玻璃体内注射阿柏西普治疗雷珠单抗抵抗的新生血管性年龄相关性黄斑变性患者的疗效和安全性。

Efficacy and safety of intravitreal aflibercept in ranibizumab-refractory patients with neovascular age-related macular degeneration.

机构信息

Centre d'Ophtalmologie, 30 Boulevard Heurteloup, 37000, Tours, France.

Centre Hospitalier de la Cr Rousse, Université de Lyon, Lyon, France.

出版信息

BMC Ophthalmol. 2021 Feb 17;21(1):90. doi: 10.1186/s12886-021-01841-6.

DOI:10.1186/s12886-021-01841-6

PMID:33596867

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7890834/

Abstract

BACKGROUND

Anti-vascular endothelial growth factor (anti-VEGF) agents have become the standard of care in neovascular age-related macular degeneration (nAMD). Despite generally excellent response rates to anti-VEGF therapy, some patients do not respond or may respond suboptimally. In the case of refractory or rapidly recurring fluid in nAMD, clinicians may switch to another anti-VEGF agent. TITAN was an observational study that assessed the effectiveness and safety of intravitreal aflibercept (IVT-AFL) in patients with nAMD refractory to ranibizumab who switched to IVT-AFL after less than 12 months of ranibizumab treatment in routine clinical practice in France.

METHODS

TITAN was an observational, retrospective and prospective 12-month study conducted at 28 centres in France. Patients with nAMD refractory to ranibizumab were enrolled. Patients who were switched from ranibizumab to IVT-AFL were followed for 12 months. Data were obtained from medical records for retrospectively included patients, and at routine follow-up visits for those included prospectively. The main outcome measure was percentage of patients who achieved treatment success (gain of ≥1 Early Treatment Diabetic Retinopathy Study letters in best-corrected visual acuity [BCVA] and/or any reduction in central retinal thickness [CRT]) from baseline to 12 months after switching. A sample size of 225 patients was determined based on a 2-sided 95% confidence interval with a width equal to 0.12 when the sample proportion was 0.70.

RESULTS

We analysed safety data (N = 217) and clinical outcomes from patients in the per-protocol population (n = 125). The mean (standard deviation) number of IVT-AFL injections was 7.5 (2.6). Treatment success was achieved in 68.8% of patients. Mean BCVA change from baseline to Month 12 was + 1.5 letters (P = 0.105) and the mean CRT change was - 45.0 μm (P < 0.001). In a subgroup analysis, in patients who received three initial monthly IVT-AFL injections, mean BCVA gain was 3.3 letters at Month 12 (P = 0.015). Excluding lack of efficacy and inappropriate scheduling of drug administration, the most common adverse event was eye pain (2.3%).

CONCLUSIONS

Switching ranibizumab-refractory patients with nAMD to IVT-AFL may improve visual outcomes in some patients, particularly those who receive three initial monthly injections.

TRIAL REGISTRATION

ClinicalTrials.gov , NCT02321241 . First posted: December 22, 2014; Last update posted: July 2, 2018.

摘要

背景

抗血管内皮生长因子（抗-VEGF）药物已成为新生血管性年龄相关性黄斑变性（nAMD）的标准治疗方法。尽管抗-VEGF 治疗的总体反应率通常非常高，但有些患者没有反应，或者反应不佳。在 nAMD 中出现难治性或快速复发的液体时，临床医生可能会改用另一种抗-VEGF 药物。TITAN 是一项观察性研究，评估了在法国常规临床实践中，在接受雷珠单抗治疗不到 12 个月后，对雷珠单抗难治的 nAMD 患者改用玻璃体腔内阿柏西普（IVT-AFL）的有效性和安全性。

方法

TITAN 是一项在法国 28 个中心进行的观察性、回顾性和前瞻性 12 个月研究。招募了对雷珠单抗难治的 nAMD 患者。从雷珠单抗转为 IVT-AFL 的患者接受了 12 个月的随访。回顾性纳入患者的数据来自病历，前瞻性纳入患者的数据来自常规随访。主要观察指标是从基线到改用 IVT-AFL 后 12 个月时治疗成功（最佳矫正视力 [BCVA] 增加≥1 个早期治疗糖尿病视网膜病变研究字母和/或中央视网膜厚度 [CRT] 任何减少）的患者比例。根据双侧 95%置信区间，当样本比例为 0.70 时，宽度等于 0.12，确定了 225 例患者的样本量。

结果

我们分析了安全性数据（N=217）和符合方案人群（n=125）患者的临床结局。IVT-AFL 注射的平均（标准差）次数为 7.5（2.6）。68.8%的患者达到治疗成功。从基线到第 12 个月的平均 BCVA 变化为+1.5 个字母（P=0.105），平均 CRT 变化为-45.0μm（P<0.001）。在亚组分析中，在接受最初三个月每月一次 IVT-AFL 注射的患者中，第 12 个月时平均 BCVA 增益为 3.3 个字母（P=0.015）。除治疗效果不佳和药物管理不当外，最常见的不良事件是眼痛（2.3%）。