Oregon Health & Science University, Casey Eye Institute, Portland, Oregon, and VA Portland Health Care System, Portland, Oregon.
Hospital Clinic de Barcelona, Barcelona, Spain.
Ophthalmology. 2018 Jul;125(7):1075-1087. doi: 10.1016/j.ophtha.2017.12.039. Epub 2018 Feb 9.
To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis.
Phase 3, open-label, multicenter clinical trial extension (VISUAL III).
Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF.
Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through 78.
Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff.
Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis; 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis; 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials.
Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified.
评估阿达木单抗在非感染性中间、后部或全葡萄膜炎患者中的安全性和疗效。
第 3 阶段，开放性标签，多中心临床研究扩展（VISUAL III）。
符合治疗失败（TF）标准的成年人，或完成 VISUAL I 或 II（第 3 阶段，随机、双盲、安慰剂对照）且无 TF 的成年人。
患者接受阿达木单抗 40mg，每两周一次。描述了来自 VISUAL III 第 0 周至第 78 周的中期随访数据。
疾病静止、无皮质类固醇激素静止、活动性炎症性脉络膜/视网膜血管病变、前房细胞分级、玻璃体细胞混浊分级、最佳矫正视力（BCVA）和皮质类固醇剂量。二项数据采用无应答者插补（NRI）报告，连续数据采用最后观察值结转和观察到的分析，皮质类固醇剂量采用观察病例分析。从 VISUAL III 中的第一次阿达木单抗剂量开始报告不良事件（AE），直至中期截止。
在纳入的 424 名患者中，371 名患者被纳入意向治疗分析。在研究入组时，371 名患者中有 242 名（65%）患有活动性葡萄膜炎；78 周时，60%（145/242，NRI）达到静止状态，其中 66%（95/143，观察到的）无皮质类固醇激素。在研究入组时，371 名患者中有 129 名（35%）患有非活动性葡萄膜炎；78 周时，74%（96/129，NRI）达到静止状态，其中 93%（89/96，观察到的）无皮质类固醇激素。在活动性葡萄膜炎患者中，炎症病变、前房分级和玻璃体细胞混浊分级最初有所改善，随后下降，而在非活动性葡萄膜炎患者中则保持稳定。在活动性葡萄膜炎患者中，BCVA 从 0 周改善至 78 周（左、右眼均为 0.27 至 0.14 logMAR；观察到的），在非活动性葡萄膜炎患者中保持稳定。在活动性葡萄膜炎患者中，皮质类固醇激素剂量从 13.6mg/天（第 0 周）降至 2.6mg/天（第 78 周），在非活动性葡萄膜炎患者中保持稳定（1.5-1.2mg/天）。AE（424 例事件/100 患者年）和严重 AE（16.5 例事件/100 患者年）与之前的 VISUAL 试验相似。
在研究入组时患有活动性葡萄膜炎的患者接受阿达木单抗治疗后，可能会达到静止状态，提高视力，并减少每日与葡萄膜炎相关的全身皮质类固醇激素的使用。大多数在研究入组时患有非活动性葡萄膜炎的患者保持静止状态，无需增加皮质类固醇激素剂量。未发现新的安全性信号。
