Wills Eye Hospital, Thomas Jefferson University, Mid Atlantic Retina, Philadelphia, Pennsylvania.
Austin Clinical Research, Austin, Texas.
Ophthalmology. 2023 Jul;130(7):735-747. doi: 10.1016/j.ophtha.2023.02.024. Epub 2023 Mar 2.
To report 2-year results from the Archway clinical trial of the Port Delivery System with ranibizumab (PDS) for treatment of neovascular age-related macular degeneration (nAMD).
Phase 3, randomized, multicenter, open-label, active-comparator-controlled trial.
Patients with previously treated nAMD diagnosed within 9 months of screening and responsive to anti-vascular endothelial growth factor therapy.
Patients were randomized 3:2 to PDS with ranibizumab 100 mg/ml with fixed refill-exchanges every 24 weeks (PDS Q24W) or intravitreal ranibizumab 0.5 mg injections every 4 weeks (monthly ranibizumab). Patients were followed through 4 complete refill-exchange intervals (∼2 years).
Change in best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score from baseline averaged over weeks 44 and 48, weeks 60 and 64, and weeks 88 and 92 (noninferiority margin, -3.9 ETDRS letters).
The PDS Q24W was noninferior to monthly ranibizumab, with differences in adjusted mean change in BCVA score from baseline averaged over weeks 44/48, 60/64 and 88/92 of -0.2 (95% confidence interval [CI], -1.8 to +1.3), +0.4 (95% CI, -1.4 to +2.1) and -0.6 ETDRS letters (95% CI, -2.5 to +1.3), respectively. Anatomic outcomes were generally comparable between arms through week 96. Through each of 4 PDS refill-exchange intervals, 98.4%, 94.6%, 94.8%, and 94.7% of PDS Q24W patients assessed did not receive supplemental ranibizumab treatment. The PDS ocular safety profile was generally unchanged from primary analysis. Prespecified ocular adverse events of special interest (AESI) were reported in 59 (23.8%) PDS and 17 (10.2%) monthly ranibizumab patients. The most common AESI reported in both arms was cataract (PDS Q24W, 22 [8.9%]; monthly ranibizumab, 10 [6.0%]). Events in the PDS Q24W arm included (patient incidence) 10 (4.0%) conjunctival erosions, 6 (2.4%) conjunctival retractions, 4 (1.6%) endophthalmitis cases, and 4 (1.6%) implant dislocations. Serum ranibizumab sampling showed that the PDS continuously released ranibizumab over the 24-week refill-exchange interval and ranibizumab serum concentrations were within the range experienced with monthly ranibizumab.
The PDS Q24W showed noninferior efficacy to monthly ranibizumab through approximately 2 years, with approximately 95% of PDS Q24W patients not receiving supplemental ranibizumab treatment in each refill-exchange interval. The AESIs were generally manageable, with learnings continually implemented to minimize PDS-related AEs.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
报告使用载药系统（PDS）与雷珠单抗治疗新生血管性年龄相关性黄斑变性（nAMD）的 Archway 临床试验的 2 年结果。
3 期、随机、多中心、开放标签、阳性对照对照临床试验。
在筛选后 9 个月内诊断出先前治疗过的 nAMD 且对血管内皮生长因子治疗有反应的患者。
患者随机分为 3:2 接受 PDS 与 100mg/ml 雷珠单抗，每 24 周固定进行一次补充交换（PDS Q24W）或每 4 周进行一次玻璃体内雷珠单抗 0.5mg 注射（每月雷珠单抗）。患者在 4 个完整的补充交换间隔内（约 2 年）接受随访。
从基线到第 44 周和第 48 周、第 60 周和第 64 周以及第 88 周和第 92 周的最佳矫正视力（BCVA）早期治疗糖尿病视网膜病变研究（ETDRS）字母评分的平均变化（非劣效性边界为-3.9 ETDRS 字母）。
PDS Q24W 不劣于每月雷珠单抗，从基线到第 44/48、60/64 和 88/92 周的平均 BCVA 评分调整后差异为-0.2（95%置信区间 [CI]，-1.8 至 1.3）、+0.4（95% CI，-1.4 至 2.1）和-0.6 ETDRS 字母（95% CI，-2.5 至 1.3）。在第 96 周，两个手臂的解剖学结果基本相似。在每个 PDS 补充交换间隔内，98.4%、94.6%、94.8%和 94.7%接受评估的 PDS Q24W 患者未接受补充雷珠单抗治疗。PDS 的眼部安全性概况与主要分析基本保持不变。在规定的眼部不良事件特别关注（AESI）中，59 例（23.8%）PDS 和 17 例（10.2%）每月雷珠单抗患者出现了这些情况。在两个手臂中报告的最常见 AESI 是白内障（PDS Q24W，22 [8.9%]；每月雷珠单抗，10 [6.0%]）。PDS Q24W 手臂中的事件包括（患者发病率）10 例（4.0%）结膜糜烂、6 例（2.4%）结膜收缩、4 例（1.6%）眼内炎病例和 4 例（1.6%）植入物脱位。雷珠单抗的血清样本显示，PDS 在 24 周的补充交换间隔内持续释放雷珠单抗，雷珠单抗的血清浓度在每月接受雷珠单抗治疗的范围内。
在大约 2 年的时间内，PDS Q24W 显示出不劣于每月雷珠单抗的疗效，在每个补充交换间隔内，约 95%的 PDS Q24W 患者未接受补充雷珠单抗治疗。AESI 通常是可控的，不断学习以尽量减少与 PDS 相关的 AE。
可能在参考文献之后找到专有或商业披露信息。
