Campochiaro Peter A, Eichenbaum David, Chang Margaret A, Clark W Lloyd, Graff Jordan M, Le Pogam Sophie, Cavichini Cordeiro Melina, Gune Shamika, Rabena Mel, Singh Natasha, Lin Stephanie, Callaway Natalia
The Wilmer Eye Institute, Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Retina Vitreous Associates of Florida, St. Petersburg, Florida; Morsani College of Medicine, University of South Florida, Tampa, Florida.
Ophthalmol Retina. 2025 Feb;9(2):144-155. doi: 10.1016/j.oret.2024.05.021. Epub 2024 Aug 30.
The Port Delivery System with ranibizumab (PDS) is approved in the United States for neovascular age-related macular degeneration (nAMD). Portal (NCT03683251) is evaluating long-term safety and tolerability of the PDS in patients with nAMD who completed the phase II Ladder (NCT02510794) or phase III Archway (NCT03677934) trials.
Multicenter, nonrandomized, open-label, extension clinical trial.
All-PDS safety population (N = 555) comprises patients enrolled in Portal who completed Ladder or Archway. Because of data availability, efficacy population comprises Ladder-to-Portal patients only: patients who previously received PDS 10, 40, or 100 mg/mL pro re nata (as-needed [PRN]; n = 58, 62, and 59, respectively) or monthly intravitreal ranibizumab 0.5-mg injections (monthly ranibizumab; n = 41) in Ladder and subsequently enrolled in Portal.
Ladder patients received PDS refill-exchanges PRN or monthly ranibizumab. Archway patients received PDS 100 mg/mL with fixed refill-exchanges every 24 weeks (Q24W) or monthly ranibizumab. Once enrolled in Portal, all patients receive PDS Q24W from day 1.
Ocular adverse events of special interest (AESIs); changes from baseline in best-corrected visual acuity (BCVA) and center point thickness (CPT); supplemental ranibizumab treatment between refill-exchange procedures; and PDS Patient Preference Questionnaire results.
In the All-PDS safety population (mean follow-up, 111 weeks), 137 (24.7%) patients had ≥1 ocular AESI; most common were cataract (11.4%), vitreous hemorrhage (6.1%), and conjunctival thickening (bleb)/filtering bleb leak (6.3%). Endophthalmitis occurred in 11 of 555 (2.0%) patients. For Ladder-to-Portal patients previously treated with PDS 100 mg/mL or monthly ranibizumab, BCVA remained stable from baseline to month 48; mean (95% confidence interval) changes from baseline were 0.1 (-6.6 to 6.8; n = 31) and 2.3 (-9.4 to 14.1; n = 15) letters, respectively; CPT remained stable through month 48. Approximately 95% of patients did not need supplemental treatment before each refill-exchange for >2 years since Portal enrollment. Of Ladder-to-Portal previous monthly ranibizumab patients, 92% preferred the PDS over injections.
Interim results from Portal suggest 4-year maintenance of visual/anatomic outcomes with PDS 100 mg/mL, with the PDS preferred to monthly injections. Long-term safety profile of the PDS is well characterized.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
雷珠单抗眼内植入系统（PDS）在美国已被批准用于治疗新生血管性年龄相关性黄斑变性（nAMD）。PORTAL研究（NCT03683251）正在评估PDS在完成II期阶梯研究（NCT02510794）或III期拱廊研究（NCT03677934）的nAMD患者中的长期安全性和耐受性。
多中心、非随机、开放标签的扩展临床试验。
所有PDS安全性人群（N = 555）包括PORTAL研究中完成阶梯研究或拱廊研究的患者。由于数据可用性，疗效人群仅包括从阶梯研究转入PORTAL研究的患者：这些患者在阶梯研究中之前按需接受过10、40或100mg/mL的PDS（分别为n = 58、62和59）或每月一次玻璃体内注射0.5mg雷珠单抗（每月雷珠单抗组；n = 41），随后参加了PORTAL研究。
阶梯研究的患者按需或每月接受雷珠单抗进行PDS再填充交换。拱廊研究的患者接受100mg/mL的PDS，每24周进行一次固定的再填充交换（Q24W）或每月接受雷珠单抗。一旦进入PORTAL研究，所有患者从第1天起每24周接受一次PDS。
特别关注的眼部不良事件（AESIs）；最佳矫正视力（BCVA）和中心点厚度（CPT）相对于基线的变化；再填充交换程序之间的补充雷珠单抗治疗；以及PDS患者偏好问卷结果。
在所有PDS安全性人群中（平均随访111周），137名（24.7%）患者发生了≥1次眼部AESIs；最常见的是白内障（11.4%）、玻璃体积血（6.1%）和结膜增厚（水泡）/滤过泡渗漏（6.3%）。555名患者中有11名（2.0%）发生了眼内炎。对于之前接受过100mg/mL PDS或每月雷珠单抗治疗的从阶梯研究转入PORTAL研究的患者，BCVA从基线到48个月保持稳定；相对于基线的平均（95%置信区间）变化分别为0.1（-6.6至6.8；n = 31）和2.3（-9.4至14.1；n = 15）个字母；CPT在48个月内保持稳定。自进入PORTAL研究以来，约95%的患者在每次再填充交换前超过2年不需要补充治疗。在之前接受每月雷珠单抗治疗的从阶梯研究转入PORTAL研究的患者中，92%的患者更喜欢PDS而不是注射治疗。
PORTAL研究的中期结果表明，100mg/mL的PDS可维持4年的视力/解剖学结果，且患者更喜欢PDS而非每月注射治疗。PDS的长期安全性特征已得到充分描述。
在本文末尾的脚注和披露中可能会发现专有或商业披露信息。
