Comprehensive Review of Ocular and Systemic Safety Events with Intravitreal Aflibercept Injection in Randomized Controlled Trials

详细信息    查看全文

• 作者：John W. Kitchens ; MD¹ ; Diana V. Do ; MD² ; David S. Boyer ; MD³ ; Desmond Thompson ; PhD⁴ ; Andrea Gibson ; PhD⁴ ; Namrata Saroj ; OD⁴ ; Robert Vitti ; MD⁴ ; Alyson J. Berliner ; MD ; PhD⁴ ; Peter K. Kaiser ; MD⁵ ; ^{pkkaiser@aol.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：APTC ; Anti-Platelet Trialists Collaboration ; ATE ; arterial thromboembolic event ; BRVO ; branch retinal vein occlusion ; CI ; confidence interval ; CRVO ; central retinal vein occlusion ; DME ; diabetic macular edema ; HTN ; hypertension ; IAI ; intravitreal aflibercept injection ; MEfBRVO ; macular edema following branch retinal vein occlusion ; MEfCRVO ; macular edema following central retinal vein occlusion ; nAMD ; neovascular age-related macular degeneration ; PYR ; person-year at risk ; RR ; rate ratio ; SA ; sen
• 刊名：Ophthalmology
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：123
• 期：7
• 页码：1511-1520
• 全文大小：1403 K

文摘

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).

Design

Comprehensive review of 10 phase II and III trials of IAI in retinal diseases.

Participants

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]).

Methods

Rates were calculated as events/100 person-years at risk (PYR). When applicable, rate ratios (RRs) and 95% confidence intervals (CIs) were provided.

Main Outcome Measures

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.

Results

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).

Conclusions

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.