Department of Surgery, College of Medicine, University of Vermont, Burlington, Vt.
Bellingham Asthma, Allergy and Immunology Clinic, Bellingham, Wash.
J Allergy Clin Immunol. 2019 Jan;143(1):126-134.e5. doi: 10.1016/j.jaci.2018.06.010. Epub 2018 Jun 19.
Chronic rhinosinusitis is common and sometimes complicated by nasal polyps (NPs). Corticosteroid nasal sprays are often unsatisfactory because they are ineffective at delivering medication to high/deep sites of inflammation.
We sought to assess whether an exhalation delivery system with fluticasone (EDS-FLU) capable of high/deep drug deposition improves outcomes.
Patients (n = 323) 18 years and older with moderate-to-severe congestion and NPs were randomized to twice-daily EDS-FLU (93, 186, or 372 μg) or exhalation delivery system (EDS)-placebo for 24 weeks (16 double-blind plus 8 open-label when all received 372 μg). Coprimary end points were change in nasal congestion/obstruction at 4 weeks and summed bilateral polyp grade at 16 weeks. Secondary end points included symptoms, polyp elimination, and functioning.
EDS-FLU was superior on both coprimary end points (P < .001 vs EDS-placebo, all doses). Mean polyp grade improved continuously through week 24 (P < .009, all comparisons), with polyps eliminated on at least 1 side in approximately 25% of patients at week 24 versus 8.7% with EDS-placebo (P ≤ .014, all comparisons). Sino-Nasal Outcomes Test scores also improved significantly versus those in patients receiving EDS-placebo (-21.1 to -21.4 vs -11.7 at week 16, P < .05 all doses). At the end of the double-blind period, EDS-FLU (all doses) significantly improved all 4 defining disease symptoms. In most patients (68%), those receiving EDS-FLU reported "much" or "very much" improvement. The number of patients eligible for surgery decreased by 62%-67%. The safety profile was similar to that reported in prior trials evaluating conventional corticosteroid nasal sprays in comparable populations.
EDS-FLU produces clinically and statistically significant improvement in all 4 diagnostically defining disease symptoms, polyp grade, and quality of life in patients with chronic rhinosinusitis with NPs.
慢性鼻-鼻窦炎较为常见，有时会并发鼻息肉（NPs）。皮质类固醇鼻腔喷雾剂通常效果不佳，因为它们无法将药物递送到炎症的高/深部位置。
我们旨在评估是否可以使用能够实现高/深部药物沉积的氟替卡松呼气输送系统（EDS-FLU）来改善结果。
18 岁及以上患有中度至重度鼻塞和鼻息肉的患者被随机分为每日两次 EDS-FLU（93、186 或 372μg）或呼气输送系统（EDS）-安慰剂组，疗程为 24 周（16 周双盲加 8 周开放标签，所有患者均接受 372μg）。主要终点是治疗 4 周时的鼻腔充血/阻塞变化和治疗 16 周时双侧息肉的总和分级。次要终点包括症状、息肉消除和功能。
EDS-FLU 在两个主要终点上均优于 EDS-安慰剂（均 P<.001）。通过第 24 周，息肉分级持续改善（P<.009，所有比较），大约 25%的患者在第 24 周时至少有一侧的息肉消除，而 EDS-安慰剂组为 8.7%（所有比较 P≤.014）。与接受 EDS-安慰剂的患者相比，Sino-Nasal Outcomes Test 评分也显著改善（第 16 周时分别为-21.1 至-21.4 分和-11.7 分，所有剂量 P<.05）。在双盲期结束时，EDS-FLU（所有剂量）显著改善了所有 4 项定义疾病症状。在大多数患者（68%）中，接受 EDS-FLU 的患者报告“非常”或“非常非常”改善。有资格接受手术的患者数量减少了 62%-67%。安全性概况与先前在类似人群中评估常规皮质类固醇鼻腔喷雾剂的试验报告相似。
EDS-FLU 可显著改善慢性鼻-鼻窦炎伴鼻息肉患者的所有 4 项诊断定义疾病症状、息肉分级和生活质量。
