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

John W. Kitchens, Diana V. Do, David S. Boyer, Desmond Thompson, Andrea Gibson, Namrata Saroj, Robert Vitti, Alyson J. Berliner, Peter K. Kaiser

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Purpose 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.

Original languageEnglish (US)
Pages (from-to)1511-1520
Number of pages10
JournalOphthalmology
Volume123
Issue number7
DOIs
StatePublished - Jul 1 2016

Fingerprint

Intravitreal Injections
Randomized Controlled Trials
Safety
Macular Edema
Retinal Vein Occlusion
Confidence Intervals
Macular Degeneration
Retinal Vein
Endophthalmitis
aflibercept
Hypertension
Wound Healing
Blood Platelets
Inflammation
Retinal Diseases

Keywords

  • ATE arterial thromboembolic event
  • Abbreviations and Acronyms APTC Anti-Platelet Trialists Collaboration
  • 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
  • PYR person-year at risk
  • RR rate ratio
  • SA sensitivity analysis
  • SAE serious adverse event
  • VEGF vascular endothelial growth factor
  • nAMD neovascular age-related macular degeneration

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Kitchens, J. W., Do, D. V., Boyer, D. S., Thompson, D., Gibson, A., Saroj, N., ... Kaiser, P. K. (2016). Comprehensive Review of Ocular and Systemic Safety Events with Intravitreal Aflibercept Injection in Randomized Controlled Trials. Ophthalmology, 123(7), 1511-1520. https://doi.org/10.1016/j.ophtha.2016.02.046

Comprehensive Review of Ocular and Systemic Safety Events with Intravitreal Aflibercept Injection in Randomized Controlled Trials. / Kitchens, John W.; Do, Diana V.; Boyer, David S.; Thompson, Desmond; Gibson, Andrea; Saroj, Namrata; Vitti, Robert; Berliner, Alyson J.; Kaiser, Peter K.

In: Ophthalmology, Vol. 123, No. 7, 01.07.2016, p. 1511-1520.

Research output: Contribution to journalArticle

Kitchens, JW, Do, DV, Boyer, DS, Thompson, D, Gibson, A, Saroj, N, Vitti, R, Berliner, AJ & Kaiser, PK 2016, 'Comprehensive Review of Ocular and Systemic Safety Events with Intravitreal Aflibercept Injection in Randomized Controlled Trials', Ophthalmology, vol. 123, no. 7, pp. 1511-1520. https://doi.org/10.1016/j.ophtha.2016.02.046
Kitchens, John W. ; Do, Diana V. ; Boyer, David S. ; Thompson, Desmond ; Gibson, Andrea ; Saroj, Namrata ; Vitti, Robert ; Berliner, Alyson J. ; Kaiser, Peter K. / Comprehensive Review of Ocular and Systemic Safety Events with Intravitreal Aflibercept Injection in Randomized Controlled Trials. In: Ophthalmology. 2016 ; Vol. 123, No. 7. pp. 1511-1520.
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title = "Comprehensive Review of Ocular and Systemic Safety Events with Intravitreal Aflibercept Injection in Randomized Controlled Trials",
abstract = "Purpose 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.",
keywords = "ATE arterial thromboembolic event, Abbreviations and Acronyms APTC Anti-Platelet Trialists Collaboration, 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, PYR person-year at risk, RR rate ratio, SA sensitivity analysis, SAE serious adverse event, VEGF vascular endothelial growth factor, nAMD neovascular age-related macular degeneration",
author = "Kitchens, {John W.} and Do, {Diana V.} and Boyer, {David S.} and Desmond Thompson and Andrea Gibson and Namrata Saroj and Robert Vitti and Berliner, {Alyson J.} and Kaiser, {Peter K.}",
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TY - JOUR

T1 - Comprehensive Review of Ocular and Systemic Safety Events with Intravitreal Aflibercept Injection in Randomized Controlled Trials

AU - Kitchens, John W.

AU - Do, Diana V.

AU - Boyer, David S.

AU - Thompson, Desmond

AU - Gibson, Andrea

AU - Saroj, Namrata

AU - Vitti, Robert

AU - Berliner, Alyson J.

AU - Kaiser, Peter K.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Purpose 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.

AB - Purpose 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.

KW - ATE arterial thromboembolic event

KW - Abbreviations and Acronyms APTC Anti-Platelet Trialists Collaboration

KW - BRVO branch retinal vein occlusion

KW - CI confidence interval

KW - CRVO central retinal vein occlusion

KW - DME diabetic macular edema

KW - HTN hypertension

KW - IAI intravitreal aflibercept injection

KW - MEfBRVO macular edema following branch retinal vein occlusion

KW - MEfCRVO macular edema following central retinal vein occlusion

KW - PYR person-year at risk

KW - RR rate ratio

KW - SA sensitivity analysis

KW - SAE serious adverse event

KW - VEGF vascular endothelial growth factor

KW - nAMD neovascular age-related macular degeneration

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