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Original Investigation |

Cost-effectiveness of Aflibercept, Bevacizumab, and Ranibizumab for Diabetic Macular Edema Treatment Analysis From the Diabetic Retinopathy Clinical Research Network Comparative Effectiveness Trial

Eric L. Ross, BA1,2; David W. Hutton, PhD2,3,4; Joshua D. Stein, MD, MS1,2,4; Neil M. Bressler, MD5,6; Lee M. Jampol, MD7; Adam R. Glassman, MS8 ; for the Diabetic Retinopathy Clinical Research Network
[+] Author Affiliations
1Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor
2Department of Health Management and Policy, University of Michigan School of Public Health, Ann Arbor
3Department of Industrial and Operations Engineering, University of Michigan College of Engineering, Ann Arbor
4Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor
5Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland
6Editor, JAMA Ophthalmology
7Feinberg School of Medicine, Northwestern University, Chicago, Illinois
8Jaeb Center for Health Research, Tampa, Florida
JAMA Ophthalmol. 2016;134(8):888-896. doi:10.1001/jamaophthalmol.2016.1669.
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Importance  Anti–vascular endothelial growth factor (VEGF) medicines have revolutionized diabetic macular edema (DME) treatment. A recent randomized clinical trial comparing anti-VEGF agents for patients with decreased vision from DME found that at 1 year aflibercept (2.0 mg) achieved better visual outcomes than repackaged (compounded) bevacizumab (1.25 mg) or ranibizumab (0.3 mg); the worse the starting vision, the greater the treatment benefit with aflibercept. However, aflibercept and ranibizumab, respectively, are approximately 31 and 20 times more expensive than bevacizumab.

Objective  To examine the incremental cost-effectiveness ratios (ICERs) of aflibercept, bevacizumab, and ranibizumab for the treatment of DME.

Design, Setting, and Participants  Post hoc analysis of efficacy, safety, and resource utilization data at 1-year follow-up from the Diabetic Retinopathy Clinical Research Network Comparative Effectiveness Trial. Patients were enrolled from August 22, 2012, through August 28, 2013, and analysis was performed from August 21, 2014, through November 7, 2015.

Main Outcomes and Measures  The ICERs for all trial participants and subgroups with baseline vision of approximate Snellen equivalent 20/32 to 20/40 (better vision) and baseline vision of approximate Snellen equivalent 20/50 or worse (worse vision). One-year trial data were used to calculate cost-effectiveness for 1 year for the 3 anti-VEGF agents; mathematical modeling was then used to project 10-year cost-effectiveness results.

Results  The study included 624 participants (mean [SD] age, 60.6 [10.5] years; 45.7% female; 65.5% white), 209 in the aflibercept group, 207 in the bevacizumab group, and 208 in the ranibizumab group. For all participants, during 1 year, the ICERs of aflibercept and ranibizumab compared with bevacizumab were $1 110 000 per quality-adjusted life-year (QALY) and $1 730 000 per QALY, respectively. During 10 years, they were $349 000 per QALY and $603 000 per QALY, respectively. Compared with ranibizumab, aflibercept’s ICER was $648 000 per QALY at 1 year and $203 000 per QALY at 10 years. For the subgroup with worse baseline vision, the 10-year ICERs of aflibercept and ranibizumab compared with bevacizumab were $287 000 per QALY and $817 000 per QALY, respectively. In eyes with decreased vision from DME, treatment costs of aflibercept and ranibizumab would need to decrease by 69% and 80%, respectively, to reach a cost-effectiveness threshold of $100 000 per QALY compared with bevacizumab during a 10-year horizon; for the subgroup with worse baseline vision, the costs would need to decrease by 62% and 84%, respectively.

Conclusions and Relevance  Aflibercept (2.0 mg) and ranibizumab (0.3 mg) are not cost-effective relative to bevacizumab for treatment of DME unless their prices decrease substantially. These results highlight the challenges that physicians, patients, and policymakers face when safety and efficacy results are at odds with cost-effectiveness results.

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Figure 1.
Costs During 1 Year Divided Into Study and Nonstudy Eye Anti–Vascular Endothelial Growth Factor (VEGF) Injections Separately, Laser Photocoagulation, and Adverse Events

Costs are presented for all participants and the worse and better visual acuity (VA) subgroups. Anti-VEGF injections include the agent costs and a $102.97 fee per injection.

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Figure 2.
The Aflibercept-Bevacizumab Incremental Cost-effectiveness Ratio (ICER) for Varying Assumptions for Visual Acuity (VA) Changes in 10 Years

The changing color indicates the 10-year ICER based on VA change with each drug. BCVA indicates best-corrected VA; ETDRS, Early Treatment Diabetic Retinopathy Study letter score.

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