First-Line Bevacizumab Cost-Effective for Macular Edema Due to CRVO or HRVO

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An economic evaluation of the SCORE2 trial indicates aflibercept treatment was unlikely to meet most accepted standards of cost-effectiveness, due to little difference in visual acuity outcomes and a large cost differential compared with bevacizumab.

Due to minimal differences in visual acuity outcomes, but large cost differences, a new economic evaluation study suggested first-line treatment with bevacizumab is more cost-effective than aflibercept in the treatment of macular edema associated with central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO).1

According to the simulation’s findings, patients with macular edema secondary to CRVO or HRVO undergoing aflibercept treatment would have an expected cost of $18,127 greater than those treated with bevacizumab in the year following initiation.

“While there may be some subgroups of patients who will derive the most benefit from first-line treatment with aflibercept, it is likely a small fraction of those living with CRVO or HRVO,” wrote the investigative team, led by Paul C. VanVeldhuisen, PhD from The Emmes Company.

Vision loss from RVO is most often due to macular edema and has been a therapeutic target area of anti-vascular endothelial growth factor (anti-VEGF) treatment. Previously. the US Food and Drug Administration (FDA) approved aflibercept for the treatment of macular edema following RVO in October 2014.2 Off-label use of bevacizumab is widespread, due to its low-cost relative to other anti-VEGF agents, and its efficacy and safety profile demonstrated for patients with age-related macular degeneration (AMD) and diabetic macular edema (DME).

Results from the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2) trial suggested the noninferiority of bevacizumab to aflibercept regarding visual acuity in patients with macular edema due to CRVO or HRVO after 6 months of therapy. However, despite these findings and the lower cost of bevacizumab, physicians may still choose aflibercept as a first-line treatment for RVO. To further explore the insights into circumstances in which aflibercept may be preferable as a first-line treatment, VanVeldhuisen and colleagues performed an economic evaluation of bevacizumab versus aflibercept based on the SCORE2 trial.

“While the results of the SCORE2 study, when juxtaposed to the relatively high cost of aflibercept, may make the results of our study self-evident, we conducted this study to gain insights into the nuances of the cost-benefit relationship in the treatment of CRVO and HRVO,” investigators wrote.

The analysis utilized an economic model comparing competing 2 competing treatment approaches: initiate treatment with bevacizumab and if the patient demonstrated a protocol-defined poor or marginal treatment response after 6 monthly injections, switch to aflibercept; or, initiate treatment with aflibercept and if the patient demonstrates a poor or marginal response after 6 monthly injections, switch to dexamethasone implant.

In order to assess their relative cost-effectiveness, investigators used a microsimulation cohort of 5000 patients based on SCORE2 data. The parameters of the model were developed using a split-sample approach, with the SCORE2 sample divided in half. SCORE2 data were collected from September 2014 - October 2019 and data were analyzed from October 2019 - July 2021.

Costs included in the model were limited to those associated with medication and administration due to a lack of standard, with $150 used per dose for bevacizumab, $1941 per dose for aflibercept, and $1650 per implant for dexamethasone. Investigators measured quality of life using utility, measured on a scale of 0.0 (comparable with death) to 1.0 (perfect health), and reported quality-adjusted life-years (QALYs).

Upon analysis, simulated patients treated with bevacizumab experienced a visual acuity letter score (VALS) improvement of 22 in the treated eye, while those treated with aflibercept experienced a VALS improvement of 18. The economic model indicated that patients who initiated bevacizumab therapy accrued a cost of $3213 through 1 year of treatment and experienced gain of 0.026 QALYs. Those who initiated aflibercept accrued a 12-month cost of $21,340 (an increase of $18,127 vs. bevacizumab) with a QALY improvement of 0.020 QALYs.

Since bevacizumab is less expensive and more effective than aflibercept in terms of QALYs, investigators considered bevacizumab dominant compared with aflibercept in the model. Considering the small differences in QALYs, they noted the differences may be due to random variation in visual acuity rather than effectiveness. As a result, investigators assumed the dominance is a result of the difference in the cost of treatment rather than its effectiveness.

Sensitivity analyses revealed no clinically relevant changes in parameter values favoring aflibercept as a first-line treatment from a cost-effectiveness perspective. Data showed the difference in effectiveness required to justify the cost difference would need to be 0.12 QALY per year favoring aflibercept treatment over the current value of 0.006 QALY per year favoring bevacizumab.

“To achieve this level of improvement would require that the treated eye become nearly perfect in its vision, something that is clearly not clinically achievable,” investigators wrote.


  1. Kymes SM, Oden NL, VanVeldhuisen PC, et al. Cost-Utility Comparison of Bevacizumab and Aflibercept in the Treatment of Central or Hemiretinal Vein Occlusion in the SCORE2 Trial. JAMA Ophthalmol. Published online May 11, 2023. doi:10.1001/jamaophthalmol.2023.1463
  2. Eylea (Aflibercept) injection receives FDA approval for the treatment of macular edema following retinal vein occlusion (RVO). News release. Regeneron. October 6, 2014. Accessed May 18, 2023.