Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.
Texas Retina Associates, Arlington, Texas.
Ophthalmology. 2019 Mar;126(3):428-437. doi: 10.1016/j.ophtha.2018.09.044. Epub 2018 Oct 11.
To assess efficacy and safety of sarilumab, a human anti-interleukin-6 receptor antibody, for treatment of posterior segment noninfectious uveitis (NIU).
Randomized, double-masked, placebo-controlled, phase 2 study.
Fifty-eight patients (eyes) with noninfectious intermediate, posterior, or panuveitis.
Eyes received treatment every 2 weeks for 16 weeks with subcutaneous sarilumab 200 mg or placebo.
The primary end point was the proportion of patients with ≥2-step reduction in vitreous haze (VH) on the Miami scale or with a reduction of systemic corticosteroids (prednisolone or equivalent) to a dose of <10 mg/day at week 16. Primary end point was based on VH evaluation by a central reading center. Investigator evaluation of VH was a prespecified, planned secondary analysis.
At week 16, proportion of patients taking sarilumab or placebo with ≥2-step reduction in VH or corticosteroid dose <10 mg/day was 46.1% vs. 30.0% (P = 0.2354) based on central reading center assessment of VH and 64.0% vs. 35.0% (P = 0.0372) based on investigator assessment of VH, respectively. In the subgroup of eyes with VH grade ≥2 at baseline, the mean VH reduction from baseline to week 16 was significantly greater with sarilumab vs. placebo regardless of assessment by the central reading center (-2.1 [n = 11] vs. -1.7 [n = 3], respectively; P = 0.0255) or investigator (-2.5 [n = 19] vs. -1.2 [n = 11], respectively; P = 0.0170). The mean best-corrected visual acuity gain from baseline to week 16 was greater with sarilumab vs. placebo in the overall population (8.9 vs. 3.6 letters, respectively; P = 0.0333) and in the subgroup of eyes with central subfield thickness (CST) ≥300 μm at baseline (12.2 [n = 13] vs. 2.1 [n = 7] letters, respectively; P = 0.0517). Corresponding changes in CST were -46.8 vs. +2.6 μm (P = 0.0683) in the overall population and -112.5 [n = 13] vs. -1.8 [n = 6] μm (P = 0.1317) in the subgroup of eyes with CST ≥300 μm at baseline, respectively. The most common ocular adverse events were worsening of uveitis (0 [placebo] and 3 [sarilumab] patients) and retinal infiltrates (1 [placebo] and 2 [sarilumab] patients).
Subcutaneous sarilumab may provide clinical benefits in the management of NIU of the posterior segment, especially in eyes with uveitic macular edema.
评估人源抗白细胞介素-6 受体单克隆抗体 sarilumab 治疗后节段非感染性葡萄膜炎（NIU）的疗效和安全性。
随机、双盲、安慰剂对照、2 期研究。
58 例（眼）患有中间、后段或全葡萄膜炎的非感染性患者。
每 2 周接受一次皮下 sarilumab 200mg 或安慰剂治疗，共 16 周。
主要终点是接受 Miami 量表评估的玻璃体混浊（VH）改善≥2 级或全身皮质类固醇（泼尼松龙或等效物）剂量减少至每周<10mg 的患者比例在第 16 周。主要终点基于中央阅读中心对 VH 的评估。对 VH 的研究者评估是预先指定的、计划中的次要分析。
在第 16 周，接受 sarilumab 或安慰剂治疗的患者中，VH 改善≥2 级或皮质类固醇剂量<10mg/天的比例分别为 46.1%和 30.0%（P=0.2354），基于中央阅读中心评估的 VH；分别为 64.0%和 35.0%（P=0.0372），基于研究者评估的 VH。在基线 VH 分级≥2 的亚组中，与安慰剂相比，sarilumab 治疗后 16 周的 VH 平均下降幅度显著更大，无论由中央阅读中心（-2.1[n=11]vs.-1.7[n=3]，P=0.0255）还是研究者（-2.5[n=19]vs.-1.2[n=11]，P=0.0170）评估。在总体人群中（8.9 对 3.6 个字母，P=0.0333）和基线中央区视网膜厚度（CST）≥300μm 的亚组中（12.2[n=13]对 2.1[n=7]个字母，P=0.0517），与安慰剂相比，接受 sarilumab 治疗的患者最佳矫正视力从基线到第 16 周的平均增益更大。在总体人群中，相应的 CST 变化为-46.8μm 对+2.6μm（P=0.0683），在基线 CST≥300μm 的亚组中，相应的 CST 变化为-112.5μm 对-1.8μm（P=0.1317）。最常见的眼部不良事件是葡萄膜炎恶化（0[安慰剂]和 3[sarilumab]患者）和视网膜浸润（1[安慰剂]和 2[sarilumab]患者）。
皮下注射 sarilumab 可能为后节段 NIU 的治疗提供临床获益，特别是在患有葡萄膜炎性黄斑水肿的眼中。
