Institut de la Màcula, Barcelona, Spain, Barcelona Macula Foundation, Barcelona, Spain.
Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.
Ophthalmology. 2021 Jul;128(7):1050-1059. doi: 10.1016/j.ophtha.2020.11.011. Epub 2020 Nov 15.
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.
由诺华制药公司支持的独立安全审查委员会（SRC）分析了在湿性年龄相关性黄斑变性（nAMD）的 2 项为期 2 年、双盲、多中心、活性对照 3 期临床试验 HAWK 和 HARRIER 中，brolucizumab 与 aflibercept 比较的玻璃体腔内炎症（IOI）、眼内炎和视网膜动脉阻塞的研究者报告病例。
对两项 2 年、双盲、多中心、活性对照 3 期临床试验（NCT02307682，NCT02434328）中部分数据的事后分析。
在研究眼中患有未经治疗的、活动性脉络膜新生血管的患者（N=1817），这些患者患有年龄相关性黄斑变性，被随机分配并在 HAWK/HARRIER 中接受治疗。SRC 审查了研究者报告的 IOI（60/1088 例 brolucizumab 治疗眼；8/729 aflibercept 治疗眼）的病例数据。
SRC 收到了所有研究者确定的 IOI、视网膜动脉阻塞和眼内炎病例的详细信息和图像（眼底彩色照相、荧光素血管造影和 OCT）。至少有 2 位读者对病例进行了详细审查，然后由 SRC 作为一个小组进行裁决。
在该患者亚组中：IOI 的发生率、视网膜血管炎和/或视网膜血管阻塞的迹象和发生率，以及视力丧失；从第一次 brolucizumab 注射到 IOI 事件发作的时间；以及首次 IOI 事件发作时 brolucizumab 注射后的视力丧失频率。
50 只接受 brolucizumab 治疗的眼睛被认为具有明确/可能与药物相关的 IOI、视网膜血管炎和/或血管阻塞范围内的事件。基于这些病例，明确/可能 IOI 的发生率为 4.6%（IOI+血管炎，3.3%；IOI+血管炎+阻塞，2.1%）。在 IOI 患者中有 8 例（发生率为 0.74%）发生至少中度视力丧失（≥15 ETDRS 字母）（7 例在 IOI+血管炎+阻塞的患者中）。在 8 例患者中，有 5 例在首次 brolucizumab 注射后 3 个月内发生首次与 IOI 相关的事件（在 6 个月内增加到 7/8）。在 aflibercept 治疗的眼睛中，IOI 的发生率为 1.1%，至少有中度视力丧失的发生率为 0.14%。
对 brolucizumab 注射后 IOI 病例的分析确定了伴有或不伴有视网膜血管阻塞的视网膜血管炎的迹象，并伴有视力丧失的风险。这些发现将有助于医生评估 brolucizumab 治疗 nAMD 的风险和获益。
