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


METHODS
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.


METHODS
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
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.
Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor2Department of Health Management and Policy, University of Michigan School of Public Health, Ann Arbor.
Eric L
EL
Ross
Department of Health Management and Policy, University of Michigan School of Public Health, Ann Arbor3Department of Industrial and Operations Engineering, University of Michigan College of Engineering, Ann Arbor4Institute for Healthcare Policy and Innovat.
David W
DW
Hutton
Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor2Department of Health Management and Policy, University of Michigan School of Public Health, Ann Arbor4Institute for Healthcare Policy and Innovation, Univers.
Joshua D
JD
Stein
Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland6Editor, JAMA Ophthalmology.
Neil M
NM
Bressler
Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
Lee M
LM
Jampol
Jaeb Center for Health Research, Tampa, Florida.
Adam R
AR
Glassman
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000191:economics; D003930:Diabetic Retinopathy / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D016527:Drug Costs; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D017048:Health Care Costs; D006801:Humans; D058449:Intravitreal Injections; D008269:Macular Edema / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D019057:Quality-Adjusted Life Years; D000069579:Ranibizumab / Q000008:administration & dosage* / Q000191:economics; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000191:economics; D012189:Retrospective Studies; D013997:Time Factors; D014792:Visual Acuity
D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; C533178:aflibercept; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor; D000069579:Ranibizumab