Purpose

To evaluate the efficacy and safety of intravitreal sirolimus in the management of noninfectious uveitis of the posterior segment (NIU-PS).

Design

Combined analysis of 2 phase 3, randomized, double-masked, multinational, 6-month studies.

Participants

Adults with active NIU-PS (intermediate uveitis, posterior uveitis, or panuveitis; defined as vitreous haze [VH] ≥1.5+ on modified Standardization of Uveitis Nomenclature scale).

Methods

Patients were randomized 1:1:1 to receive intravitreal sirolimus 44 μg (n = 208), 440 μg (n = 208), or 880 μg (n = 177) on days 1, 60, and 120. Patients discontinued medications for NIU-PS except for systemic corticosteroids, which were tapered according to protocol. Enrollment in the 880-μg group was terminated after interim results found no significant difference in efficacy compared with the 440-μg dose.

Main Outcome Measures

The primary efficacy end point was the percentage of patients with VH of 0 at month 5 in the study eye without the use of rescue therapy. Secondary efficacy end points included VH of 0 or 0.5+, corticosteroid-tapering success, and changes in best-corrected visual acuity (BCVA). Safety measures included ocular and nonocular adverse events.

Results

A total of 592 patients were randomized. Significantly higher proportions of patients treated with 440 μg compared with 44 μg intravitreal sirolimus achieved VH of 0 (21.2% vs. 13.5%; P = 0.038) and VH of 0 or 0.5+ (50.0% vs. 40.4%; P = 0.049) at month 5. Best-corrected visual acuity was stable (absolute change <5 ETDRS letters) or improved >5 letters in 80.1% and 80.2% of patients in the 440-μg and 44-μg groups, respectively. At month 5, corticosteroids were tapered successfully in 69.6% and 68.8% of patients in the 440-μg and 44-μg groups, and among these patients, VH of 0 or 0.5+ was achieved by 43.5% and 28.1% in the 440-μg and 44-μg groups. Both doses were generally well tolerated. Mean changes from baseline intraocular pressure (IOP) in the study eye at each analysis visit were minimal in all treatment groups.

Conclusions

Intravitreal sirolimus 440 μg improved ocular inflammation, as measured by VH, compared with the 44-μg dose, with minimal impact on IOP, while preserving BCVA.

中文翻译：

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玻璃体玻璃体西罗莫司对后段非感染性葡萄膜炎的疗效和安全性：西罗莫司研究评估双层葡萄膜炎治疗（SAKURA）计划的结果。

目的

评估玻璃体内西罗莫司治疗后段非感染性葡萄膜炎（NIU-PS）的有效性和安全性。

设计

对2个3期，随机，双掩盖，跨国，6个月研究的合并分析。

参加者

患有活动性NIU-PS（中性葡萄膜炎，后葡萄膜炎或胰腺炎；根据改良的葡萄膜炎命名法标准定义为玻璃体雾度[VH]≥1.5+）的成年人。

方法

患者在第1、60和120天以1：1的比例随机接受玻璃体内西罗莫司44μg（n = 208），440μg（n = 208）或880μg（n = 177）。患者停止使用NIU药物-PS，除​​全身性皮质类固醇激素外，后者根据治疗方案逐渐缩小。中期结果发现与440μg剂量相比疗效无显着差异后，终止880μg组的入组。

主要观察指标

主要疗效终点是研究眼中在不使用急救疗法的情况下，第5个月VH为0的患者所占的百分比。次要疗效终点包括VH为0或0.5+，糖皮质激素治疗成功和最佳矫正视力（BCVA）的变化。安全措施包括眼部和非眼部不良事件。

结果

共有592例患者被随机分组​​。与 440μg玻璃体内西罗莫司相比，接受440μg治疗的患者的VH为0（21.2％比13.5％; P = 0.038），VH为0或0.5+（50.0％比40.4％; P 在第5个月时= 0.049）。最佳校正后的视力稳定（绝对变化<5 ETDRS字母）或440μg和44μg组分别有80.1％和80.2％的患者改善了> 5字母。在第5个月，在440-μg和44-μg组中，糖皮质激素成功地逐渐减少了69.6％和68.8％的患者，在这些患者中，440-g和440-g中的VH为0或0.5+微克和44微克组。两种剂量通常耐受良好。在所有治疗组中，每次分析访视时研究眼的基线眼内压（IOP）的平均变化均很小。

结论

通过VH测量，与44μg剂量相比，玻璃体内西罗莫司440μg改善了眼部炎症，对IOP的影响最小，同时保留了BCVA。