Regillo Carl, Kaiser Peter K, Kertes Peter J, Gillies Mark, Maio-Twofoot Tina, D'Souza Divya, Guenther Siegbert, Lawrence David, Holz Frank G
Retina Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania.
Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.
Ophthalmol Retina. 2025 Jun 2. doi: 10.1016/j.oret.2025.05.030.
To compare the efficacy and safety of brolucizumab 6 mg and aflibercept 2 mg using an identical 4-week adjustment treat-and-extend regimen in patients with neovascular age-related macular degeneration (nAMD).
Randomized, double-masked, multicenter, active-controlled, 2-arm, phase IIIb study.
Patients (N = 737) with untreated, active choroidal neovascularization secondary to nAMD.
Patients were randomized 1:1 to either brolucizumab 6 mg or aflibercept 2 mg with injections at weeks 0, 4, 8, and 16 followed by 4-week interval adjustments depending on disease activity (DA) up to intervals of 16 weeks. After the introduction of the urgent safety measure, patients requiring a 4-week interval were discontinued from study treatment and moved to the standard of care.
Coprimary end points were the distribution of the last treatment interval with no DA at week 32 and the average change in best-corrected visual acuity (BCVA) from baseline to weeks 28 and 32. Key secondary end points included average change from baseline in central subfield thickness (CSFT), presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF), and subretinal pigment epithelium fluid at weeks 28 and 32. Safety end points included the incidence of ocular and nonocular adverse events (AEs) and AEs of special interest (AESIs).
Brolucizumab achieved superiority to aflibercept in the distribution of last interval with no DA at week 32 (proportion of patients on 12-week treatment intervals: 38.5% vs. 19.8%; 8 weeks: 35.8% vs. 39.9%; 4 weeks: 25.7% vs. 40.2%, respectively; P < 0.0001) and noninferiority to aflibercept for least square mean difference in average change in BCVA from baseline at weeks 28 and 32 (+5.2 vs. +5.1; P < 0.0001). The least square mean difference in the average change in CSFT (μm) from baseline at weeks 28 and 32 (brolucizumab -172.8 vs. aflibercept -142.5) was -30.3 (P = 0.002). Fewer brolucizumab versus aflibercept patients had IRF and/or SRF and subretinal pigment epithelium fluid. Incidences of ocular AEs, serious ocular AEs, and AESIs in the brolucizumab versus aflibercept arms were 29.2% versus 26.1%, 2.5% versus 0.5%, and 5.5% versus 1.1%, respectively.
In TALON, more brolucizumab-treated patients achieved longer treatment intervals without DA than aflibercept with comparable visual gains. Brolucizumab showed improved anatomical outcomes and demonstrated an overall favorable benefit/risk profile.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
在新生血管性年龄相关性黄斑变性（nAMD）患者中，使用相同的4周调整治疗与延长方案比较6mg布罗鲁单抗和2mg阿柏西普的疗效和安全性。
随机、双盲、多中心、活性药物对照、双臂IIIb期研究。
未经治疗的、继发于nAMD的活动性脉络膜新生血管患者（N = 737）。
患者按1:1随机分组，分别接受6mg布罗鲁单抗或2mg阿柏西普治疗，在第0、4、8和16周注射，随后根据疾病活动度（DA）进行4周间隔调整，最长间隔为16周。引入紧急安全措施后，需要4周间隔的患者停止研究治疗并转为接受标准治疗。
共同主要终点为第32周无DA的最后治疗间隔分布，以及从基线到第28周和32周最佳矫正视力（BCVA）的平均变化。关键次要终点包括第28周和32周时中心子场厚度（CSFT）相对于基线的平均变化、视网膜内液（IRF）和/或视网膜下液（SRF）的存在情况，以及视网膜色素上皮下液。安全终点包括眼部和非眼部不良事件（AE）的发生率以及特别关注的不良事件（AESI）。
在第32周无DA的最后间隔分布方面，布罗鲁单抗优于阿柏西普（接受12周治疗间隔的患者比例：分别为38.5%对19.8%；8周：35.8%对39.9%；4周：25.7%对40.2%；P < 0.0001），并且在第28周和32周时，BCVA从基线的平均变化的最小二乘均差方面不劣于阿柏西普（+5.2对+5.1；P < 0.0001）。第28周和32周时CSFT相对于基线的平均变化（μm）的最小二乘均差（布罗鲁单抗 -172.8对阿柏西普 -142.5）为-30.3（P = 0.002）。与阿柏西普相比，接受布罗鲁单抗治疗的患者出现IRF和/或SRF以及视网膜色素上皮下液的情况较少。布罗鲁单抗组与阿柏西普组的眼部AE、严重眼部AE和AESI的发生率分别为29.2%对26.1%、2.5%对0.5%和5.5%对1.1%。
在TALON研究中，与阿柏西普相比，更多接受布罗鲁单抗治疗的患者在无DA的情况下实现了更长的治疗间隔，且视力改善相当。布罗鲁单抗显示出更好的解剖学结果，并具有总体良好的获益/风险特征。
专有或商业披露信息可在本文末尾的脚注和披露内容中找到。
