Acceptability curve of the three anti-VEGF treatments.

<p>The acceptability curve shows the probability of a treatment being cost-effective over a range of willingness-to-pay thresholds. The curve shows that bevacizumab is the most likely to be cost-effective until a willingness-to-pay threshold of €407,250 is reached, after which aflibercept is most likely to be cost-effective.</p

Results of meta-analysis.

<p>Results of meta-analysis.</p

The cost-effectiveness of bevacizumab, ranibizumab and aflibercept for the treatment of age-related macular degeneration—A cost-effectiveness analysis from a societal perspective

<div><p>Background</p><p>The discussion on the use of bevacizumab is still ongoing and often doctors are deterred from using bevacizumab due to legal or political issues. Bevacizumab is an effective, safe and inexpensive treatment option for neovascular age-related macular degeneration (AMD), albeit unregistered for the disease. Therefore, in some countries ophthalmologists use the equally effective but expensive drugs ranibizumab and aflibercept. We describe the economic consequences of this dilemma surrounding AMD treatment from a societal perspective.</p><p>Methods</p><p>We modelled cost-effectiveness of treatment with ranibizumab (as-needed), aflibercept (bimonthly) and bevacizumab (as-needed). Effectiveness was estimated by systematic review and meta-analysis. The drug with the most favourable cost-effectiveness profile compared to bevacizumab was used for threshold analyses. First, we determined how much we overspend per injection. Second, we calculated the required effectiveness to justify the current price and the reasonable price for a drug leading to optimal vision. Finally, we estimated how much Europe overspends if bevacizumab is not first choice.</p><p>Results</p><p>Bevacizumab treatment costs €27,087 per year, about €4,000 less than aflibercept and €6,000 less than ranibizumab. With similar effectiveness for all drugs as shown by meta-analysis, bevacizumab was the most cost-effective. Aflibercept was chosen for threshold analyses. Aflibercept costs €943 per injection, but we determined that the maximum price to be cost-effective is €533. Alternatively, at its current price, aflibercept should yield about twice the visual gain. Even when optimal vision can be achieved, the maximum price for any treatment is €37,453 per year. Most importantly, Europe overspends €335 million yearly on AMD treatment when choosing aflibercept over bevacizumab.</p><p>Conclusion</p><p>Bevacizumab is the most cost-effective treatment for AMD, yet is not the standard of care across Europe. The registered drugs ranibizumab and aflibercept lead to large overspending without additional health benefits. Health authorities should consider taking steps to implement bevacizumab into clinical practice as first choice.</p></div

Utility value per visual acuity category.

<p>Utility value per visual acuity category.</p

Differences in effectiveness and costs between treatments, per patient in the first year of treatment.

<p>The ICERs show that we pay €278,099 per QALY if we use aflibercept instead of bevacizumab and that ranibizumab is dominated by bevacizumab, meaning it is costlier, but does not yield health benefit.</p

Characteristics of early-onset Stargardt cohorts from Radboud university medical center (Radboudumc) and Moorfields Eye Hospital (MEH).

<p>Characteristics of early-onset Stargardt cohorts from Radboud university medical center (Radboudumc) and Moorfields Eye Hospital (MEH).</p

<i>ABCA4</i> variants in early-onset Stargardt patients from Radboud university medical center (Radboudumc) and Moorfields Eye Hospital (MEH).

<p><i>ABCA4</i> variants in early-onset Stargardt patients from Radboud university medical center (Radboudumc) and Moorfields Eye Hospital (MEH).</p

Schematic and representative images of measurements in fundus autofluorescence imaging and spectral-domain optical coherence tomography.

<p>Patient 9: area of questionably decreased autofluorescence (QDAF, blue), 1.37 mm²; area of definitely decreased autofluorescence (black), 0.33 mm²; transverse loss of external limiting membrane (ELM-loss, red), 1.75 mm, transverse loss of ellipsoid zone (EZ-loss, blue), 2.24 mm; best-corrected visual acuity, 20/100; <i>ABCA4</i> variants, c.1622T>C;3113C>T:p.[Leu541Pro;Ala1038Val] and c.6316C>T:p.(Arg2106Cys).</p

Yearly progression rate of changes in retinal eccentricity (<i>ε</i>) by visual function, fundus autofluorescence and optical coherence tomography.

<p>Yearly progression rate of changes in retinal eccentricity (<i>ε</i>) by visual function, fundus autofluorescence and optical coherence tomography.</p

Visual acuity as a function of degrees of retinal eccentricity.

<p>Visual acuity as a function of degrees of retinal eccentricity.</p