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Clinical effectiveness of intravitreal therapy with ranibizumab vs aflibercept vs vevacizumab for macular edema secondary to central retinal vein occlusion: A randomized clinical trial

Clinical effectiveness of intravitreal therapy with ranibizumab vs aflibercept vs vevacizumab for macular edema secondary to central retinal vein occlusion: A randomized clinical trial
Clinical effectiveness of intravitreal therapy with ranibizumab vs aflibercept vs vevacizumab for macular edema secondary to central retinal vein occlusion: A randomized clinical trial
Importance:  The comparative clinical effectiveness of ranibizumab, aflibercept, and bevacizumab for the management of macular edema due to central retinal vein occlusion (CRVO) is unclear.
Objective:  To determine whether intravitreal aflibercept or bevacizumab compared with ranibizumab results in a noninferior mean change in vision at 100 weeks for eyes with CRVO-related macular edema.
Design, Setting, and Participants: This prospective, 3-arm, double-masked, randomized noninferiority trial (Lucentis, Eylea, Avastin in Vein Occlusion [LEAVO] Study) took place from December 12, 2014, through December 16, 2016, at 44 UK National Health Service ophthalmology departments. Inclusion criteria included age 18 years or older, visual impairment due to CRVO-related macular edema of less than 12 months with best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study letter score (approximate Snellen equivalent) in the study eye between 19 (20/400) and 78 (20/32), and spectral domain optical coherence tomography imaging central subfield thickness of 320 μm or greater. Data were analyzed from March 4, 2019, to April 26, 2019.
Interventions: Participants were randomized (1:1:1) to receive repeated intravitreal injections of ranibizumab (0.5 mg/0.05 mL) (n = 155), aflibercept (2.0 mg/0.05 mL) (n = 154), or bevacizumab (1.25 mg/0.05 mL) (n = 154) for 100 weeks.
Main Outcomes and Measures: Adjusted mean change in BCVA in the study eye at 100 weeks wherein noninferiority was concluded if the lower bounds of the 95% CI of both the intention-to-treat and the per protocol analyses were above –5 letters.
Results: Of 463 participants, 265 (57.2%) were male, with a mean (SD) age of 69.1 (13.0) years. The mean (SD) gain in BCVA letter score was 12.5 (21.1) for ranibizumab, 15.1 (18.7) for aflibercept, and 9.8 (21.4) for bevacizumab at 100 weeks. Aflibercept was noninferior to ranibizumab (intention-to-treat–adjusted mean BCVA difference, 2.23 letters; 95% CI, –2.17 to 6.63 letters; P < .001). Bevacizumab was not noninferior to ranibizumab (intention-to-treat–adjusted mean BCVA difference, –1.73 letters; 95% CI, –6.12 to 2.67 letters; P = .07). The per protocol analysis conclusions were similar. Fewer mean injections were given in the aflibercept group (10.0) than in the ranibizumab (11.8) group (mean difference at 100 weeks, –1.9; 95% CI, –2.9 to –0.8).
Conclusions and Relevance: Mean changes in vision after treatment of macular edema due to CRVO were no worse using aflibercept compared with ranibizumab. Mean changes in vision using bevacizumab compared with ranibizumab were inconclusive regarding vision outcomes (ie, the change in visual acuity from baseline, on average, may be worse or may not be worse when using bevacizumab compared with ranibizumab).
2168-6165
Hykin, Philip
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Prevost, A. Toby
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Vasconcelos, Joana
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Murphy, Caroline
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Kelly, Joanne
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Ramu, Jayashree
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Hounsome, Barry
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Yang, Yit
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Harding, Simon P.
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Lotery, Andrew
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Chakravarthy, Usha
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Sivaprasad, Sobha
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Hykin, Philip
668bf80b-3b95-4522-9ff0-8303a692b77b
Prevost, A. Toby
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Vasconcelos, Joana
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Murphy, Caroline
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Kelly, Joanne
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Ramu, Jayashree
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Hounsome, Barry
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Yang, Yit
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Harding, Simon P.
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Lotery, Andrew
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Chakravarthy, Usha
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Sivaprasad, Sobha
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Hykin, Philip, Prevost, A. Toby, Vasconcelos, Joana, Murphy, Caroline, Kelly, Joanne, Ramu, Jayashree, Hounsome, Barry, Yang, Yit, Harding, Simon P., Lotery, Andrew, Chakravarthy, Usha and Sivaprasad, Sobha (2019) Clinical effectiveness of intravitreal therapy with ranibizumab vs aflibercept vs vevacizumab for macular edema secondary to central retinal vein occlusion: A randomized clinical trial. JAMA Ophthalmology. (doi:10.1001/jamaophthalmol.2019.3305).

Record type: Article

Abstract

Importance:  The comparative clinical effectiveness of ranibizumab, aflibercept, and bevacizumab for the management of macular edema due to central retinal vein occlusion (CRVO) is unclear.
Objective:  To determine whether intravitreal aflibercept or bevacizumab compared with ranibizumab results in a noninferior mean change in vision at 100 weeks for eyes with CRVO-related macular edema.
Design, Setting, and Participants: This prospective, 3-arm, double-masked, randomized noninferiority trial (Lucentis, Eylea, Avastin in Vein Occlusion [LEAVO] Study) took place from December 12, 2014, through December 16, 2016, at 44 UK National Health Service ophthalmology departments. Inclusion criteria included age 18 years or older, visual impairment due to CRVO-related macular edema of less than 12 months with best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study letter score (approximate Snellen equivalent) in the study eye between 19 (20/400) and 78 (20/32), and spectral domain optical coherence tomography imaging central subfield thickness of 320 μm or greater. Data were analyzed from March 4, 2019, to April 26, 2019.
Interventions: Participants were randomized (1:1:1) to receive repeated intravitreal injections of ranibizumab (0.5 mg/0.05 mL) (n = 155), aflibercept (2.0 mg/0.05 mL) (n = 154), or bevacizumab (1.25 mg/0.05 mL) (n = 154) for 100 weeks.
Main Outcomes and Measures: Adjusted mean change in BCVA in the study eye at 100 weeks wherein noninferiority was concluded if the lower bounds of the 95% CI of both the intention-to-treat and the per protocol analyses were above –5 letters.
Results: Of 463 participants, 265 (57.2%) were male, with a mean (SD) age of 69.1 (13.0) years. The mean (SD) gain in BCVA letter score was 12.5 (21.1) for ranibizumab, 15.1 (18.7) for aflibercept, and 9.8 (21.4) for bevacizumab at 100 weeks. Aflibercept was noninferior to ranibizumab (intention-to-treat–adjusted mean BCVA difference, 2.23 letters; 95% CI, –2.17 to 6.63 letters; P < .001). Bevacizumab was not noninferior to ranibizumab (intention-to-treat–adjusted mean BCVA difference, –1.73 letters; 95% CI, –6.12 to 2.67 letters; P = .07). The per protocol analysis conclusions were similar. Fewer mean injections were given in the aflibercept group (10.0) than in the ranibizumab (11.8) group (mean difference at 100 weeks, –1.9; 95% CI, –2.9 to –0.8).
Conclusions and Relevance: Mean changes in vision after treatment of macular edema due to CRVO were no worse using aflibercept compared with ranibizumab. Mean changes in vision using bevacizumab compared with ranibizumab were inconclusive regarding vision outcomes (ie, the change in visual acuity from baseline, on average, may be worse or may not be worse when using bevacizumab compared with ranibizumab).

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Accepted/In Press date: 8 July 2019
Published date: 29 August 2019

Identifiers

Local EPrints ID: 433978
URI: http://eprints.soton.ac.uk/id/eprint/433978
ISSN: 2168-6165
PURE UUID: daf3415c-acfb-4109-b950-532ff11ffead
ORCID for Andrew Lotery: ORCID iD orcid.org/0000-0001-5541-4305

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Date deposited: 09 Sep 2019 16:30
Last modified: 26 Nov 2021 02:47

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Contributors

Author: Philip Hykin
Author: A. Toby Prevost
Author: Joana Vasconcelos
Author: Caroline Murphy
Author: Joanne Kelly
Author: Jayashree Ramu
Author: Barry Hounsome
Author: Yit Yang
Author: Simon P. Harding
Author: Andrew Lotery ORCID iD
Author: Usha Chakravarthy
Author: Sobha Sivaprasad

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