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Change in Diabetic Retinopathy Through 2 Years: Secondary Analysis of a Randomized Clinical Trial Comparing Aflibercept, Bevacizumab, and Ranibizumab.
JAMA Ophthalmol. 2017 06 01; 135(6):558-568.JO

Abstract

Importance

Anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME) favorably affects diabetic retinopathy (DR) improvement and worsening. It is unknown whether these effects differ across anti-VEGF agents.

Objective

To compare changes in DR severity during aflibercept, bevacizumab, or ranibizumab treatment for DME.

Design, Setting, and Participants

Preplanned secondary analysis of data from a comparative effectiveness trial for center-involved DME was conducted in 650 participants receiving aflibercept, bevacizumab, or ranibizumab. Retinopathy improvement and worsening were determined during 2 years of treatment. Participants were randomized in 2012 through 2013, and the trial concluded on September 23, 2015.

Interventions

Random assignment to aflibercept, 2.0 mg; bevacizumab, 1.25 mg; ranibizumab, 0.3 mg, up to every 4 weeks through 2 years following a retreatment protocol.

Main Outcomes and Measures

Percentages with retinopathy improvement at 1 and 2 years and cumulative probabilities for retinopathy worsening through 2-year without adjustment for multiple outcomes.

Results

A total of 650 participants (495 [76.2%] nonproliferative DR [NPDR], 155 proliferative DR [PDR]) were analyzed; 302 (46.5%) were women and mean (SD) age was 61 (10) years; 425 (65.4%) were white. At 1 year, among 423 NPDR eyes, 44 of 141 (31.2%) treated with aflibercept, 29 of 131 (22.1%) with bevacizumab, and 57 of 151 (37.7%) with ranibizumab had improvement of DR severity (adjusted difference: 11.7%; 95% CI, 2.9% to 20.6%; P = .004 for aflibercept vs bevacizumab; 8.9%; 95% CI, 1.7% to 16.1%; P = .01 for ranibizumab vs bevacizumab; and 2.9%; 95% CI, -5.7% to 11.4%; P = .51 for aflibercept vs ranibizumab). At 2 years, 33 eyes (24.8%) in the aflibercept group, 25 eyes (22.1%) in the bevacizumab group, and 40 eyes (31.0%) in the ranibizumab group had DR improvement; no treatment group differences were identified. For 93 eyes with PDR at baseline, 1-year improvement rates were 75.9% for aflibercept, 31.4% for bevacizumab, and 55.2% for ranibizumab (adjusted difference: 50.4%; 95% CI, 26.8% to 74.0%; P < .001 for aflibercept vs bevacizumab; 20.4%; 95% CI, -3.1% to 44.0%; P = .09 for ranibizumab vs bevacizumab; and 30.0%; 95% CI, 4.4% to 55.6%; P = .02 for aflibercept vs ranibizumab). These rates and treatment group differences appeared to be maintained at 2 years. Despite the reduced numbers of injections in the second year, 66 (59.5%) of NPDR and 28 (70.0%) of PDR eyes that manifested improvement at 1 year maintained improvement at 2 years. Two-year cumulative rates for retinopathy worsening ranged from 7.1% to 10.2% and 17.2% to 26.4% among anti-VEGF groups for NPDR and PDR eyes, respectively. No statistically significant treatment differences were noted.

Conclusions and Relevance

At 1 and 2 years, eyes with NPDR receiving anti-VEGF treatment for DME may experience improvement in DR severity. Less improvement was demonstrated with bevacizumab at 1 year than with aflibercept or ranibizumab. Aflibercept was associated with more improvement at 1 and 2 years in the smaller subgroup of participants with PDR at baseline. All 3 anti-VEGF treatments were associated with low rates of DR worsening. These data provide additional outcomes that might be considered when choosing an anti-VEGF agent to treat DME.

Authors+Show Affiliations

Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.Jaeb Center for Health Research, Tampa, Florida.Jaeb Center for Health Research, Tampa, Florida.Fundus Photograph Reading Center, University of Wisconsin, Madison.California Retina Consultants and Research Foundation, Santa Barbara.Feinberg School of Medicine, Northwestern University, Chicago, Illinois.Thomas Eye Group, Atlanta, Georgia.Jaeb Center for Health Research, Tampa, Florida.Southeast Retina Center, PC, Augusta, Georgia.Palmetto Retina Center, Columbia, South Carolina.No affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

28448655

Citation

Bressler, Susan B., et al. "Change in Diabetic Retinopathy Through 2 Years: Secondary Analysis of a Randomized Clinical Trial Comparing Aflibercept, Bevacizumab, and Ranibizumab." JAMA Ophthalmology, vol. 135, no. 6, 2017, pp. 558-568.
Bressler SB, Liu D, Glassman AR, et al. Change in Diabetic Retinopathy Through 2 Years: Secondary Analysis of a Randomized Clinical Trial Comparing Aflibercept, Bevacizumab, and Ranibizumab. JAMA Ophthalmol. 2017;135(6):558-568.
Bressler, S. B., Liu, D., Glassman, A. R., Blodi, B. A., Castellarin, A. A., Jampol, L. M., Kaufman, P. L., Melia, M., Singh, H., & Wells, J. A. (2017). Change in Diabetic Retinopathy Through 2 Years: Secondary Analysis of a Randomized Clinical Trial Comparing Aflibercept, Bevacizumab, and Ranibizumab. JAMA Ophthalmology, 135(6), 558-568. https://doi.org/10.1001/jamaophthalmol.2017.0821
Bressler SB, et al. Change in Diabetic Retinopathy Through 2 Years: Secondary Analysis of a Randomized Clinical Trial Comparing Aflibercept, Bevacizumab, and Ranibizumab. JAMA Ophthalmol. 2017 06 1;135(6):558-568. PubMed PMID: 28448655.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Change in Diabetic Retinopathy Through 2 Years: Secondary Analysis of a Randomized Clinical Trial Comparing Aflibercept, Bevacizumab, and Ranibizumab. AU - Bressler,Susan B, AU - Liu,Danni, AU - Glassman,Adam R, AU - Blodi,Barbara A, AU - Castellarin,Alessandro A, AU - Jampol,Lee M, AU - Kaufman,Paul L, AU - Melia,Michele, AU - Singh,Harinderjit, AU - Wells,John A, AU - ,, PY - 2017/4/28/pubmed PY - 2017/7/20/medline PY - 2017/4/28/entrez SP - 558 EP - 568 JF - JAMA ophthalmology JO - JAMA Ophthalmol VL - 135 IS - 6 N2 - Importance: Anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME) favorably affects diabetic retinopathy (DR) improvement and worsening. It is unknown whether these effects differ across anti-VEGF agents. Objective: To compare changes in DR severity during aflibercept, bevacizumab, or ranibizumab treatment for DME. Design, Setting, and Participants: Preplanned secondary analysis of data from a comparative effectiveness trial for center-involved DME was conducted in 650 participants receiving aflibercept, bevacizumab, or ranibizumab. Retinopathy improvement and worsening were determined during 2 years of treatment. Participants were randomized in 2012 through 2013, and the trial concluded on September 23, 2015. Interventions: Random assignment to aflibercept, 2.0 mg; bevacizumab, 1.25 mg; ranibizumab, 0.3 mg, up to every 4 weeks through 2 years following a retreatment protocol. Main Outcomes and Measures: Percentages with retinopathy improvement at 1 and 2 years and cumulative probabilities for retinopathy worsening through 2-year without adjustment for multiple outcomes. Results: A total of 650 participants (495 [76.2%] nonproliferative DR [NPDR], 155 proliferative DR [PDR]) were analyzed; 302 (46.5%) were women and mean (SD) age was 61 (10) years; 425 (65.4%) were white. At 1 year, among 423 NPDR eyes, 44 of 141 (31.2%) treated with aflibercept, 29 of 131 (22.1%) with bevacizumab, and 57 of 151 (37.7%) with ranibizumab had improvement of DR severity (adjusted difference: 11.7%; 95% CI, 2.9% to 20.6%; P = .004 for aflibercept vs bevacizumab; 8.9%; 95% CI, 1.7% to 16.1%; P = .01 for ranibizumab vs bevacizumab; and 2.9%; 95% CI, -5.7% to 11.4%; P = .51 for aflibercept vs ranibizumab). At 2 years, 33 eyes (24.8%) in the aflibercept group, 25 eyes (22.1%) in the bevacizumab group, and 40 eyes (31.0%) in the ranibizumab group had DR improvement; no treatment group differences were identified. For 93 eyes with PDR at baseline, 1-year improvement rates were 75.9% for aflibercept, 31.4% for bevacizumab, and 55.2% for ranibizumab (adjusted difference: 50.4%; 95% CI, 26.8% to 74.0%; P < .001 for aflibercept vs bevacizumab; 20.4%; 95% CI, -3.1% to 44.0%; P = .09 for ranibizumab vs bevacizumab; and 30.0%; 95% CI, 4.4% to 55.6%; P = .02 for aflibercept vs ranibizumab). These rates and treatment group differences appeared to be maintained at 2 years. Despite the reduced numbers of injections in the second year, 66 (59.5%) of NPDR and 28 (70.0%) of PDR eyes that manifested improvement at 1 year maintained improvement at 2 years. Two-year cumulative rates for retinopathy worsening ranged from 7.1% to 10.2% and 17.2% to 26.4% among anti-VEGF groups for NPDR and PDR eyes, respectively. No statistically significant treatment differences were noted. Conclusions and Relevance: At 1 and 2 years, eyes with NPDR receiving anti-VEGF treatment for DME may experience improvement in DR severity. Less improvement was demonstrated with bevacizumab at 1 year than with aflibercept or ranibizumab. Aflibercept was associated with more improvement at 1 and 2 years in the smaller subgroup of participants with PDR at baseline. All 3 anti-VEGF treatments were associated with low rates of DR worsening. These data provide additional outcomes that might be considered when choosing an anti-VEGF agent to treat DME. SN - 2168-6173 UR - https://www.unboundmedicine.com/medline/citation/28448655/Change_in_Diabetic_Retinopathy_Through_2_Years:_Secondary_Analysis_of_a_Randomized_Clinical_Trial_Comparing_Aflibercept_Bevacizumab_and_Ranibizumab_ L2 - https://jamanetwork.com/journals/jamaophthalmology/fullarticle/10.1001/jamaophthalmol.2017.0821 DB - PRIME DP - Unbound Medicine ER -