clin Risk Manag. 2020 Jan 23;16:31-37. doi: 10.2147/TCRM.S210648. eCollection 2020.
Chronic rhinosinusitis with nasal polyposis (CRSwNP) is one of the most severe forms of chronic rhinosinusitis. CRSwNP is characterized by nasal and facial congestion, loss of sense of smell, rhinorrhea, and post-nasal drip. Treatments have been ineffective at controlling disease recurrence, despite multiple courses of medical and surgical therapies. Oral glucocorticoid therapy is often used to control exacerbations leaving the patient exposed to steroid-induced adverse effects. Thus, there is a clear unmet need for new treatments to achieve better control of the disease. Advances in understanding Type 2 inflammatory processes that occur in about 80% of the Western world patients with CRSwNP have resulted in new avenues for disease control. Biologics in the form of monoclonal antibodies, which target Type 2 inflammation, have helped control the severest forms of atopic dermatitis and asthma. Treatment regimes for CRSwNP now include biologics. In July 2019, dupilumab was the first monoclonal antibody to gain FDA approval for the treatment of CRSwNP. In this review, we summarize the proof of concept clinical trials and Phase 3 trials leading to approval of dupilumab, an anti-IL4 alpha receptor antagonist that blocks the actions of both IL4 and IL13. These studies show that dupilumab is a proven treatment option to control disease. Collective studies demonstrate a high safety profile. Questions arise as to the best use of dupilumab in the context of current treatment paradigms, and for which sub-population of the varied heterogeneous endotypes of CRSwNP patients. Recognizing the high cost of biologics forces the need for cost-effectiveness analysis.
伴鼻息肉的慢性鼻窦炎（CRSwNP）是慢性鼻窦炎最严重的形式之一。CRSwNP的特征为鼻面部充血、嗅觉丧失、鼻溢液和鼻后滴漏。尽管进行了多疗程的药物和手术治疗，但这些治疗在控制疾病复发方面均无效。口服糖皮质激素治疗常用于控制病情加重，但会使患者面临类固醇诱导的不良反应。因此，显然迫切需要新的治疗方法来更好地控制该疾病。对约80%的西方CRSwNP患者中发生的2型炎症过程认识的进展，为疾病控制带来了新途径。以单克隆抗体形式存在的生物制剂，靶向2型炎症，已有助于控制最严重形式的特应性皮炎和哮喘。CRSwNP的治疗方案现在包括生物制剂。2019年7月，度普利尤单抗是首个获得美国食品药品监督管理局（FDA）批准用于治疗CRSwNP的单克隆抗体。在本综述中，我们总结了导致度普利尤单抗获批的概念验证临床试验和3期试验，度普利尤单抗是一种抗IL4α受体拮抗剂，可阻断IL4和IL13的作用。这些研究表明度普利尤单抗是一种经证实的控制疾病的治疗选择。多项研究证明其具有较高的安全性。在当前治疗模式背景下，对于CRSwNP患者不同异质内型的哪些亚群，度普利尤单抗的最佳使用方式存在疑问。认识到生物制剂的高成本促使需要进行成本效益分析。
