Retina Associates of Kentucky, Lexington, Kentucky.
Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, Nebraska.
Ophthalmology. 2016 Jul;123(7):1511-20. doi: 10.1016/j.ophtha.2016.02.046. Epub 2016 Apr 12.
To assess the ocular and systemic safety of intravitreal aflibercept injection (IAI) compared with controls in IAI trials in neovascular age-related macular degeneration (nAMD), macular edema following central retinal vein occlusion (MEfCRVO), macular edema following branch retinal vein occlusion (MEfBRVO), and diabetic macular edema (DME).
Comprehensive review of 10 phase II and III trials of IAI in retinal diseases.
Patients were included from IAI trials in nAMD (CLEAR-IT 2 [52 weeks], VIEW 1 [96 weeks], VIEW 2 [96 weeks], VIEW 1 extension [208 weeks]); MEfCRVO (COPERNICUS [100 weeks], GALILEO [76 weeks]); MEfBRVO (VIBRANT [52 weeks]); and DME (DA VINCI [52 weeks], VIVID [100 weeks], VISTA [100 weeks]).
Rates were calculated as events/100 person-years at risk (PYR). When applicable, rate ratios (RRs) and 95% confidence intervals (CIs) were provided.
Outcomes included rates for intraocular inflammation, endophthalmitis, serious adverse events (SAEs), wound-healing complications, hypertension (HTN), adjudicated Anti-Platelet Trialists' Collaboration (APTC)-defined arterial thromboembolic events (ATEs) (nonfatal myocardial infarction, nonfatal stroke, and vascular death), and death from all causes.
More than 4000 patients contributed >7000 PYR. For all outcomes, there were no meaningful differences between evaluated adverse event rates for IAI and controls. Overall intraocular inflammation rates were 2.37 (control) and 2.06 (IAI); overall RR was 0.87 (95% CI, 0.61-1.27). Overall endophthalmitis rates were 0.52 (control) and 0.22 (IAI); overall RR was 0.42 (95% CI, 0.18-1.03). Overall SAE rates were 23.09 (control) and 20.80 (IAI); overall RR was 0.90 (95% CI, 0.80-1.02). Overall rates of wound-healing complications were 0.17 (control) and 0.15 (IAI); overall RR was 0.85 (95% CI, 0.24-3.86). Overall HTN rates were 14.87 (control) and 11.27 (IAI), with an overall RR of 0.76 (95% CI, 0.65-0.89); HTN rates were highest in MEfBRVO and lowest in nAMD. For adjudicated APTC-defined ATEs, rates were 2.04 (control) and 2.19 (IAI), with an RR of 1.07 (95% CI, 0.73-1.61). Overall death rates were 1.16 (control) and 1.49 (IAI); overall RR was 1.28 (95% CI, 0.80-2.15).
Rates of selected ocular and systemic adverse events with IAI were similar to those of controls and similar across disease states in evaluated IAI trials. Intravitreal aflibercept injection was generally well tolerated in the patients evaluated.
评估玻璃体内注射阿柏西普（IAI）与对照相比在新生血管性年龄相关性黄斑变性（nAMD）、视网膜中央静脉阻塞（CRVO）继发黄斑水肿（MEfCRVO）、视网膜分支静脉阻塞（BRVO）继发黄斑水肿（MEfBRVO）和糖尿病性黄斑水肿（DME）的眼部和全身安全性。
对 10 项视网膜疾病 II 期和 III 期 IAI 试验进行综合回顾。
纳入了 nAMD（CLEAR-IT 2 [52 周]、VIEW 1 [96 周]、VIEW 2 [96 周]、VIEW 1 扩展 [208 周]）、MEfCRVO（COPERNICUS [100 周]、GALILEO [76 周]）、MEfBRVO（VIBRANT [52 周]）和 DME（DA VINCI [52 周]、VIVID [100 周]、VISTA [100 周]）的 IAI 试验中的患者。
按每 100 人年风险（PYR）计算发生率。在适用的情况下，提供了率比（RR）和 95%置信区间（CI）。
结局包括眼内炎症、眼内炎、严重不良事件（SAE）、伤口愈合并发症、高血压（HTN）、血小板试验者协作组（APTC）定义的动脉血栓栓塞事件（ATEs）（非致死性心肌梗死、非致死性卒中和血管性死亡）和所有原因导致的死亡发生率。
超过 4000 名患者提供了 >7000 PYR。对于所有结局，与对照相比，评估的不良事件发生率均无显著差异。总体眼内炎症发生率为 2.37（对照）和 2.06（IAI）；总 RR 为 0.87（95%CI，0.61-1.27）。总体眼内炎发生率为 0.52（对照）和 0.22（IAI）；总 RR 为 0.42（95%CI，0.18-1.03）。总体 SAE 发生率为 23.09（对照）和 20.80（IAI）；总 RR 为 0.90（95%CI，0.80-1.02）。总体伤口愈合并发症发生率为 0.17（对照）和 0.15（IAI）；总 RR 为 0.85（95%CI，0.24-3.86）。总体 HTN 发生率为 14.87（对照）和 11.27（IAI），总 RR 为 0.76（95%CI，0.65-0.89）；HTN 发生率在 MEfBRVO 中最高，在 nAMD 中最低。对于 APTC 定义的 ATEs，发生率为 2.04（对照）和 2.19（IAI），RR 为 1.07（95%CI，0.73-1.61）。总体死亡率为 1.16（对照）和 1.49（IAI）；总 RR 为 1.28（95%CI，0.80-2.15）。
与对照相比，IAI 治疗的眼部和全身不良事件发生率相似，且在评估的 IAI 试验中在不同疾病状态下相似。玻璃体内注射阿柏西普在评估的患者中总体耐受良好。
