Acucela Inc., 818 Stewart St., Suite 1110, Seattle, WA, 98101-1479, USA.
Retina Consultants of Austin, 3705 Medical Parkway, Suite 410, Austin, TX, 78705, USA.
Graefes Arch Clin Exp Ophthalmol. 2021 Feb;259(2):369-378. doi: 10.1007/s00417-020-04899-y. Epub 2020 Aug 27.
To evaluate the effects of oral emixustat hydrochloride on pro-angiogenic and inflammatory cytokines in the aqueous humor, as well as other ophthalmic parameters, in subjects with proliferative diabetic retinopathy (PDR).
Twenty-three patients with PDR, with or without diabetic macular edema (DME), were assigned to emixustat or placebo in daily oral doses ranging from 5 to 40 mg over a step-up titration period, for 84 days. The main outcome measures included levels of IL-1β, IL-6, IL-8, TGFβ-1, and VEGF in the aqueous humor.
Seven of 12 subjects (58%) who were randomized to emixustat and 11 of 12 subjects (92%) who were randomized to placebo completed the study. No statistically significant differences between treatment groups were observed for changes in any of the aqueous humor cytokines tested. However, median VEGF levels were slightly reduced in the emixustat but not the placebo group (- 70.0 pg/mL versus + 42.7 pg/mL, or - 11.8% versus + 6.7%). In a post hoc analysis of all subjects (with or without DME), statistically significant differences between treatment arms in mean changes from baseline in central subfield thickness (CST; emixustat - 11.9 μm, placebo + 36.2 μm; P = 0.076) and total macular volume (TMV; emixustat - 0.13 mm, placebo + 0.23 mm; P = 0.026) were observed, both favoring emixustat. Emixustat's safety profile was consistent with prior studies (i.e., the adverse events of delayed dark adaptation and visual impairment were more common in subjects treated with emixustat).
Although this pilot study did not demonstrate statistically significant differences in changes in aqueous humor cytokine levels between the emixustat and placebo groups, VEGF levels were slightly reduced in the emixustat but not in the placebo group. In addition, statistically significant differences favoring the emixustat group were observed in CST and TMV among all subjects. These data warrant further investigation of emixustat's potential therapeutic effects in diabetic retinopathy.
ClinicalTrials.gov identifier: NCT02753400 (April 2016).
评估盐酸依美斯汀口服给药对增生型糖尿病视网膜病变（PDR）患者房水中促血管生成和炎症细胞因子以及其他眼部参数的影响。
23 例 PDR 患者（伴或不伴糖尿病黄斑水肿 [DME]）接受每日口服 emixustat 或安慰剂治疗，剂量范围为 5-40mg，滴定期为 84 天。主要观察指标包括房水中白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、转化生长因子-β1（TGFβ-1）和血管内皮生长因子（VEGF）的水平。
随机分配至 emixustat 组的 12 例患者中有 7 例（58%）和随机分配至安慰剂组的 12 例患者中有 11 例（92%）完成了研究。两组间任何检测到的房水细胞因子的变化均无统计学差异。然而，emixustat 组的 VEGF 水平略有降低（-70.0pg/ml 比+42.7pg/ml，或-11.8%比+6.7%），而安慰剂组的 VEGF 水平则略有升高。在所有受试者（伴或不伴 DME）的事后分析中，发现治疗组间中央视网膜神经纤维层厚度（CST；emixustat-11.9μm，安慰剂+36.2μm；P=0.076）和全视网膜容积（TMV；emixustat-0.13mm，安慰剂+0.23mm；P=0.026）的平均变化存在统计学差异，均有利于 emixustat。emixustat 的安全性特征与既往研究一致（即，接受 emixustat 治疗的患者更常出现暗适应延迟和视力损害等不良反应）。
尽管本初步研究未显示 emixustat 组和安慰剂组间房水细胞因子水平变化存在统计学差异，但 emixustat 组的 VEGF 水平略有降低，而安慰剂组的 VEGF 水平则略有升高。此外，所有受试者中 CST 和 TMV 的变化均以 emixustat 组更为有利，存在统计学差异。这些数据提示需要进一步研究 emixustat 治疗糖尿病视网膜病变的潜在疗效。
ClinicalTrials.gov 标识符：NCT02753400（2016 年 4 月）。
