Institut Clínic d'Oftalmologia, Hospital Clínic de Barcelona, Barcelona, Spain.
Universitat de Barcelona, Barcelona, Spain.
Retina. 2018 Jul;38(7):1361-1370. doi: 10.1097/IAE.0000000000001690.
To report the 24-month efficacy and safety of the interleukin-6 receptor antagonist tocilizumab (TCZ) for refractory uveitis-related macular edema (ME).
Data were obtained by standardized chart review. Patients with quiescent uveitis seen at a single tertiary referral center, for whom ME was the principal cause of reduced visual acuity.
Central foveal thickness measured by optical coherence tomography; degree of anterior and posterior chamber; inflammation (Standardization of Uveitis Nomenclature Working Group criteria); and visual acuity (Snellen and logarithm of the minimum angle of resolution) were recorded in all patients during TCZ therapy at months 1, 3, 6, 12, 18, and 24.
Sixteen eyes from 12 patients (10 women) were included. Mean age was 34.6 years. Mean duration of ME was 13.2 years. All patients achieved 24 months of follow-up and that is the census date for data collection. Before TCZ was commenced, ME was present, and all patients had been previously treated with immunosuppressive therapy and biologic agents. Uveitis diagnoses were juvenile idiopathic arthritis associated, uveitis (n = 6), birdshot chorioretinopathy (n = 2), idiopathic panuveitis (n = 2), sympathetic ophthalmia (n = 1), and ankylosing spondylitis (n = 1). Mean central foveal thickness (95%; confidence interval) was 516 ± 55 μm at baseline, improving to 274 ± 13 at Month 12 (P = 0.0004), and sustained at 274 ± 14 at Month 24 of follow-up (P = 0.00039). Mean logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.78 ± 0.18 (Snellen 20/120 ± 20/30) at baseline to 0.42 ± 0.17 (20/52 ± 20/30) at Month 12 (P = 0.0001) and 0.40 ± 0.17 (20/50 ± 20/30) at Month 24 of follow-up (P = 0.0002). Tocilizumab therapy was withdrawn in 5 patients with sustained remission at Month 12 but in all, ME relapsed between 1 and 3 months after TCZ discontinuation. Rechallenge of TCZ infusions led to recovery of uveitis control and ME resolution. Two adverse events were reported during two 4-month follow-ups: one Grade 1 neutropenia and one community-acquired pneumonia.
In this long-term study, TCZ was effective and had a comparable safety profile to published data for TCZ use in other indications, when used for the treatment of refractory uveitis-related ME.
报告白细胞介素-6 受体拮抗剂托珠单抗(TCZ)治疗难治性葡萄膜炎相关黄斑水肿(ME)的 24 个月疗效和安全性。
通过标准化图表回顾获取数据。在一家三级转诊中心就诊的处于静止期葡萄膜炎患者,ME 是其视力下降的主要原因。
所有患者在 TCZ 治疗的第 1、3、6、12、18 和 24 个月时,通过光学相干断层扫描测量中央视网膜厚度;前房和后房的程度;炎症(葡萄膜炎命名标准化工作组标准);视力(Snellen 和最小角度分辨率的对数)。
12 名患者(10 名女性)的 16 只眼被纳入研究。平均年龄为 34.6 岁。ME 的平均持续时间为 13.2 年。所有患者均完成了 24 个月的随访,这也是数据收集的截止日期。在开始使用 TCZ 之前,ME 已经存在,所有患者之前都接受过免疫抑制治疗和生物制剂治疗。葡萄膜炎的诊断包括幼年特发性关节炎相关葡萄膜炎(n = 6)、鸟枪弹样脉络膜视网膜病变(n = 2)、特发性全葡萄膜炎(n = 2)、交感神经眼炎(n = 1)和强直性脊柱炎(n = 1)。基线时的平均中央视网膜厚度(95%置信区间)为 516 ± 55μm,在第 12 个月时改善至 274 ± 13μm(P = 0.0004),并在第 24 个月的随访中维持在 274 ± 14μm(P = 0.00039)。最佳矫正视力对数最小角度分辨率从基线时的 0.78 ± 0.18(Snellen 20/120 ± 20/30)提高到第 12 个月时的 0.42 ± 0.17(20/52 ± 20/30)(P = 0.0001)和第 24 个月时的 0.40 ± 0.17(20/50 ± 20/30)(P = 0.0002)。在第 12 个月时持续缓解的 5 名患者中停用 TCZ,但所有患者在 TCZ 停药后 1 至 3 个月内 ME 均复发。重新使用 TCZ 输注可恢复葡萄膜炎控制和 ME 消退。在两次为期 4 个月的随访中报告了 2 起不良事件:1 例 1 级中性粒细胞减少症和 1 例社区获得性肺炎。
在这项长期研究中,TCZ 治疗难治性葡萄膜炎相关 ME 的疗效与已发表的 TCZ 用于其他适应证的数据相当,安全性也可接受。