■尽管在地理萎缩(GA)的详细成像方面具有广泛的可用性和共识,光谱域光学相干断层扫描(SD-OCT)可能受益于GA诊断中的自动定量OCT分析,监测,并报告其具有里程碑意义的临床试验。
■分析pegcetacoplan与一致GASD-OCT终点之间的关联。
■这是对来自2项平行3期研究的1258名参与者中的936名的11614个SD-OCT卷的事后分析,比较玻璃体腔内APL-2治疗与假注射治疗继发于年龄相关性黄斑变性(OAKS)的地理萎缩(GA)患者的疗效和安全性的研究,以及比较玻璃体腔内APL-2治疗的疗效和安全性的研究。OAKS和DERBY是24个月,多中心,随机化,双面蒙面,2018年8月至2020年7月,在眼底自发荧光成像上对总面积为2.5至17.5mm2的GA成人进行了假对照研究(如果多焦点,至少1个病灶≥1.25mm2)。这项分析是在2023年9月至12月进行的。
■研究参与者接受了pegcetacoplan,每0.1毫升玻璃体内注射15毫克,每月或每隔一个月,或假注射每月或每隔一个月。
■主要终点是3个治疗组中每个治疗组中的视网膜色素上皮面积和外部视网膜萎缩相对于基线的最小二乘均值变化(pegcetacoplan每月,pegcetacoplan每隔一个月,并在24个月时合并假[每月假和每隔一个月假])。通过早期治疗糖尿病视网膜病变研究(ETDRS)感兴趣区域(即,中央凹,侧腹,和中心凹)。
■在936名参与者中,平均(SD)年龄为78.5(7.22)岁,570名参与者(60.9%)为女性。Pegcetacoplan,但不是假治疗,在长达24个月的时间内,与GA的SD-OCT生物标志物的生长速率降低相关。在3至24个月的每个时间点均可检测到视网膜色素上皮和外部视网膜萎缩面积相对于基线的最小二乘均值(SE)变化(最小二乘均值与合并的假手术在24个月,pegcetacoplan每月:-0.86mm2;95%CI,-1.15至-0.57;P<.001;pegcetacoplan每隔一个月:-0.69;95%CI-39,P<这种关联在更频繁的给药(pegcetacoplan每月与pegcetacoplan每隔一个月在第24个月:-0.17mm2;95%CI,-0.43至0.08;P=.17)。在每月的pegcetacoplan和每隔一个月的pegcetacoplan中,在半凹和中央凹区域都观察到了更强的关联。
■这些发现为pegcetacoplan对GA发展的潜在影响提供了更多的见解,包括对视网膜色素上皮和光感受器的潜在影响。
■ClinicalTrials.gov标识符:NCT03525600和NCT03525613。
UNASSIGNED: Despite widespread availability and
consensus on its advantages for detailed imaging of geographic atrophy (GA), spectral-domain optical coherence tomography (SD-OCT) might benefit from automated quantitative OCT analyses in GA diagnosis, monitoring, and reporting of its landmark clinical trials.
UNASSIGNED: To analyze the association between pegcetacoplan and
consensus GA SD-OCT end points.
UNASSIGNED: This was a post hoc analysis of 11 614 SD-OCT volumes from 936 of the 1258 participants in 2 parallel phase 3 studies, the Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (OAKS) and Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (DERBY). OAKS and DERBY were 24-month, multicenter, randomized, double-masked, sham-controlled studies conducted from August 2018 to July 2020 among adults with GA with total area 2.5 to 17.5 mm2 on fundus autofluorescence imaging (if multifocal, at least 1 lesion ≥1.25 mm2). This analysis was conducted from September to December 2023.
UNASSIGNED: Study participants received pegcetacoplan, 15 mg per 0.1-mL intravitreal injection, monthly or every other month, or sham injection monthly or every other month.
UNASSIGNED: The primary end point was the least squares mean change from baseline in area of retinal pigment epithelium and outer
retinal atrophy in each of the 3 treatment arms (pegcetacoplan monthly, pegcetacoplan every other month, and pooled sham [sham monthly and sham every other month]) at 24 months. Feature-specific area analysis was conducted by Early Treatment Diabetic Retinopathy Study (ETDRS) regions of interest (ie, foveal, parafoveal, and perifoveal).
UNASSIGNED: Among 936 participants, the mean (SD) age was 78.5 (7.22) years, and 570 participants (60.9%) were female. Pegcetacoplan, but not sham treatment, was associated with reduced growth rates of SD-OCT biomarkers for GA for up to 24 months. Reductions vs sham in least squares mean (SE) change from baseline of
retinal pigment epithelium and outer
retinal atrophy area were detectable at every time point from 3 through 24 months (least squares mean difference vs pooled sham at month 24, pegcetacoplan monthly: -0.86 mm2; 95% CI, -1.15 to -0.57; P < .001; pegcetacoplan every other month: -0.69 mm2; 95% CI, -0.98 to -0.39; P < .001). This association was more pronounced with more frequent dosing (pegcetacoplan monthly vs pegcetacoplan every other month at month 24: -0.17 mm2; 95% CI, -0.43 to 0.08; P = .17). Stronger associations were observed in the parafoveal and perifoveal regions for both pegcetacoplan monthly and pegcetacoplan every other month.
UNASSIGNED: These findings offer additional insight into the potential effects of pegcetacoplan on the development of GA, including potential effects on the retinal pigment epithelium and photoreceptors.
UNASSIGNED: ClinicalTrials.gov Identifiers: NCT03525600 and NCT03525613.