Cost-effectiveness of bevacizumab and ranibizumab for newly diagnosed neovascular macular degeneration

Abstract

Purpose: We sought to determine the most cost-effective treatment for patients with newly diagnosed neovascular macular degeneration: monthly or as-needed bevacizumab injections, or monthly or as-needed ranibizumab injections.

Design: Cost-effectiveness analysis.

Participants: Hypothetical cohort of 80-year-old patients with newly diagnosed neovascular macular degeneration.

Methods: Using a mathematical model with a 20-year time horizon, we compared the incremental cost-effectiveness of treating a hypothetical cohort of 80-year-old patients with newly diagnosed neovascular macular degeneration using monthly bevacizumab, as-needed bevacizumab, monthly ranibizumab, or as-needed ranibizumab. Data came from the Comparison of Age-related macular degeneration Treatment Trial (CATT), the Medicare Fee Schedule, and the medical literature.

Main outcome measures: Costs, quality-adjusted life-years (QALYs), and incremental costs per QALY gained.

Results: Compared with as-needed bevacizumab, the incremental cost-effectiveness ratio of monthly bevacizumab is $24,2 357/QALY. Monthly ranibizumab gains an additional 0.02 QALYs versus monthly bevacizumab at an incremental cost-effectiveness ratio of >$10 million/QALY. As-needed ranibizumab was dominated by monthly bevacizumab, meaning it was more costly and less effective. In sensitivity analyses assuming a willingness to pay of $100,000/QALY, the annual risk of serious vascular events would have to be ≥2.5 times higher with bevacizumab than that observed in the CATT trial for as-needed ranibizumab to have an incremental cost-effectiveness ratio of <$100,000/QALY. In another sensitivity analysis, even if every patient receiving bevacizumab experienced declining vision by 1 category (e.g., from 20/25-20/40 to 20/50-20/80) after 2 years but every patient receiving ranibizumab retained their vision level, as-needed ranibizumab would have an incremental cost-effectiveness ratio of $97,340/QALY.

Conclusions: Even after considering the potential for differences in risks of serious adverse events and therapeutic effectiveness, bevacizumab confers considerably greater value than ranibizumab for the treatment of neovascular macular degeneration.

Figure 3. The Impact of the Cost per Ranibizumab Injection and the Risk of Serious Vascular Events Associated with Intravitreal Ranibizumab Use on the Preference for Therapy for Neovascular Age-Related Macular Degeneration

Two-way sensitivity analysis varying the cost of each injection of ranibizumab and risk of serious vascular thrombotic events associated with ranibizumab on which is the preferred treatment option. The color reflects the treatment alternative which is most cost-effective treatment option given a willingness-to-pay of $100 000/QALY. For example, if the cost of each ranibizumab injection was reduced to $1000 and the relative risk of serious vascular events with ranibizumab were 50% lower than those reported in the CATT trial, as needed ranibizumab would be the preferred treatment alternative. Likewise, if the cost of each ranibizumab injection was reduced to $2000 and the risk of serious vascular thrombotic events was 0%, as-needed bevacizumab would be the preferred treatment alternative. CATT = Comparison of Age-Related Macular Degeneration Treatment Trial QALY = quality-adjusted life year

Figure 4. The Impact of the Cost per Bevacizumab and Ranibizumab Injection on the Preference for Therapy for Neovascular Age-Related Macular Degeneration

Two-way sensitivity analysis varying the cost of each injection of bevacizumab and ranibizumab on which is the preferred treatment option. The color reflects the treatment alternative which is most cost-effective treatment option given a willingness-to-pay of $100 000/QALY. For example, if the cost of each ranibizumab injection was reduced to $1500 and the cost of each bevacizumab injection was increased to $600, as needed bevacizumab would be the preferred treatment alternative. Likewise, if the cost of each ranibizumab injection was reduced to $750 and the cost of each bevacizumab injection was increased to $800, as needed ranibizumab would be the preferred treatment alternative. QALY = quality-adjusted life year

Figure 5. The Impact of the Rate of Serious Vascular Thrombotic Events with Bevacizumab and Ranibizumab on the Preference for Therapy for Age-Related Macular Degeneration

Two-way sensitivity analysis demonstrating the impact of varying the rates of serious vascular thrombotic events associated with injections of bevacizumab and ranibizumab on which is the most cost-effective alternative. The color reflects the treatment alternative which is most cost-effective treatment option given a willingness-to-pay of $100 000/QALY. For example, if the rate of serious vascular thrombotic events from ranibizumab injections are 50% lower than those observed in the CATT trial and vascular thrombotic event rates with bevacizumab are 3 times higher than those in the CATT trial, as needed ranibizumab would be the preferred treatment alternative. Likewise, if the rate of serious vascular thrombotic events from ranibizumab injections are 25% lower than those observed in the CATT trial and vascular thrombotic event rates with bevacizumab are 2 times higher than those in the CATT trial, as needed injections of bevacizumab would still be the preferred treatment alternative. Rates reflected in the figure are multiples of the rates of all vascular events (VTE, CVA, and MI) as observed in the CATT trial. Note different scales on the X and Y axes. CATT = Comparison of Age-Related Macular Degeneration Treatment Trial; VTE = venous thrombotic events; CVA = cerebrovascular disease; MI = myocardial infarction; QALY = quality-adjusted life year

Figure 6. The Impact of the Risk of Endophthalmitis with Bevacizumab on the Cost-Effectiveness of Ranibizumab Therapy for Neovascular Age-Related Macular Degeneration

This figure shows the impact of varying the risk of endophthalmitis associated with bevacizumab use from the rates that were reported in the CATT Trial. As the risk of endophthalmitis increases with bevacizumab, the monthly strategy becomes less favorable because it has higher baseline risks of endophthalmitis relative to the as-needed dosing. The ranibizumab strategies become more favorable, but even if the risk of endophthalmitis is 10 times higher with bevacizumab than the risk reported in the CATT Trial, the ranibizumab therapies would have very high cost-effectiveness ratios: as-needed ranibizumab would cost $450 000/QALY and monthly ranibizumab cost over $2.5 million/QALY. CATT = Comparison of Age-Related Macular Degeneration Treatment Trial; QALY = quality-adjusted life years

Figure 10. Probability that Bevacizumab and Ranibizumab Therapy for Neovascular Age-Related Macular Degeneration Will be Cost-Effective Given Uncertainty in All Parameters

Cost-effectiveness acceptability curves derived from 10 000 iterations of Monte Carlo simulations simultaneously varying all model parameters. Note that the x-axis goes up to $1 million per QALY. Bevacizumab strategies are most likely to be cost-effective at willingness-to-pay values of less than $600 000/QALY. Ranibizumab therapies (more likely, as needed ranibizumab) however, are about 14% likely to be cost-effective at a willingness-to-pay of $0/QALY, about 17% likely to be cost-effective at a willingness-to-pay of $100 000/QALY, and about 50% likely to be cost-effective at a willingness-to-pay of $1 million/QALY. Bevacizumab as needed therapy is highly likely to be cost-effective, although there still is a reasonable chance (15–30%) that monthly bevacizumab therapy would be considered cost-effective at all willingness-to-pay levels. QALY = quality-adjusted life year