Sindwani Raj, Han Joseph K, Soteres Daniel F, Messina John C, Carothers Jennifer L, Mahmoud Ramy A, Djupesland Per G
1 Head and Neck Institute, Cleveland Clinic, Cleveland, Ohio.
2 Department of Otolaryngology, Head & Neck Surgery, Eastern Virginia Medical School, Norfolk, Virginia.
Am J Rhinol Allergy. 2019 Jan;33(1):69-82. doi: 10.1177/1945892418810281. Epub 2018 Nov 27.
Chronic rhinosinusitis is a common, high-morbidity chronic inflammatory disease, and patients often experience suboptimal outcomes with current medical treatment. The exhalation delivery system with fluticasone (EDS-FLU) may improve care by increasing superior/posterior intranasal corticosteroid deposition.
To evaluate the efficacy and safety of EDS-FLU versus EDS-placebo in patients with nasal polyps (NP). Coprimary end points were change in nasal congestion and polyp grade. Key secondary end points were Sino-Nasal Outcome Test-22 (SNOT-22) and Medical Outcomes Study Sleep Scale-Revised (MOS Sleep-R). Other prespecified end points included all 4 cardinal symptoms of NP, 36-Item Short Form Health Survey (SF-36), Patient Global Impression of Change (PGIC), Rhinosinusitis Disability Index (RSDI), and key indicators for surgical intervention.
Randomized, double-blind, EDS-placebo-controlled, multicenter study.
Three hundred twenty-three subjects with NP and moderate-severe congestion/obstruction, most with history of corticosteroid use (94.4%) and/or prior surgery (60.4%), were randomized to EDS-FLU 93 µg, 186 µg, or 372 µg or EDS-placebo twice daily (BID) for 24 weeks (16 double-blind + 8 single-arm extension with EDS-FLU 372 µg BID).
All EDS-FLU doses produced significant improvement in both coprimary end points ( P < .05) and in SNOT-22 total score ( P ≤ .005). EDS-FLU significantly improved all 4 cardinal symptoms of NP ( P < .05), including congestion/obstruction, facial pain/pressure, rhinorrhea/post-nasal drip, and hyposmia/anosmia. Approximately 80% of subjects reported improvement with EDS-FLU, with 65% reporting "much" or "very much" improvement by week 16. Adverse events were generally local in nature and similar to other intranasal steroids studied for similar durations in similar populations, with the most common being epistaxis.
In patients with chronic rhinosinusitis with NP (CRSwNP) who were symptomatic despite high rates of prior intranasal steroid use and/or surgery, EDS-FLU produced statistically significant and clinically meaningful improvements compared to EDS-placebo in multiple subjective and objective outcomes (symptoms, SNOT-22, RSDI, SF-36, PGIC, and NP grade), including all 4 cardinal symptoms of CRSwNP.
慢性鼻-鼻窦炎是一种常见的、高发病率的慢性炎症性疾病，目前的药物治疗往往使患者的治疗效果欠佳。含氟替卡松的呼气给药系统（EDS-FLU）可能通过增加鼻内皮质类固醇在鼻腔上部/后部的沉积来改善治疗效果。
评估EDS-FLU与EDS-安慰剂治疗鼻息肉（NP）患者的疗效和安全性。共同主要终点为鼻塞和息肉分级的变化。关键次要终点为鼻窦-鼻腔结局测试-22（SNOT-22）和医学结局研究睡眠量表修订版（MOS睡眠-R）。其他预先设定的终点包括NP的所有4种主要症状、简明健康状况调查36项量表（SF-36）、患者总体印象变化（PGIC）、鼻-鼻窦炎残疾指数（RSDI）以及手术干预的关键指标。
随机、双盲、EDS-安慰剂对照、多中心研究。
323例患有NP且有中重度充血/阻塞的受试者，大多数有皮质类固醇使用史（94.4%）和/或既往手术史（60.4%），被随机分为每日两次（BID）使用93μg、186μg或372μg的EDS-FLU或EDS-安慰剂，持续24周（16周双盲+8周单臂延长期，使用372μg BID的EDS-FLU）。
所有EDS-FLU剂量在两个共同主要终点（P＜0.05）和SNOT-22总分（P≤0.005）方面均产生了显著改善。EDS-FLU显著改善了NP的所有4种主要症状（P＜0.05），包括充血/阻塞、面部疼痛/压迫感、流涕/后鼻滴漏以及嗅觉减退/嗅觉丧失。约80%的受试者报告使用EDS-FLU后症状改善，65%的受试者在第16周时报告“明显”或“非常明显”改善。不良事件一般为局部性，与在类似人群中进行类似时长研究的其他鼻内类固醇相似，最常见的是鼻出血。
在尽管先前鼻内使用类固醇和/或手术比例较高但仍有症状的慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）患者中，与EDS-安慰剂相比，EDS-FLU在多个主观和客观结局（症状、SNOT-22、RSDI、SF-36、PGIC和NP分级）方面产生了具有统计学意义和临床意义的改善，包括CRSwNP的所有4种主要症状。
