Value of Anti-Vascular Endothelial Growth Factor Gene Therapy for Neovascular Age-Related Macular Degeneration.

PURPOSE: To use discounted cash flow (DCF) analysis to estimate the value creation associated with anti-vascular endothelial growth factor (VEGF) genetic therapy for neovascular age-related macular degeneration (nAMD). DESIGN: Economic analysis. PARTICIPANTS: Adults undergoing serial intravitreal anti-VEGF injections in 1 eye for nAMD. METHODS: Discounted cash flow modeling with scenario analysis was used to derive a present value for a 1-time alternative treatment to lifelong anti-VEGF treatment for nAMD. Multiple sensitivity analyses were performed on the basis of patient age at time of first injection and frequency interval of intravitreal injection. MAIN OUTCOME MEASURES: Present values of DCF and scenario analyses. RESULTS: Discounted cash flow analysis of intravitreal anti-VEGF treatment for nAMD resulted in a base-case valuation of $208 420.61, $219 093.31, and $17 379.41 for a 1-time alternative treatment to aflibercept, ranibizumab, and bevacizumab, respectively. This figure covaried significantly with anti-VEGF agent according to the patient age at first injection ($78 323.19-$292 449.87) and frequency of injections ($148 422.91-$388 096.81). In addition, for bevacizumab, variability was driven by the hypothetical degree of clinical superiority of 1-time therapy to repeated intravitreal injections due to reduction in adverse events ($17 379.41-$18 250.79) or reduction in direct or indirect costs associated with age-related macular degeneration ($17 379.41-$657 406.55). CONCLUSIONS: Anti-VEGF gene therapy approaches can create significantly different value propositions based on the agent modeled, patient age at first injection, frequency of injections, and clinical profile of the medication. Although the use of aflibercept or ranibizumab as a comparative cost metric is logical from a bioequivalence perspective, the disparity in medication costs should not be the primary value driver in applied models. Instead, bevacizumab should be the base case ($17 379.41), with additional value driven from an improvement in quality of life through clinical superiority. A reduction in direct and indirect costs can be used to approximate the value from maintained visual acuity, which is elaborated in the DCF analysis approach described in this article. This model can serve as a basis for assessing the price ceiling of myriad gene therapy approaches. Given the high present values for these therapeutics, innovative costing and reimbursement mechanisms should be further explored, with contingencies for sustained efficacy.

A Cost-Benefit Analysis of VEGF-Inhibitor Therapy for Neovascular Age-Related Macular Degeneration in the United States.

PURPOSE: To perform a societal cost-benefit analysis comparing intravitreal bevacizumab (Avastin), ranibizumab (Lucentis), and aflibercept (Eylea) monotherapies for treating neovascular age-related macular degeneration (NVAMD). DESIGN: Cost-benefit analysis. METHODS: Center for Value-Based Medicine using published clinical trial and Medicare data. PATIENT POPULATION: 168,400 estimated 2018 U.S. patients with new-onset NVAMD. Procedure(s): cost-benefit analysis using 2018 U.S. real dollars. OUTCOME MEASUREMENTS: 11-year direct ophthalmic medical costs expended for bevacizumab, ranibizumab, and aflibercept monotherapies were compared with ophthalmic and nonophthalmic direct medical, direct nonmedical, and indirect medical (productivity) costs saved by the therapies. RESULTS: Bevacizumab monotherapy had an individual, 11-year $14,772 treatment cost and net $357,680 societal return (11-year 2,421% return on investment [ROI]). Ranibizumab therapy cost $106,582 and returned $265,870 to society (249% ROI), whereas aflibercept treatment cost $61,811 and returned $310,611 to society (503% ROI). The 2018 NVAMD overall treatment cohort, 11-year net societal gain was $28.5 billion to patients and insurers, with $24.2 billion (84.9%) coming from bevacizumab therapy, $0.7 billion (2.5%) from ranibizumab therapy, and $3.6 billion (12.6%) from aflibercept therapy. Substituting bevacizumab for ranibizumab and aflibercept in the 2018 new-onset NVAMD patients would save an estimated $1.343 billion over 11 years. Vascular endothelial growth factor-inhibitor (VEGF-I) therapy in 2018 should contribute $12.2 billion to the Gross Domestic Product over 11 years. Late treatment would decrease this by 78% to $2.7 billion. CONCLUSIONS: Intravitreal NVAMD bevacizumab, ranibizumab and aflibercept monotherapies accrue considerable financial, ROIs to patients and insurers as they increase national wealth.

Eliminating Visual Acuity and Dilated Fundus Examinations Improves Cost Efficiency of Performing Optical Coherence Tomogrpahy-Guided Intravitreal Injections.

PURPOSE: The clinic efficiency and cost savings achieved by eliminating formal visual acuity (VA) and dilated fundus examinations (DFEs) were assessed for established patients receiving optical coherence tomography (OCT)-guided intravitreal injections. DESIGN: Comparative cost analysis. METHODS: Two different treatment models were evaluated. The first model included patients undergoing routine VA assessment, DFEs, OCT imaging, and intravitreal injections. The second model eliminated the routine VA assessment and DFE while using OCT imaging through an undilated pupil followed by the intravitreal injection. The 2 models incorporated both bevacizumab and aflibercept. The number of patients per clinic day, the cost per visit, and the daily revenues were compared between the 2 models. RESULTS: Optimized schedules with and without VA assessments and DFEs allowed for 48 and 96 patients to be injected per day, respectively. Excluding drug costs, the cost per encounter for the visits with and without a DFE were $39.33 and $22.63, respectively. Including the drug costs, the costs per encounter for the visits with and without a DFE were $85.55 and $68.85 for bevacizumab and $1787.58 and $17770.88 for aflibercept, respectively. Once the reimbursements for each visit type were included, the clinics that eliminated the VA and DFEs were more cost efficient. CONCLUSION: Eliminating both VA assessments and DFEs for patients undergoing OCT-guided retreatment with intravitreal injections resulted in decreased exposure times between patients and clinic staff, decreased cost per encounter, and increased patient volumes per clinic day, resulting in improved clinic efficiency and safety while seeing more patients in a clinic day.

Cost-Utility Analysis of VEGF Inhibitors for Treating Neovascular Age-Related Macular Degeneration.

PURPOSE: To perform 11- and 2-year health care sector (ophthalmic) and societal cost perspective reference case, cost-utility analyses comparing bevacizumab, ranibizumab, and aflibercept monotherapies for neovascular age-related macular degeneration (NVAMD). DESIGN: Cost-utility analysis. METHODS: The authors performed 11-year and 2-year ophthalmic and societal cost perspective, cost-utility analyses comparing bevacizumab, ranibizumab, and aflibercept monotherapies for neovascular age-related macular degeneration (NVAMD). We employed patient utilities, bilateral outcomes, 2018 U.S. dollars, vision-related mortality, a Medicare fee schedule, and CATT (Comparison of Age-Related Macular Degeneration Treatments) study and VIEW (VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD) trial. Cochrane data were also used. SETTING: Center for Value-Based Medicine. Patient/study population: patients with NVAMD. INTERVENTION: Cost-utility analyses using published data. Data-modeled 10-year vision outcomes were modeled forward to year 11. MAIN OUTCOME MEASUREMENT: These included cost-utility ratios (CURs), costs, and quality-adjusted life-years (QALYs) gained. $100,00/QALY was considered the US cost-effectiveness upper limit. RESULTS: Bevacizumab and ranibizumab each conferred an 11-year, 1.339 QALY gain versus observation. Aflibercept conferred a 1.380 QALY gain. Aflibercept conferred greater QALY gain for less cost than ranibizumab but was not cost-effective compared to bevacizumab ($1,151,451/QALY incremental CUR). The average ophthalmic cost perspective CUR for bevacizumab was $11,033/QALY, $79,600/QALY for ranibizumab, and $44,801/QALY for aflibercept. Eleven-year therapies saved a 1.0 year-of-life loss without treatment from the 11.0-year life expectancy. Early treatment was 138%-149% more cost-effective than late treatment. Two-year therapy prevented a 1-month-of-life loss, and revealed bevacizumab, ranibizumab, and aflibercept conferred 0.141, 0.141, and 0.164 QALY gains, respectively, with corresponding average CURs of $40,371/QALY, $335,726/QALY, and $168,006/QALY, respectively. CONCLUSIONS: From an ophthalmic (medical) cost perspective, bevacizumab, ranibizumab, and aflibercept NVAMD monotherapies were all cost-effective over 11 years, with bevacizumab 6.21× more cost-effective than ranibizumab and 3.06× more cost-effective than aflibercept. Two-year modeling revealed bevacizumab was cost-effective, whereas ranibizumab and aflibercept were not. Early treatment was critical for obtaining optimal vision and cost-effectiveness, as is long-term follow-up and adherence to treatment.

Social Cost of Blindness Due to AMD and Diabetic Retinopathy in the United States in 2020.

BACKGROUND AND OBJECTIVE: To estimate the social cost of blindness due to wet age-related macular degeneration (wAMD), diabetic macular edema (DME), and proliferative diabetic retinopathy (PDR) in the United States in 2020. PATIENTS AND METHODS: Excess costs that occur because of blindness were estimated as the difference in costs in blind versus non-blind individuals. Per-patient costs were aggregated using the number of cases of blindness due to wAMD, DME, and PDR projected in 2020. RESULTS: Associated annual excess direct costs, indirect costs, and quality-adjusted life year loss per blind individual were $4,944, $54,614, and 0.214, respectively. Combining estimates with 246,423 projected cases of blindness due to wAMD, DME, and PDR translated to total societal costs of $20 billion in 2020, estimated to triple by 2050. CONCLUSION: Excess social costs associated with blindness in individuals with wAMD, DME, and PDR are substantial, with more than half of the burden attributed to indirect costs. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:S6-S14.].

Economic Value of Anti-Vascular Endothelial Growth Factor Treatment for Patients With Wet Age-Related Macular Degeneration in the United States.

Importance: Anti-vascular endothelial growth factor (anti-VEGF) is a breakthrough treatment for wet age-related macular degeneration (wAMD), the most common cause of blindness in western countries. Anti-VEGF treatment prevents vision loss and has been shown to produce vision gains lasting as long as 5 years. Although this treatment is costly, the benefits associated with vision gains are large. Objective: To estimate the economic value of benefits, costs for patients with wAMD, and societal value in the United States generated from vision improvement associated with anti-VEGF treatment. Design, Setting, and Participants: This economic evaluation study used data from the published literature to simulate vision outcomes for a cohort of 168 820 patients with wAMD aged 65 years or older and to translate them into economic variables. Data were collected and analyzed from March 2018 to November 2018. Main Outcomes and Measures: Main outcomes included patient benefits, costs, and societal value. Each outcome was estimated for a newly diagnosed cohort and the full population across 5 years, with a focus on year 3 as the primary outcome because data beyond that point may be less representative of the general population. Drug costs were the weighted mean across anti-VEGF therapies. Two current treatment scenarios were considered: less frequent injections (mean [SD], 8.2 [1.6] injections annually) and more frequent injections (mean [range], 10.5 [6.8-13.1] injections annually). The 2 treatment innovation scenarios, improved adherence and best case, had the same vision outcomes as the current treatment scenarios had but included more patients treated from higher initiation and lower discontinuation. Results: The study population included 168 820 patients aged 65 years at the time of diagnosis with wAMD. The underlying clinical trials that were used to parameterize the model did not stratify visual acuity outcomes or treatment frequency by sex; therefore, the model parameters could not be stratified by sex. The current treatment scenario of less frequent injections generated $1.1 billion for the full population in year 1 and $5.1 billion in year 3, whereas the scenario of more frequent injections generated $1.6 billion (year 1) and $8.2 billion (year 3). Three-year benefits ranged from $7.3 billion to $11.4 billion in the improved adherence scenario and from $9.7 billion to $15.0 billion if 100% of the patients initiated anti-VEGF treatment and the discontinuation rates were 6% per year or equivalent to clinical trial discontinuation (best-case scenario). Societal value (patient benefits net of treatment cost) ranged from $0.9 billion to $3.0 billion across 3 years in the current treatment scenarios and from $0.9 billion to $4.3 billion in the treatment innovation scenarios. Conclusions and Relevance: This study's findings suggest that improved vision associated with anti-VEGF treatment may provide economic value to patients and society if the outcomes match published outcomes data used in these analyses; however, future innovations that increase treatment utilization may result in added economic benefit.

Socio-economic status and outcomes for patients with age-related macular degeneration.

OBJECTIVES: To explore disparities in severity of baseline disease, treatment completion, and treatment outcomes among patients with wet age-related macular degeneration (AMD) receiving anti-vascular endothelial growth factor therapy by socio-economic status (SES) and distance from home to hospital. STUDY DESIGN: Retrospective cohort study. METHODS: Data from clinic records of 756 wet AMD patients receiving treatment for wet AMD with aflibercept between May 2013 and Jan 2017 were obtained. Area SES (using Index of Multiple Deprivation (IMD) 2015) and distance from hospital (dichotomized > = 10 vs. <10 km) were derived from anonymized postcodes. Univariate and multivariable logistic regression models were used to identify associations of area deprivation and distance from hospital at baseline-with visual acuity (VA) at baseline-treatment completion, and treatment outcome. RESULTS: Living in the most deprived compared with less deprived areas was associated with a significantly higher risk of presenting with severe reduction in VA (OR = 3.59; 95% CI = 1.39-9.27; P = .01). This association was maintained after adjustment for age, gender, and distance from hospital. On univariate analysis, delayed treatment completion was more likely in those living in most deprived areas (OR = 2.80; 95% CI = 1.21-6.47; P = .04), though this association was attenuated after adjustment for age, gender, and distance from hospital. No association was observed between SES and treatment outcomes or between distance from hospital and baseline VA, treatment completion or treatment outcome. CONCLUSION: This study found poorer baseline VA among people with wet AMD from more deprived areas. This work suggests a need for earlier identification of AMD among more deprived populations.

The economic and humanistic burden of patients in receipt of current available therapies for nAMD.

AIM: To determine the economic and humanistic burden of neovascular age-related macular degeneration (nAMD) in a cohort of patients treated with anti-VEGF in Europe and the US. PATIENTS & METHODS: 79 respondents from the EU and 63 from the US with a self-reported diagnosis of nAMD and in current receipt of treatment, as reported in an international, general population survey, were compared with non-nAMD controls. RESULTS: Anti-VEGF-treated nAMD patients in the EU had a greater utilization of healthcare resources, poorer quality of life and greater overall activity impairment versus non-nAMD controls. In the US cohort, treated nAMD patients had significantly greater resource utilization for ophthalmologist visits only. CONCLUSION: The burden of care associated with nAMD on EU and US healthcare systems, and on patients who are in receipt of nAMD therapy, is significant and likely to be unsustainable.

A systematic review on the quality, validity and usefulness of current cost-effectiveness studies for treatments of neovascular age-related macular degeneration.

PURPOSE: Ophthalmologists increasingly depend on new drugs to advance their treatment options. These options are limited by restraints on reimbursements for new and expensive drugs. These restraints are put in place through health policy decisions based on cost-effectiveness analyses (CEA). Cost-effectiveness analyses need to be valid and of good quality to support correct decisions to create new treatment opportunities. In this study, we report the quality, validity and usefulness of CEAs for therapies for nAMD. METHODS: A systematic review in PubMed, EMBASE and Cochrane was performed to include CEAs. Quality and validity assessment was based on current general quality criteria and on elements that are specific to the field of ophthalmology. RESULTS: Forty-eight CEAs were included in the review. Forty-four CEAs did not meet four basic model quality and validity criteria specific to CEAs in the field of ophthalmology (both eyes analysed instead of one; a time horizon extending beyond 4 years; extrapolating VA and treatment intervals beyond trial data realistically; and including the costs of low-vision). Four CEAs aligned with the quality and validity criteria. In two of these CEAs bevacizumab as-needed (PRN) was more cost-effective than bevacizumab monthly; aflibercept (VIEW); or ranibizumab monthly or PRN. In two CEAs, ranibizumab (PRN or treat and extent) was dominant over aflibercept. In two other CEAs, aflibercept was either more cost-effective or dominant over ranibizumab monthly or PRN. CONCLUSION: Two of the CEAs of sufficient quality and validity show that bevacizumab PRN is the most cost-effective treatment. Comparing ranibizumab and aflibercept, either treatment can be more cost-effective depending on the assumptions used for drug prices and treatment frequencies. The majority of the published CEAs are of insufficient quality and validity. They wrongly inform decision-makers at the cost of opportunities for ophthalmologists to treat patients. As such, they may negatively influence overall patient outcomes and societal costs. For future ophthalmic treatments, CEAs need to be improved and only published when they are of sufficient quality and validity.

Intravitreal Aflibercept Versus Ranibizumab for Wet Age-Related Macular Degeneration: A Cost-Effectiveness Analysis.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of vision loss in the United States. The most severe vision loss occurs in patients with neovascular AMD, known as wet AMD (wAMD). The most commonly used antivascular endothelial growth factor (VEGF) therapies approved by the FDA to treat patients with wAMD are ranibizumab, 0.5 mg administered by intravitreal injection once a month (approximately every 28 days), and intravitreal aflibercept injection (IAI), 2 mg every 4 weeks (monthly) for the first 12 weeks (3 months), followed by IAI 2 mg once every 8 weeks (2 months). Given the similar efficacy and safety profiles between IAI and ranibizumab, their associated costs and comparative cost-effectiveness are key factors in determining which one represents a more rational investment of scarce health care resources to help address the increasing cost of prescription drugs in the United States, a source of concern for patients, prescribers, payers, and policymakers. OBJECTIVE: To assess the cost-effectiveness of intravitreal aflibercept injection 2 mg every 8 weeks after 3 initial monthly doses (IAI 2q8) versus ranibizumab 0.5 mg monthly (Rq4) and pro re nata (PRN) in the treatment of patients with wAMD from a U.S. payer perspective. METHODS: A Markov cohort model was developed to estimate the lifetime quality-adjusted life-years (QALYs) and costs of treating patients with wAMD with IAI 2q8, Rq4, and ranibizumab PRN. The model considered changes in best-corrected visual acuity in the affected and fellow eyes over time, and the effect of blindness on mortality. Efficacy for IAI 2q8 and Rq4 was from VIEW 1 and VIEW 2 studies and from the Comparison of AMD Treatments Trials for ranibizumab PRN. Utilities and costs (in 2016 U.S. dollars) were from published literature. Health outcomes and costs were discounted at an annual rate of 3%. RESULTS: Over a lifetime, IAI 2q8 provided equal health benefits with Rq4 (5.44 QALYs) at a lower total cost ($33,745 vs. $48,031) as a result of fewer injections. IAI 2q8 yielded slightly greater QALYs versus ranibizumab PRN (5.44 vs. 5.40) at a slightly higher cost ($33,745 vs. $33,652), with an incremental cost per QALY gained of $2,583. Results were sensitive to variations in drug acquisition costs and number of injections of both drugs and the baseline age of the cohort. CONCLUSIONS: IAI 2q8 can be cost saving and cost-effective compared with Rq4 and ranibizumab PRN for the treatment of wAMD in the United States. DISCLOSURES: This study was funded by Regeneron Pharmaceuticals, the manufacturer of aflibercept. Hernandez, Lanitis, Cele, and Toro-Diaz are employed by Evidera, which received funding from Regeneron Pharmaceuticals to conduct this study. Gibson and Kuznik are employed by and own stock in Regeneron Pharmaceuticals.

Estimating Medicare and Patient Savings From the Use of Bevacizumab for the Treatment of Exudative Age-related Macular Degeneration.

PURPOSE: The Medicare cost savings from the use of bevacizumab in the United States for the treatment of exudative age-related macular degeneration (AMD) were estimated by replacing the use of bevacizumab with ranibizumab and aflibercept. DESIGN: Retrospective trend study. METHODS: Main outcome measures were spending by Medicare as tracked by Current Procedural Terminology (CPT) codes for intravitreal injections (67028) and treatment-specific J-codes (J0178, J2778, J9035, J3490, and J3590) for inhibitors of vascular endothelial growth factor. These claims were identified from the Medicare Provider Utilization and Payment Data from the Centers for Medicare and Medicaid Services among fee-for-service (FFS) Medicare beneficiaries from 2012 to 2015. The 2008 claims were acquired from the 100% fee-for-service (FFS) Part B Medicare Claims File. RESULTS: The use of bevacizumab from 2008 to 2015 resulted in an estimated savings of $17.3 billion, which corresponded to a $13.8 billion savings to Medicare and a $3.5 billion savings to patients. This amount underestimated the actual cost savings to Medicare providers, since approximately 30% of Medicare-eligible recipients received care within Medicare Advantage plans and were not included in this analysis. CONCLUSIONS: The cost savings from the use of bevacizumab from 2008 to 2015 for Medicare fee-for-service patients undergoing treatment for exudative AMD was estimated at $17.3 billion. Additional savings over the $17.3 billion would have accrued from the use of bevacizumab if diagnostic categories such as diabetic macular edema and retinal vein occlusion were included in this study.

Influence of new societal factors on neovascular age-related macular degeneration outcomes.

BACKGROUND: To assess the impact of unstudied societal factors for neovascular age-related macular degeneration (nAMD) on functional outcomes after anti-VEGFs. METHODS: Charts of 94 nAMD patients treated in the Monticelli-Paradis Centre, Marseille, France, were reviewed. Phone interviews were conducted to assess societal factors, including transportation, living status, daily reading and social security scheme (SSS). Primary outcome was the impact of family support and disease burden on functional improvement in nAMD. RESULTS: Between baseline and month 24 (M24), 42.4% of the variability in best-corrected visual acuity (BCVA) was explained by the cumulative effect of the following societal factors: intermittent out-patient follow-up, marital status, daily reading, transportation type, commuting time. No isolated societal factor significantly correlated with ETDRS BCVA severity at M24. A trend to correlation was observed between the EDTRS score at M24 and the SSS (P = 0.076), economic burden (P = 0.075), time between diagnosis and treatment initiation (P = 0.070). A significant correlation was found for the disease burdensome on the patient (P = 0.034) and low vision rehabilitation (P = 0.014). CONCLUSIONS: Societal factors could influence functional outcomes in nAMD patients treated with anti-VEGFs. They could contribute to the healing process or sustain disease progression.

Challenges Associated with Estimating Utility in Wet Age-Related Macular Degeneration: A Novel Regression Analysis to Capture the Bilateral Nature of the Disease.

INTRODUCTION: The estimation of utility values for the economic evaluation of therapies for wet age-related macular degeneration (AMD) is a particular challenge. Previous economic models in wet AMD have been criticized for failing to capture the bilateral nature of wet AMD by modelling visual acuity (VA) and utility values associated with the better-seeing eye only. METHODS: Here we present a de novo regression analysis using generalized estimating equations (GEE) applied to a previous dataset of time trade-off (TTO)-derived utility values from a sample of the UK population that wore contact lenses to simulate visual deterioration in wet AMD. This analysis allows utility values to be estimated as a function of VA in both the better-seeing eye (BSE) and worse-seeing eye (WSE). RESULTS: VAs in both the BSE and WSE were found to be statistically significant (p < 0.05) when regressed separately. When included without an interaction term, only the coefficient for VA in the BSE was significant (p = 0.04), but when an interaction term between VA in the BSE and WSE was included, only the constant term (mean TTO utility value) was significant, potentially a result of the collinearity between the VA of the two eyes. The lack of both formal model fit statistics from the GEE approach and theoretical knowledge to support the superiority of one model over another make it difficult to select the best model. CONCLUSION: Limitations of this analysis arise from the potential influence of collinearity between the VA of both eyes, and the use of contact lenses to reflect VA states to obtain the original dataset. Whilst further research is required to elicit more accurate utility values for wet AMD, this novel regression analysis provides a possible source of utility values to allow future economic models to capture the quality of life impact of changes in VA in both eyes. FUNDING: Novartis Pharmaceuticals UK Limited.

Simulation Modelling in Ophthalmology: Application to Cost Effectiveness of Ranibizumab and Aflibercept for the Treatment of Wet Age-Related Macular Degeneration in the United Kingdom.

BACKGROUND: Previously developed models in ophthalmology have generally used a Markovian structure. There are a number of limitations with this approach, most notably the ability to base patient outcomes on best-corrected visual acuity (BCVA) in both eyes, which may be overcome using a different modelling structure. Simulation modelling allows for this to be modelled more precisely, and therefore may provide more accurate and relevant estimates of the cost effectiveness of ophthalmology interventions. OBJECTIVE: This study aimed to explore the appropriateness of simulation modelling in ophthalmology, using the disease area of wet age-related macular degeneration (wAMD) as an example. METHODS: A de novo economic model was built using a patient-level simulation, which compared ranibizumab with aflibercept in wAMD. Disease progression was measured using BCVA. Health-related quality of life (HRQoL) was estimated using a regression analysis linking BCVA in each eye to utility. The analysis was from the perspective of the National Health Service in the UK. Five different regression models were explored and were based on BCVA in either one eye or both eyes. RESULTS: The model outputs provide some evidence to support the hypothesis that the analyses using the two-eye models for estimating HRQoL generate a more accurate estimation of incremental quality-adjusted life-years (QALYs) associated with the positive treatment effect for ranibizumab versus aflibercept. Second-order analysis broadly supported these findings, and showed that the variation in incremental costs was slightly lower than in incremental QALYs. The second-order analysis estimated similar incremental costs and a greater overall variation in incremental QALYs than the first-order analysis, suggesting important non-linearities within the model. CONCLUSIONS: This analysis suggests that patient-level simulation models may be well suited to representing the real-world patient pathway in wAMD, particularly when aspects of disease progression cannot be adequately captured using a Markov structure. The benefits of a simulation approach can be demonstrated in the modelling of HRQoL as a function of BCVA in both eyes.

[An eye for an eye? Lack of consensus in off-label use of medications leads to major regional differences in medical costs for the treatment of wet AMD in Sweden]. / Öga för öga? - Olika syn på förskrivning ¼off label« ger stora regionala skillnader i behandling vid sjukdom i gula fläcken.

An eye for an eye? Lack of consensus in off-label use of medications leads to major regional differences in medical costs for the treatment of wet AMD in Sweden. The three ocular VEGF inhibitors available in Sweden have similar efficacy and safety. Only two are however registered for wet AMD. The remaining, Avastin, is developed for oncological indications, but used for wet AMD in many parts of the world. Major regional differences exist in the use of Avastin in Sweden. In the three largest cities, it is not used at all. As a consequence, the yearly drug cost for a patient with wet AMD differs from 2 000 to 44 000 SEK. As this difference is not compatible with the Swedish law of "care on equal terms", increased efforts should be made to obtain a national consensus.

Cost-effectiveness of treating wet age-related macular degeneration at the Kuopio University Hospital in Finland based on a two-eye Markov transition model.

PURPOSE: Wet age-related macular degeneration (AMD) is the leading cause of blindness worldwide, which can be treated with regular intraocular anti-vascular endothelial growth factor (VEGF) injections. In this study, we wanted to evaluate whether less frequent injections of aflibercept would make it more cost-effective when compared with ranibizumab and low priced bevacizumab. METHODS: We used a two-eye model to simulate the progression and the treatment of the disease. We selected an 8-year period, 3-month cycles and five health states based on the visual acuity of the better-seeing eye. The transition probabilities and utilities attached to the health states were gathered from previous studies. We conducted the analysis from the hospital perspective and we used the health care costs obtained from Kuopio University Hospital. The costs of intraocular adverse events were taken into account. RESULTS: The incremental cost-effectiveness ratio (ICER) with 3% discount rate (€/QALY) for aflibercept compared with monthly bevacizumab was 1 801 228 and when compared with ranibizumab given as needed, the ICER was minus 3 716 943. The sensitivity analysis showed that a change of 20% of the estimated model parameters or a longer follow-up period did not influence these conclusions. CONCLUSION: A two-eye Markov transition model was developed to analyse the cost-effectiveness of wet AMD treatment, as quality of life years (QALYs) are largely based on the visual acuity of the better-seeing eye. Monthly injected bevacizumab was the most cost-effective treatment and monthly ranibizumab the least effective.

The Cost-Effectiveness of Ranibizumab Treat and Extend Regimen Versus Aflibercept in the UK.

INTRODUCTION: Wet age-related macular degeneration (AMD) is a chronic eye condition that causes severe deterioration of vision and even blindness. Current wet AMD treatment in the UK involves the vascular endothelial growth factor inhibitors ranibizumab and aflibercept. Patients with wet AMD require frequent and long-term monitoring for treatment to be effective, contributing to a substantial resource burden at wet AMD centers. The European license for ranibizumab was recently updated with an individualized 'treat and extend' (T&E) regimen, comprising a structured monitoring and treatment protocol. This study evaluated the cost-effectiveness of ranibizumab T&E versus aflibercept within a UK setting. METHODS: An individual patient-level simulation model was developed utilizing treatment effects from a network meta-analysis of randomized controlled trials. The model was conducted from a UK National Health Service (NHS) perspective over a lifetime horizon and the base case utilized probabilistic sensitivity analysis to assess uncertainty in the model. Additional scenario analyses were conducted to assess the impact of changes to the model inputs. RESULTS: Ranibizumab T&E was found to be more effective and less costly than aflibercept, providing, on average, an additional 1.058 quality-adjusted life years (QALYs) and a cost-saving of £19,604 over a lifetime horizon. At list price, ranibizumab T&E was found to be cost-effective versus aflibercept in 100% of simulations at a willingness-to-pay threshold of £20,000 per QALY. The robustness of the results was tested in several scenario analyses; ranibizumab T&E was found to be more effective, and less costly, than aflibercept in the vast majority of cases. CONCLUSION: This evaluation suggests that treating patients with ranibizumab according to the T&E regimen could be a better use of NHS resources than aflibercept, and could, therefore, be considered as a first-line regimen for patients with wet AMD in the UK. FUNDING: Novartis Pharmaceuticals UK Limited.