Eye Research Foundation, Newport Beach, California.
Andover Eye Associates, Andover, Massachusetts.
Ophthalmology. 2019 Jun;126(6):792-800. doi: 10.1016/j.ophtha.2019.01.024. Epub 2019 Jan 28.
To compare the efficacy, safety, and tolerability of waterfree cyclosporine formulation (CyclASol) at 2 concentrations (0.1% and 0.05% of cyclosporine [CsA]) to vehicle when applied twice daily for 16 weeks in patients with dry eye disease (DED). An open-label Restasis (Allergan, Irvine, CA) arm was included to allow a direct comparison with an approved therapy.
An exploratory phase II, multicenter, randomized, vehicle-controlled clinical trial, double-masked between CyclASol and vehicle with an open-label comparator.
Two hundred and seven eligible patients with a history of dry eye disease were randomized 1:1:1:1 to 1 of 4 treatment arms (CyclASol 0.05%, n = 51; CyclASol 0.1%, n = 51; vehicle, n = 52, and Restasis, n = 53).
After a 2-week run-in period with twice-daily dosing of Systane Balance (Alcon, Fort Worth, TX), patients were randomized to the respective treatment arm and dosed twice daily for 16 weeks.
The study was set up to explore efficacy on a number of sign and symptom end points including total and subregion corneal fluorescein staining, conjunctival staining, visual analog scale (VAS) for dry eye symptoms VAS severity, and Ocular Surface Disease Index (OSDI) questionnaire.
CyclASol showed a consistent reduction in corneal and conjunctival staining compared with both vehicle and Restasis over the 16-week treatment period, with an early onset of effect (at day 14). A mixed-effects model-based approach demonstrated that the CyclASol drug effect was statistically significant over vehicle (total corneal staining P < 0.1, central corneal staining P < 0.001, conjunctival staining P < 0.01). This model-based analysis suggests a significant CyclASol effect for OSDI as symptom parameter (P < 0.01). The numbers of ocular adverse events were low in all treatment groups.
CyclASol showed efficacy, safety, and tolerability at 2 concentrations in moderate-to-severe DED. In a direct head-to-head against open-label Restasis, CyclASol was found to have an earlier onset of action, as early as after 2 weeks of treatment, in relieving the signs of DED, as measured by corneal and conjunctival staining. The central region of the cornea, an important area for visual function in dry eye sufferers, was shown to have the most benefit from treatment. Excellent safety, tolerability, and comfort profile supports this new CsA formulation as having a positive benefit-to-risk ratio.
比较水飞蓟素制剂（CyclASol）在 2 种浓度（环孢素 0.1%和 0.05%）与载体在每日 2 次使用 16 周后，在患有干眼症（DED）的患者中的疗效、安全性和耐受性。还纳入了开放性标签的 Restasis（Allergan，加利福尼亚州欧文）手臂，以允许与已批准的疗法进行直接比较。
这是一项探索性的 II 期、多中心、随机、双盲的安慰剂对照临床试验，CyclASol 与载体之间双盲，开放性标签的对照。
207 名符合条件的干眼症患者，按 1：1：1：1 的比例随机分为 4 个治疗组（CyclASol 0.05%，n=51；CyclASol 0.1%，n=51；载体，n=52，和 Restasis，n=53）。
在使用 Systane Balance（Alcon，德克萨斯州沃思堡）进行 2 周的双盲治疗后，患者被随机分配到各自的治疗组，并接受 16 周的每日 2 次剂量。
该研究旨在探索多种体征和症状终点的疗效，包括总角膜和结膜荧光素染色、结膜染色、干眼症状的视觉模拟量表（VAS）VAS 严重程度，和眼表面疾病指数（OSDI）问卷。
CyclASol 与载体和 Restasis 相比，在 16 周的治疗期间，角膜和结膜染色均持续减少，起效迅速（第 14 天）。基于混合效应模型的方法表明，CyclASol 药物的效果在统计学上显著优于载体（总角膜染色 P<0.1，中央角膜染色 P<0.001，结膜染色 P<0.01）。基于模型的分析表明，OSDI 作为症状参数具有显著的 CyclASol 作用（P<0.01）。所有治疗组的眼部不良事件数量均较低。
CyclASol 在中重度 DED 中以 2 种浓度显示出疗效、安全性和耐受性。在与开放性标签的 Restasis 的直接头对头比较中，CyclASol 在缓解 DED 的体征方面显示出更早的起效，在治疗 2 周后即可观察到，这一点通过角膜和结膜染色来衡量。对于干眼症患者的视觉功能的重要区域——角膜中央区域，治疗效果最佳。出色的安全性、耐受性和舒适度支持这种新的环孢素制剂具有积极的获益-风险比。
