Department of Otolaryngology/Head and Neck Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Division of Rhinology, Allergy and Endoscopic Skull Base Surgery, The University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC, 27599-7070, USA.
J Otolaryngol Head Neck Surg. 2023 Sep 28;52(1):64. doi: 10.1186/s40463-023-00668-z.
Dupilumab and other biologics have revolutionized the management of recalcitrant polyps in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP). Despite strong evidence for the efficacy of dupilumab in treating polyps, factors such as cost and uncertain efficacy over surgery have limited its use to patients who have failed the use of topical nasal steroids and initial surgical management. Likewise, the use of this drug is often directed towards patients with greater polyp burdens. Recent studies, however, have investigated the use of dupilumab and other biologics in expanded patient populations, including those with limited polyp burden. The overall trend in the literature suggests a future move towards the use of biologics as first-line therapy for all patients with CRSwNP. The arguments against widespread, routine use of dupilumab and biologics in all patients with CRSwNP are threefold. First, endoscopic sinus surgery has been found to provide similar symptomatic benefit to dupilumab in the treatment of these patient populations. The surgical improvement of patients' sinonasal anatomy offers a rapid elimination of sources of ongoing inflammation that contribute to long-term polyp formation and symptoms. Medical non-compliance in this specific patient population is known to be an issue, with surgery offering a much greater long-term prospect of symptomatic relief in non-compliant patients. The second concern revolves around the potential for side effects of dupilumab and other biologics. Initial studies have shown an acceptable safety profile, but trials assessing the use of dupilumab for a separate indication revealed a higher rate of conjunctivitis. Long-term safety data is limited for biologics, and we must be prepared for the possibility of severe, unanticipated adverse events in the future. Our third and most profound concern is the significant cost of dupilumab. This medication is enormously expensive, and all current literature suggests that treatment would need to be life-long to remain effective. Studies comparing endoscopic sinus surgery to various biologics, including dupilumab, have shown comparable overall quality of life metrics with biologics, all while delivering considerably higher anticipated lifetime costs. As our knowledge progresses regarding the efficacy of dupilumab and other biologics in a variety of clinic situations, it is important to understand the context in which these advances are being made. While dupilumab and other biologics offer undeniable efficacy in the treatment of chronic rhinosinusitis with nasal polyposis which has failed to respond to standard therapies, we argue that biologics remain only a component of effective management in this patient population. Endoscopic sinus surgery and topical nasal steroids offer equal efficacy and substantially lower costs than biologics, and these factors should be considered when selecting treatment options for patients.
度普利尤单抗和其他生物制剂彻底改变了慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）患者中顽固息肉的治疗方法。尽管有强有力的证据表明度普利尤单抗治疗息肉有效，但由于成本和手术效果不确定等因素，其仅被用于那些已经使用局部鼻腔类固醇和初始手术治疗失败的患者。同样，该药的使用通常针对息肉负担较大的患者。然而，最近的研究已经调查了在更广泛的患者群体中使用度普利尤单抗和其他生物制剂，包括那些息肉负担有限的患者。文献中的总体趋势表明，将来可能会将生物制剂作为所有 CRSwNP 患者的一线治疗药物。反对在所有 CRSwNP 患者中广泛常规使用度普利尤单抗和生物制剂的论点有三。首先，内镜鼻窦手术已被发现与这些患者群体中的度普利尤单抗治疗一样，可提供类似的症状改善。手术改善患者鼻窦解剖结构，迅速消除导致长期息肉形成和症状的持续炎症源。已知该特定患者群体存在医疗不合规问题，手术为不合规患者提供了更大的长期症状缓解前景。第二个担忧是度普利尤单抗和其他生物制剂的潜在副作用。初步研究表明其安全性可接受，但评估度普利尤单抗用于另一种适应症的试验显示，结膜炎发生率更高。生物制剂的长期安全性数据有限，我们必须为未来可能出现严重的、意料之外的不良事件做好准备。我们最关心的第三个问题是度普利尤单抗的高昂费用。这种药物非常昂贵，所有现有文献都表明，为了保持疗效，治疗需要终身进行。将内镜鼻窦手术与各种生物制剂（包括度普利尤单抗）进行比较的研究表明，与生物制剂相比，两者的总体生活质量指标相当，而生物制剂的预期终生成本要高得多。随着我们对度普利尤单抗和其他生物制剂在各种临床情况下的疗效的了解不断深入，了解这些进展的背景非常重要。虽然度普利尤单抗和其他生物制剂在治疗对标准治疗无反应的慢性鼻-鼻窦炎伴鼻息肉方面具有不可否认的疗效，但我们认为生物制剂仍然只是该患者群体有效管理的一个组成部分。内镜鼻窦手术和局部鼻腔类固醇的疗效与生物制剂相当，但成本要低得多，在为患者选择治疗方案时应考虑这些因素。
