独立安全审查委员会(SRC)由诺华制药公司支持,分析了研究者报告的眼内炎症(IOI)病例,眼内炎,在新生血管性年龄相关性黄斑变性(nAMD)的3期HAWK和HARRIER试验中,布罗珠单抗与阿柏西普的3期试验和视网膜动脉阻塞。
对两个两年期数据子集的事后分析,双面蒙面,多中心,主动对照随机3期试验(NCT02307682,NCT02434328)。
未经治疗的患者(N=1817),研究眼中年龄相关性黄斑变性引起的活动性脉络膜新生血管在HAWK/HARRIER治疗.SRC审查了研究者报告的IOI病例的数据(60/1088Brolucizumab治疗的眼睛;8/729阿柏西普治疗的眼睛)。
SRC收到了细节和图像(彩色眼底摄影,荧光素血管造影,和OCT)对于所有研究者确定的IOI病例,视网膜动脉阻塞,和眼内炎。病例由≥2名读者详细审查,然后由SRC作为一个团体裁定。
在该患者子集内:IOI的发生率,视网膜血管炎和/或视网膜血管阻塞的体征和发病率,和视力下降;从首次注射溴路珠单抗到IOI事件发作的时间;以及从首次IOI事件发作的时间开始,溴路珠单抗注射后视力下降的频率。
50只布卢珠单抗治疗的眼睛被认为在IOI范围内有明确/可能的药物相关事件,视网膜血管炎,和/或血管闭塞。根据这些案例,明确/可能的IOI的发生率为4.6%(IOI+血管炎,3.3%;IOI+血管炎+闭塞,2.1%)。IOI眼中有8例(发生率0.74%)至少中度视力下降(≥15个ETDRS字母)(IOI眼中有7例血管炎闭塞)。在这8个案例中,5例患者在首次注射brolucizumab后3个月内经历了首次IOI相关事件(6个月内增加至7/8)。在阿柏西普治疗的眼睛中IOI的发生率为1.1%,至少中度视力下降0.14%。
这项对布罗珠单抗注射后的IOI病例的分析确定了有或没有视网膜血管阻塞的视网膜血管炎的体征以及相关的视力丧失风险。这些发现将帮助医生评估brolucizumab治疗nAMD的风险和益处。
An independent Safety
Review Committee (SRC), supported by Novartis Pharma AG, analyzed investigator-reported cases of intraocular inflammation (IOI), endophthalmitis, and retinal arterial occlusion in the phase 3 HAWK and HARRIER trials of brolucizumab versus aflibercept in neovascular age-related macular degeneration (nAMD).
A post hoc analysis of a subset of data from two 2-year, double-masked, multicenter, active-controlled randomized phase 3 trials (NCT02307682, NCT02434328).
Patients (N = 1817) with untreated, active choroidal neovascularization due to age-related macular degeneration in the study eye were randomized and treated in HAWK/HARRIER. The SRC reviewed data from cases of investigator-reported IOI (60/1088 brolucizumab-treated eyes; 8/729 aflibercept-treated eyes).
The SRC received details and images (color fundus photography, fluorescein angiography, and OCT) for all investigator-determined cases of IOI, retinal arterial occlusion, and endophthalmitis. Cases were reviewed in detail by ≥2 readers, then adjudicated by the SRC as a group.
Within this patient subset: incidence of IOI, signs and incidence of retinal vasculitis and/or retinal vascular occlusion, and visual acuity loss; time since first brolucizumab injection to IOI event onset; and frequency of visual acuity loss after brolucizumab injection by time of first IOI event onset.
Fifty brolucizumab-treated eyes were considered to have definite/probable drug-related events within the spectrum of IOI, retinal vasculitis, and/or vascular occlusion. On the basis of these cases, incidence of definite/probable IOI was 4.6% (IOI + vasculitis, 3.3%; IOI + vasculitis + occlusion, 2.1%). There were 8 cases (incidence 0.74%) of at least moderate visual acuity loss (≥15 ETDRS letters) in eyes with IOI (7 in eyes with IOI + vasculitis + occlusion). Of the 8 cases, 5 experienced their first IOI-related event within 3 months of the first brolucizumab injection (increasing to 7/8 within 6 months). Incidence of IOI in aflibercept-treated eyes was 1.1%, with at least moderate visual acuity loss in 0.14%.
This analysis of IOI cases after brolucizumab injection identified signs of retinal vasculitis with or without retinal vascular occlusion and an associated risk of visual acuity loss. The findings will help physicians to evaluate the risks and benefits of brolucizumab treatment for nAMD.