Department of Surgery, The University of Auckland, Auckland, New Zealand.
Department of Otolaryngology Head and Neck Surgery, The Queen Elizabeth Hospital, Woodville South, South Australia.
Int Forum Allergy Rhinol. 2019 Apr;9(4):378-387. doi: 10.1002/alr.22288. Epub 2019 Jan 15.
Chronic rhinosinusitis (CRS) patients who fail medical management have few treatment options other than endoscopic sinus surgery (ESS). A novel biodegradable mometasone furoate drug delivery system (LYR-210) providing continuous topical steroid therapy to sinonasal mucosa over 24 weeks was developed to treat unoperated CRS patients who have failed medical management prior to ESS. LYR-210 was designed to slowly expand in the middle meatus, ensuring efficient drug delivery as mucosal swelling reduces.
A prospective, multicenter, open-label study was conducted in 20 CRS subjects who were determined to be candidates for ESS. Under endoscopic guidance and topical anesthesia, LYR-210 was placed in both middle meatuses. The primary endpoint was product-related serious adverse events (SAEs) at 4 weeks. Additional assessments included plasma drug concentration, morning serum cortisol levels, intraocular pressures (IOPs), and Sino-Nasal Outcome Test (SNOT-22) scores.
LYR-210 was successfully placed bilaterally in 20 subjects (12 without nasal polyps and 8 with polyps) in an office setting. There were no product-related SAEs through 24 weeks, at which point 86% of LYR-210 depots were still retained in the middle meatus. Serum cortisol, IOP, and plasma drug concentrations supported systemic safety at all time points tested. Subjects experienced significant reductions in their SNOT-22 scores as early as week 1, and this reduction persisted through week 24 (p < 0.01). Significant symptom improvement was achieved in the SNOT-22 rhinologic, extranasal rhinologic, ear-facial, psychological, and sleep dysfunction subdomains at 24 weeks (p < 0.05).
LYR-210 is safe and well-tolerated in ESS-naive CRS patients and leads to sustained symptom improvement in patients.
慢性鼻-鼻窦炎（CRS）患者在药物治疗失败后，除了内镜鼻窦手术（ESS）外，治疗选择有限。一种新型可生物降解糠酸莫米松药物递送系统（LYR-210）被开发出来，用于治疗未经手术的 CRS 患者，这些患者在接受 ESS 之前已经对药物治疗失败。LYR-210 设计为在中鼻甲缓慢扩张，以确保在黏膜肿胀减少时有效递送药物。
在 20 名被确定为 ESS 候选者的 CRS 受试者中进行了一项前瞻性、多中心、开放标签研究。在内镜引导和局部麻醉下，将 LYR-210 放置在双侧中鼻甲。主要终点是 4 周时与产品相关的严重不良事件（SAE）。其他评估包括血浆药物浓度、清晨血清皮质醇水平、眼内压（IOP）和鼻-鼻窦炎结局测试（SNOT-22）评分。
LYR-210 在 20 名受试者（12 名无鼻息肉和 8 名有息肉）的办公室环境中双侧成功放置。在 24 周时，没有与产品相关的 SAE，此时 86%的 LYR-210 储库仍保留在中鼻甲。在所有测试时间点，血清皮质醇、IOP 和血浆药物浓度均支持全身安全性。受试者在第 1 周就出现了 SNOT-22 评分的显著降低，这种降低一直持续到第 24 周（p<0.01）。在 24 周时，SNOT-22 的鼻科学、鼻外科学、耳面部、心理和睡眠功能障碍子领域的症状显著改善（p<0.05）。
LYR-210 在 ESS 初治 CRS 患者中安全且耐受良好，并能持续改善患者的症状。
