The Impact of International Pricing Index Models on Anti-Vascular Endothelial Growth Factor (VEGF) Drug Costs in the United States.

OBJECTIVE: To evaluate the impact of three international pricing index models on Medicare Part B spending for intravitreal anti-vascular endothelial growth factor (VEGF) drugs Design: Cost analysis Methods: U.S. and international sales data from the Multinational Integrated Data Analysis (MIDAS) database was used with data from the U.S. Centers for Medicare and Medicaid Services (CMS) to calculate Medicare Part B spending on anti-VEGF drugs Main Outcome: Medicare Part B expenditures of anti-VEGF drugs under various international pricing index models Results: Total Medicare Part B savings was greatest (75%) under the "most favored nation" proposal to peg the U.S. price to the lowest international price. Under the "most favored nation" proposal, prices of aflibercept are reduced from $1825.80 to $507.17, bevacizumab from $74.39 to $27.55, and ranibizumab (3 units or 0.3mg) from $1057.08 to $99.72. CONCLUSION: International pricing index models are one of many pricing strategies that could lead to savings in Medicare Part B costs.

Brolucizumab vs aflibercept and ranibizumab for neovascular age-related macular degeneration: a cost-effectiveness analysis.

BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blindness worldwide and is the most common cause of blindness in developed countries. Despite antivascular endothelial growth factor (anti-VEGF) therapy demonstrating improvements in visual and anatomical outcomes, unmet needs remain. Brolucizumab-dbll (ie, brolucizumab), a VEGF inhibitor for treatment of neovascular (wet) AMD and recently approved by the FDA for its treatment of wet AMD, attempts to mitigate treatment burden through less frequent injections. OBJECTIVE: To assess the incremental cost-effectiveness of brolucizumab compared with aflibercept and ranibizumab, given similar costs per injection and the potential for longer dosing intervals based on phase 3 clinical trial data. METHODS: A Markov model was developed to model the treatment of wet AMD patients with brolucizumab vs aflibercept and vs ranibizumab over a lifetime time horizon (base case) and 5-year time horizon (scenario analysis). The Markov model consisted of 3 primary health states: on treatment, off treatment, and death. Markov substates (5 total) described visual acuity (VA) ranging from no vision impairment to blindness. These VA-based substates were defined by best-corrected visual acuity (BCVA) values measured using Early Treatment Diabetic Retinopathy Study letters. Fixed-dosing regimens for each therapy were included in the model: dosing every 4 weeks (q4w) for the first 3 months followed by dosing q8w/q12w for brolucizumab, dosing q4w for the first 3 months followed by dosing q8w for aflibercept, and q4w for ranibizumab. RESULTS: In the base case, brolucizumab was less costly than aflibercept ($63,614 vs $72,189), and brolucizumab generated 0.0079 more quality-adjusted life-years (QALYs) than aflibercept (4.580 vs 4.572). Lower total costs with brolucizumab were driven by reduced drug costs ($56,432 vs $64,057), reduced administration costs ($6,013 vs $6,825), and reduced monitoring costs ($1,168 vs $1,306). When evaluating the cost-effectiveness of brolucizumab over a 5-year time horizon, brolucizumab was less costly than aflibercept ($44,644 vs $50,772) and generated an additional 0.0049 QALYs (2.953 vs 2.948). Additionally, brolucizumab was less costly than ranibizumab ($63,614 vs $128,163) and generated 0.0078 more QALYs than ranibizumab (4.580 vs 4.572) in the base case. Lower total costs with brolucizumab were driven by reduced drug costs ($56,432 vs $114,516), reduced administration costs ($6,013 vs $11,541), and reduced monitoring costs ($1,168 vs $2,107). When evaluating the cost-effectiveness of brolucizumab over a 5-year time horizon, brolucizumab was less costly than ranibizumab ($44,644 vs $89,665), and brolucizumab generated an additional 0.0046 QALYs (2.953 vs 2.948). CONCLUSIONS: Brolucizumab can be cost saving and cost-effective compared with aflibercept and ranibizumab in the treatment of wet AMD. DISCLOSURES: Novartis Pharmaceuticals Corporation provided funding to Xcenda for the cost-effectiveness analysis and preparation of this manuscript. Carlton is an employee of Xcenda. Agashivala is employed by Novartis Pharmaceuticals Corporation; Yu was an employee of Novartis Pharmaceutical Corporation at the time of this study. Hassan reports personal fees from iOPEN, BVI/Visitrec, ArcticDx, Bayer, F. Hoffmann-La Roche Ltd, Broadspot, BMC, Katalyst Surgical, Alcon, Vitreq, Surgicube, personal Ocugenix, Regeneron, Allergan, Oculus Surgical, Novartis, Genentech, and Eyepoint, unrelated to this work. Wykoff reports personal fees from Corcept Therapeutics, DORC, EyePoint, Gyroscope, IVERIC Bio, Merck, Notal Vision, ONL Therapeutics, Oxurion, Palatin, PolyPhotonix, Takeda, Thea Open Innovation; grants from Aerie Pharmaceuticals, Aldeyra, Gemini Therapeutics, Graybug Vision, IONIS Pharmaceutical, LMRI, Mylan, Neurotech Pharmaceuticals, Outlook Pharmaceuticals, Samsung Bioepis, Senju, Taiwan Liposome Company, Xbrane BioPharma, Santen; and grants and personal fees from Adverum, Allergan, Apellis, Chengdu Kanghong Biotechnologies (KHB), Clearside Biomedical, Genentech, Kodiak Sciences, NGM Biopharmaceuticals, Novartis, Opthea, Recens Medical, Regenxbio, Roche, and Regeneron, unrelated to this work. This research was presented as a virtual poster at the AMCP 2020 Annual Meeting, April 2020.

Intravitreal Anti-Vascular Endothelial Growth Factor Cost Savings Achievable with Increased Bevacizumab Reimbursement and Use.

PURPOSE: To model Medicare Part B and patient savings associated with increased bevacizumab payment and use for intravitreal anti-vascular endothelial growth factor (VEGF) therapy. DESIGN: Cost analysis. PARTICIPANTS: Intelligent Research in Sight (IRIS®) Registry data. METHODS: Medicare claims and IRIS® Registry data were used to calculate Medicare Part B expenditures and patient copayments for anti-VEGF agents with increasing reimbursement and use of bevacizumab relative to ranibizumab and aflibercept. MAIN OUTCOME MEASURES: Medicare Part B costs and patient copayments for anti-VEGF agents in the Medicare fee-for-service population. RESULTS: Increasing bevacizumab reimbursement to $125.78, equalizing the dollar margin with aflibercept, would result in Medicare Part B savings of $468 million and patient savings of $119 million with a 10% increase in bevacizumab market share. CONCLUSIONS: Increased use of bevacizumab achievable with increased reimbursement to eliminate the financial disincentive to its use would result in substantial savings for the Medicare Part B program and for patients receiving anti-VEGF intravitreal injections.

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.

Treatment regimens for administration of anti-vascular endothelial growth factor agents for neovascular age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is one of the leading causes of permanent blindness worldwide. The current mainstay of treatment for neovascular AMD (nAMD) is intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents: aflibercept, ranibizumab, and off-label bevacizumab. Injections can be given monthly, every two or three months ('extended-fixed'), or as needed (pro re nata (PRN)). A variant of PRN is 'treat-and-extend' whereby injections are resumed if recurrence is detected and then delivered with increasing intervals. Currently, injection frequency varies among practitioners, which underscores the need to characterize an optimized approach to nAMD management. OBJECTIVES: To investigate the effects of monthly versus non-monthly intravitreous injection of an anti-VEGF agent in people with newly diagnosed nAMD. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, and three trials registers from 2004 to October 2019; checked references; handsearched conference abstracts; and contacted pharmaceutical companies to identify additional studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared different treatment regimens for anti-VEGF agents in people with newly diagnosed nAMD. We considered standard doses only (ranibizumab 0.5 mg, bevacizumab 1.25 mg, aflibercept 2.0 mg, or a combination of these). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods for trial selection, data extraction, and analysis. MAIN RESULTS: We included 15 RCTs. The total number of participants was 7732, ranging from 37 to 2457 in each trial. The trials were conducted worldwide. Of these, six trials exclusively took place in the US, and three included centers from more than one country. Eight trials were at high risk of bias for at least one domain and all trials had at least one domain at unclear risk of bias. Seven trials (3525 participants) compared a PRN regimen with a monthly injection regimen, of which five trials delivered four to eight injections using standard PRN and three delivered nine or 10 injections using a treat-and-extend regimen in the first year. The overall mean change in best-corrected visual acuity (BCVA) at one year was +8.8 letters in the monthly injection group. Compared to the monthly injection, there was moderate-certainty evidence that the mean difference (MD) in BCVA change at one year for the standard PRN subgroup was -1.7 letters (95% confidence interval (CI) -2.8 to -0.6; 4 trials, 2299 participants), favoring monthly injections. There was low-certainty evidence of a similar BCVA change with the treat-and-extend subgroup (0.5 letters, 95% CI -3.1 to 4.2; 3 trials, 1226 participants). Compared to monthly injection, there was low-certainty evidence that fewer participants gained 15 or more lines of vision with standard PRN treatment at one year (risk ratio (RR) 0.87, 95% CI 0.76 to 0.99; 4 trials, 2299 participants) and low-certainty evidence of a similar gain with treat-and-extend versus monthly regimens (RR 1.11, 95% CI 0.91 to 1.36; 3 trials, 1169 participants). The mean change in central retinal thickness was a decrease of -166 µm in the monthly injection group; the MD compared with standard PRN was 21 µm (95% CI 6 to 32; 4 trials, 2215 participants; moderate-certainty evidence) and with treat-and extend was 22 µm (95% CI 37 to -81 µm; 2 trials, 635 participants; low-certainty evidence), in favor of monthly injection. Only one trial (498 participants) measured quality of life and reported no evidence of a difference between regimens, but data could not be extracted (low-certainty evidence). Both PRN regimens (standard and 'treat-and-extend') used fewer injections than monthly regimens (standard PRN: MD -4.6 injections, 95% CI -5.4 to -3.8; 4 trials, 2336 participants; treat-and-extend: -2.4 injections, 95% CI -2.7 to -2.1 injections; moderate-certainty evidence for both comparisons). Two trials provided cost data (1105 participants, trials conducted in the US and the UK). They found that cost differences between regimens were reduced if bevacizumab rather than aflibercept or ranibizumab were used, since bevacizumab was less costly (low-certainty evidence). PRN regimens were associated with a reduced risk of endophthalmitis compared with monthly injections (Peto odds ratio (OR) 0.13, 95% CI 0.04 to 0.46; 6 RCTs, 3175 participants; moderate-certainty evidence). Using data from all trials included in this review, we estimated the risk of endophthalmitis with monthly injections to be 8 in every 1000 people per year. The corresponding risk for people receiving PRN regimens was 1 in every 1000 people per year (95% CI 0 to 4). Three trials (1439 participants) compared an extended-fixed regimen (number of injections reported in only one large trial: 7.5 in one year) with monthly injections. There was moderate-certainty evidence that BCVA at one year was similar for extended-fixed and monthly injections (MD in BCVA change compared to extended-fixed group: -1.3 letters, 95% CI -3.9 to 1.3; RR of gaining 15 letters or more: 0.94, 95% CI 0.80 to 1.10). The change in central retinal thickness was a decrease of 137 µm in the monthly group; the MD with the extended-fixed group was 8 µm (95% CI -11 to 27; low-certainty evidence). The frequency of endophthalmitis was lower in the extended-fixed regimen compared to the monthly group, but this estimate was imprecise (RR 0.19, 95% CI 0.03 to 1.11; low-certainty evidence). If we assumed a risk of 8 cases of endophthalmitis in 1000 people receiving monthly injections over one year, then the corresponding risk with extended-fixed regimen was 2 in 1000 people (95% CI 0 to 9). Other evidence comparing different extended-fixed or PRN regimens yielded inconclusive results. AUTHORS' CONCLUSIONS: We found that, at one year, monthly regimens are probably more effective than PRN regimens using seven or eight injections in the first year, but the difference is small and clinically insignificant. Endophthalmitis is probably more common with monthly injections and differences in costs between regimens are higher if aflibercept or ranibizumab are used compared to bevacizumab. This evidence only applies to settings in which regimens are implemented as described in the trials, whereas undertreatment is likely to be common in real-world settings. There are no data from RCTs on long-term effects of different treatment regimens.

Cost-Minimization Analysis of Ranibizumab Versus Aflibercept for Treating Saudi Patients With Visual Impairment Owing to Age-Related Macular Degeneration or Diabetic Macular Edema.

OBJECTIVE: The standard-of-care treatment for age-related macular degeneration (AMD) and diabetic macular edema (DME) includes inhibiting blood vessel proliferation and reducing macular edema or swelling using anti-vascular endothelial growth factor therapies, such as ranibizumab and aflibercept. To conduct a cost-minimization analysis of ranibizumab and aflibercept for treating Saudi patients with visual impairment owing to AMD or DME. METHODS: Cost minimization was analyzed assuming that ranibizumab and aflibercept have equivalent clinical effectiveness. The third-party payer's perspective was used in several clinical scenarios. The base-case scenario was DME cases followed monthly using a protocol-specific follow-up. In scenario 1, AMD cases followed a treat-and-extend protocol over 2 years. In scenario 2, AMD cases followed the PRN (pro re nata) regimen over 2 years. In scenario 3, DME cases followed the PRN regimen for 1 year only. RESULTS: Aflibercept yielded cost savings of 25.75%, 31.54%, 51.30%, and 9.28% compared with ranibizumab for the base case, scenario 1, scenario 2, and scenario 3, respectively, which supports the premise that aflibercept is more cost saving than ranibizumab. CONCLUSIONS: From the third-party payer perspective, aflibercept is a cost-containment option that provides substantial savings over ranibizumab for treating Saudi patients with AMD or DME.

Cost-effectiveness of Anti-VEGF treatments for age-related macular degeneration: a Brazilian perspective.

PURPOSE: To study the cost-effectiveness of ranibizumab and bevacizumab for the treatment of age-related macular degeneration. METHODS: We used a decision tree model to analyze the cost-effectiveness of ranibizumab and bevacizumab for the treatment of age-related macular degeneration, from the Brazilian Public Health System (SUS) perspective. Ranibizumab and bevacizumab were administered to patients with the same treatment procedure, and the difference in treatment costs was calculated based on the cost of the drugs. Direct costs were estimated using the information provided by the Brazilian SUS. Effectiveness in terms of quality-adjusted life years (QALYs) was calculated based on the utility values for visual impairment. Incremental cost-effectiveness ratio was calculated by comparing both treatments. The analytical horizon was one year. RESULTS: The decision tree analysis showed that the difference in treatment effectiveness was 0.01 QALY. Incremental cost-effectiveness ratio showed that ranibizumab treatment required an incremental annual cost of more than R$ 2 million to generate 1 additional QALY, as compared to bevacizumab. CONCLUSIONS: From the Brazilian SUS perspective, bevacizumab is more cost-effective than ranibizumab for the treatment of neovascular age-related macular degeneration. Its use could allow potential annual savings in health budget.

Real-World Injection Frequency and Cost of Ranibizumab and Aflibercept for the Treatment of Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema.

BACKGROUND: Ranibizumab and aflibercept are FDA-approved treatments for patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Although these agents differ in cost and labeled dosing, it is unclear whether these differences are reflected in clinical practice. OBJECTIVE: To compare the real-world frequency and cost of ranibizumab and aflibercept injections among treatment-naive and previously treated patients with nAMD and DME. METHODS: Claims data from MarketScan Research Databases were retrospectively reviewed to identify treatment-naive patients with nAMD who initiated intravitreal ranibizumab or aflibercept between January 1, 2014, and January 1, 2016, and treatment-naive patients with DME who initiated intravitreal ranibizumab or aflibercept between July 29, 2014, and July 1, 2016. Patients who switched to subsequent-line aflibercept or ranibizumab during the study period were eligible to enter previously treated subgroups. Multivariable regression models were derived to compare the per-patient frequency and cost of injections between ranibizumab- and aflibercept-treated patients with nAMD over 12 months (treatment-naive: n = 1,087 and n = 1,578; previously treated: n = 221 and n = 751) and 24 months (treatment-naive: n = 454 and n = 568; previously treated: n = 93 and n = 284) and in patients with DME over 6 months (treatment-naive: n = 507 and n = 681; previously treated: n = 53 and n = 223) and 12 months (treatment-naive: n = 326 and n = 382; previously treated: n = 24 and n = 122). RESULTS: After adjusting for patient demographics and clinical characteristics, per-patient injection frequency and cost were not significantly different between treatment-naive patients with nAMD who received ranibizumab versus aflibercept over 12 months (5.62 vs. 5.54; P = 0.52, and $11,351 vs. $10,702; P = 0.06, respectively) and 24 months (7.86 vs. 8.37; P = 0.16, and $16,286 vs. $16,666; P = 0.69, respectively). In previously treated patients with nAMD, injection frequency was significantly lower among ranibizumab- versus aflibercept-treated patients over 24 months (7.98 vs. 9.63; P = 0.03), whereas treatment costs were comparable over 12 months ($11,512 vs. $12,050; P = 0.44) and 24 months ($16,303 vs. $19,361; P = 0.13). In treatment-naive patients with DME, ranibizumab was associated with significantly fewer injections and lower costs than aflibercept over 6 months (2.60 vs. 2.92 and $3,379 vs. $5,925, respectively; both P < 0.001) and 12 months (3.33 vs. 3.87 and $4,136 vs. $7,656, respectively; both P < 0.001). Similar cost savings were observed among previously treated patients with DME who received ranibizumab over 6 months ($3,834 vs. $6,775 for aflibercept; P = 0.0001) and 12 months ($4,606 vs. $9,190; P = 0.02), despite nonsignificant differences in injection frequency during follow-up. CONCLUSIONS: Although the frequency and cost of ranibizumab and aflibercept injections were generally comparable among patients treated for nAMD, ranibizumab was associated with estimated per-patient-per-year cost savings of $3,500-$4,500 in those treated for DME. Most patients received fewer injections than any FDA-indicated dosing schedule, suggesting potential undertreatment that may result in suboptimal vision outcomes. DISCLOSURES: Study funding was provided by Genentech, a member of the Roche Group. The sponsor participated in the design of the study; collection, analysis, and interpretation of the data; preparation of the manuscript; and the decision to submit the article for publication. Kiss has been a consultant for and received honoraria from Alcon, Alimera, Allergan, BioMarin, Novartis, and Spark; has been on the advisory board for, a consultant for, received honoraria from, and held stock options in Adverum and Regenxbio; has been a consultant for, received honoraria from, and held stock/stock options in Fortress; has been on the advisory board for, a consultant and investigator for, and received grants and honoraria from Genentech and Regeneron; and has been on the advisory board for, a consultant for, and received grants and honoraria from Optos. Malangone-Monaco, Wilson, Varker, Stetsovsky, and Smith are employees of IBM Watson Health, which received funding from Genentech to undertake this study. Garmo is an employee of Genentech. Data reported in this manuscript were presented in part at the Academy of Managed Care Pharmacy (AMCP) Managed Care and Specialty Pharmacy Annual Meeting; April 23-26, 2018; Boston, MA.

Cost-effectiveness of Anti-VEGF treatments for age-related macular degeneration: a Brazilian perspective / Estudo de custo-efetividade de tratamentos para a degeneração macular relacionada à idade: uma perspectiva brasileira

ABSTRACT Purpose: To study the cost-effectiveness of ranibizumab and bevacizumab for the treatment of age-related macular degeneration. Methods: We used a decision tree model to analyze the cost-effectiveness of ranibizumab and bevacizumab for the treatment of age-related macular degeneration, from the Brazilian Public Health System (SUS) perspective. Ranibizumab and bevacizumab were administered to patients with the same treatment procedure, and the difference in treatment costs was calculated based on the cost of the drugs. Direct costs were estimated using the information provided by the Brazilian SUS. Effectiveness in terms of quality-adjusted life years (QALYs) was calculated based on the utility values for visual impairment. Incremental cost-effectiveness ratio was calculated by comparing both treatments. The analytical horizon was one year. Results: The decision tree analysis showed that the difference in treatment effectiveness was 0.01 QALY. Incremental cost-effectiveness ratio showed that ranibizumab treatment required an incremental annual cost of more than R$ 2 million to generate 1 additional QALY, as compared to bevacizumab. Conclusions: From the Brazilian SUS perspective, bevacizumab is more cost-effective than ranibizumab for the treatment of neovascular age-related macular degeneration. Its use could allow potential annual savings in health budget.

RESUMO Objetivo: Estudar o custo-efetividade do ranibizumabe e bevacizumabe no tratamento da degeneração macular relacionada à idade neovascular. Métodos: Utilizamos um modelo de árvore de decisão para analisar a relação custo-efetividade do ranibizumabe e bevacizumabe no tratamento da degeneração macular relacionada à idade, sob a perspectiva do Sistema Único de Saúde. O ranibizumabe e bevacizumabe foram administrados a pacientes com o mesmo procedimento de tratamento, e a diferença nos custos do tratamernto foi calculada com base no custo dos medicamentos. Os custos diretos foram estimados utilizando as informações fornecidas pelo SUS. A efetividade foi determinada em anos de vida ajustados pela qualidade (QALY) baseados em valores de utilidade em deficiênciavisual. A razãoincremental custo-efetividadefoicalculada comparando os dois tratamentos. O horizonte analítico foi de um ano. Resultados: A análise da árvore de decisão mostrou que a diferença na efetividade do tratamento foi de 0,01 QALY. A razão incremental de custo-efetividade mostrou que o tratamento com ranibizumabe exigiu um custo anual incremental de R$ 2 milhões para gerar um QALY adicional, em comparação ao bevacizumabe. Conclusões: Do ponto de vista do SUS, o bevacizumabe é mais custo-efetivo que o ranibizumabe no tratamento da degeneração macular relacionada à idade neovascular. O seu uso poderia gerar uma grande economia anual para o orçamento em saúde.

Cost-effectiveness of Intravitreal Ranibizumab With Verteporfin Photodynamic Therapy Compared With Ranibizumab Monotherapy for Patients With Polypoidal Choroidal Vasculopathy.

Importance: The EVEREST II trial showed that for patients with polypoidal choroidal vasculopathy (PCV), intravitreal ranibizumab in combination with verteporfin photodynamic therapy improves visual acuity relative to ranibizumab monotherapy. However, whether combination therapy is incrementally cost-effective relative to monotherapy during a lifetime is unclear. Objective: To assess the incremental cost-effectiveness of combination therapy compared with ranibizumab monotherapy in patients with PCV. Design, Setting, and Participants: This model-based, economic evaluation used 2018 unit cost data from a tertiary eye hospital in Singapore, first- and second-year outcomes and resource use data from a multicenter trial across various Asian countries (EVEREST II) to model a hypothetical cohort of patients with symptomatic PCV. Scenario analyses and deterministic and probabilistic sensitivity analyses were performed to examine uncertainty. Data were collected from October 2018 through April 2019 and analyzed from March through October 2019. Interventions: This model used data from the EVEREST II trial, in which all participants were given 0.5 mg of intravitreal ranibizumab once every 4 weeks for the first 3 months. Subsequent administration occurred as needed. For participants receiving combination therapy, standard fluence (50 J/cm3) photodynamic therapy with 6-mg/m2 verteporfin was administered once during the first 3 months and thereafter as needed. Main Outcomes and Measures: Incremental cost per quality-adjusted life-year (QALY) gained for combination therapy relative to monotherapy for patients with PCV. Results: In this model based on a cohort of 1000 patients aged 68 years, a patient with PCV incurred a total cost in Singapore dollars (SGD) of 92 327 (US $67 399) with combination therapy and SGD 92 371 (US $67 431) with monotherapy during a lifetime horizon, generating a modest cost savings of SGD 44 (US $32) per patient undergoing combination therapy. Lifetime QALYs were estimated to be 7.87 for combination therapy and 7.85 for monotherapy, for an incremental gain of 0.02 QALYs. Combination therapy remained cost-saving or cost-effective in all lifetime scenarios modeled, but during shorter time horizons and at lower monotherapy costs, it may not be cost-effective. Conclusions and Relevance: This study found combination therapy to be a dominant (more effective and less costly) strategy, being similar in costs and slightly more effective than ranibizumab monotherapy during a lifetime horizon. However, decreasing the time horizon to less than 10 years and/or reductions in the cost of monotherapy may result in combination therapy no longer being cost-effective.

Cost-effectiveness of ranibizumab and aflibercept to treat diabetic macular edema from a US perspective: analysis of 2-year Protocol T data.

Aims: Protocol T (NCT01627249) was a head-to-head study conducted by the Diabetic Retinopathy Clinical Research Network that compared intravitreal aflibercept, bevacizumab, and ranibizumab for the treatment of diabetic macular edema (DME). A cost-effectiveness analysis accompanying the 1-year data of Protocol T revealed that aflibercept was not cost-effective vs ranibizumab for all patients, but could have been cost-effective in certain patient sub-groups if the 1-year results were extrapolated out to 10 years. The present study evaluated the cost-effectiveness of US Food and Drug Administration-approved anti-vascular endothelial growth factor agents (ranibizumab, aflibercept) for treatment of DME using the 2-year data from Protocol T.Methods: Costs of aflibercept 2.0 mg or ranibizumab 0.3 mg, visual acuity (VA)-related medical costs, and quality-adjusted life-years (QALYs) were simulated for eight VA health states. Treatment, adverse event management, and VA-related healthcare resource costs (2016 US dollars) were based on Medicare reimbursement and published literature. VA-related health utilities were determined using a published algorithm. Patients were stratified by baseline VA: 20/40 or better; 20/50 or worse.Results: Total 2-year costs were higher, and QALYs similar, for aflibercept vs ranibizumab in the full cohort ($44,423 vs $34,529; 1.476 vs 1.466), 20/40 or better VA sub-group ($40,854 vs $31,897; 1.517 vs 1.519), and 20/50 or worse VA sub-group ($48,214 vs $37,246; 1.433 vs 1.412), respectively. Incremental cost-effectiveness ratios in the full cohort and 20/50 or worse VA sub-group were $986,159/QALY and $523,377/QALY, respectively. These decreased to $711,301 and $246,978 when analyses were extrapolated to 10 years.Limitations: Key potential limitations include the fact that VA was the only QALY parameter analyzed and the uncertainty surrounding the role of better- and worse-seeing eye VA in overall functional impairment.Conclusions: This analysis suggests that aflibercept is not cost-effective vs ranibizumab for patients with DME, regardless of baseline vision.

Real-World Effectiveness and Real-World Cost-Effectiveness of Intravitreal Aflibercept and Intravitreal Ranibizumab in Neovascular Age-Related Macular Degeneration: Systematic Review and Meta-Analysis of Real-World Studies.

INTRODUCTION: Treatment of neovascular age-related macular degeneration (nAMD) has evolved with the advent of anti-vascular endothelial growth factor agents such that intravitreally administered aflibercept and ranibizumab (RBZ) have become the standard of care. Randomized clinical trials (RCTs) have demonstrated the benefits of these agents in nAMD; however, results achieved under RCT protocols may not always be replicated in clinical practice. Assessing real-world outcomes is important to estimate the effectiveness and cost-effectiveness of these two agents. Our objective was to assess the real-world effectiveness of intravitreally administered aflibercept and RBZ in treatment-naive patients with nAMD and determine the cost-effectiveness of intravitreally administered aflibercept versus RBZ in a real-world setting. METHODS: A multistage approach was undertaken. A systematic literature review (SLR) was completed to identify studies describing real-world outcomes in patients with nAMD treated intravitreally with aflibercept or RBZ. A meta-analysis of data identified in the SLR generated a pooled estimate of the effectiveness of intravitreally administered aflibercept and RBZ at 52 weeks and an estimate of treatment burden (injection frequency and monitoring). The impact of treatment effect modifiers, such as baseline visual acuity (VA) and age, were corrected through a multivariable meta-regression. A Markov state transition model was developed to estimate the real-world cost-effectiveness of intravitreally administered aflibercept using results from the pooled estimates for effectiveness and treatment burden as primary inputs. The analysis considered the perspective of the French National Healthcare System. RESULTS: Patients treated intravitreally with aflibercept had a mean age of 79.52 years and mean baseline VA of 55.80 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. At week 52, mean VA gain was 5.30 ETDRS letters in patients reporting an average of 7.10 intravitreal injections of aflibercept and 8.65 visits (injection and/or monitoring). RBZ-treated patients were younger (77.28 years), with a lower mean baseline VA (52.81 ETDRS letters). At week 52, mean VA gain from baseline was 4.24 ETDRS letters, with an average of 5.88 injections and 10.10 visits (injection and/or monitoring). After correcting for differences in age (77.28 years) and baseline VA (52.81 ETDRS letters) and considering the current clinical practice with aflibercept and RBZ, the mean VA gain was 6.57 ETDRS letters for patients treated intravitreally with aflibercept and 4.42 ETDRS for patients treated intravitreally with RBZ. The cost-effectiveness analysis showed that intravitreally administered aflibercept is a more effective treatment option with an incremental gain in quality-adjusted life years (QALYs) (4.918 versus 4.880) and an incremental cost-effectiveness ratio (ICER) of €27,087 per QALY. CONCLUSIONS: The analysis identified differences in the overall treatment approach and how ophthalmologists use intravitreally administered aflibercept and RBZ in clinical practice. These differences ultimately influence the mean real-world effectiveness of the two agents. Intravitreal treatment with aflibercept (injection frequency and patients follow-up) was consistent and in line with the European label recommendations. Patients treated intravitreally with aflibercept in clinical practice reported a mean gain in VA of similar magnitude to the mean VA gain reported in the pivotal RCT. Conversely, treatment with RBZ varied significantly across the different studies. On average, RBZ-treated patients reported a low injection frequency and a frequent follow-up, driven in part by the high number of patients treated with pro re nata (PRN) regimens. RBZ-treated patients reported gains in VA versus baseline; however, the magnitude of the gain in VA was not comparable to the VA gains reported in the RBZ pivotal RCT. Intravitreal treatment with aflibercept was associated with better mean VA outcomes and an incremental gain in QALYs compared with RBZ and can be considered cost-effective for the treatment of nAMD in patients in France despite a higher price for each individual intravitreal injection of aflibercept compared with RBZ. FUNDING: Bayer AG, Basel.

Five-Year Cost-effectiveness of Intravitreous Ranibizumab Therapy vs Panretinal Photocoagulation for Treating Proliferative Diabetic Retinopathy: A Secondary Analysis of a Randomized Clinical Trial.

Importance: The DRCR Retina Network Protocol S randomized clinical trial suggested that the mean visual acuity of eyes with proliferative diabetic retinopathy (PDR) treated with ranibizumab is not worse at 5 years than that of eyes treated with panretinal photocoagulation (PRP). Moreover, the ranibizumab group had fewer new cases of diabetic macular edema (DME) with vision loss or vitrectomy but had 4 times the number of injections and 3 times the number of visits. Although 2-year cost-effectiveness results of Protocol S were previously identified, incorporating 5-year data from Protocol S could alter the longer-term cost-effectiveness of the treatment strategies from the perspective of the health care system. Objective: To evaluate 5- and 10-year cost-effectiveness of therapy with ranibizumab, 0.5 mg, compared with PRP for treating PDR. Design, Setting, and Participants: A preplanned secondary analysis of the Protocol S randomized clinical trial using efficacy, safety, and resource utilization data through 5 years of follow-up for 213 adults diagnosed with PDR and simulating results through 10 years. Interventions: Intravitreous ranibizumab, 0.5 mg, at baseline and as frequently as every 4 weeks based on a structured retreatment protocol vs PRP at baseline for PDR; eyes in both groups could receive ranibizumab for concomitant DME with vision loss. Main Outcomes and Measures: Incremental cost-effectiveness ratios (ICERs) of ranibizumab therapy compared with PRP were evaluated for those with and without center-involved DME (CI-DME) and vision loss (Snellen equivalent, 20/32 or worse) at baseline. Results: The study included 213 adults with a mean (SD) age of 53 (12) years, of whom 92 (43%) were women and 155 (73%) were white. The ICER of the ranibizumab group compared with PRP for patients without CI-DME at baseline was $582 268 per quality-adjusted life-year (QALY) at 5 years and $742 202/QALY at 10 years. For patients with baseline CI-DME, ICERs were $65 576/QALY at 5 years and $63 930/QALY at 10 years. Conclusions and Relevance: This study suggests that during 5 to 10 years of treatment, ranibizumab, 0.5 mg, as given in the studied trial compared with PRP may be within the frequently cited range considered cost-effective in the United States for eyes presenting with PDR and vision-impairing CI-DME, but not for those with PDR but without vision-impairing CI-DME. Substantial reductions in anti-vascular endothelial growth factor cost may make the ranibizumab therapy cost-effective within this range even for patients without baseline CI-DME. Trial Registration: ClinicalTrials.gov identifier: NCT01489189.

Healthcare resource use and costs of diabetic macular oedema for patients with antivascular endothelial growth factor versus a dexamethasone intravitreal implant in Korea: a population-based study.

OBJECTIVES: To estimate the costs and healthcare resources of patients with diabetic macular oedema (DME) who received intravitreal antivascular endothelial growth factor (anti-VEGF) agents or a dexamethasone intravitreal implant (DEX-implant) in Korea. DESIGN: Retrospective cohort study. SETTING: The Korean National Health Insurance claim data from 1 January 2015 to 30 June 2017 were retrieved from the Health Insurance Review and Assessment Service. PARTICIPANTS: Adult patients with DME who were diagnosed with diabetic retinopathy or DME and received ranibizumab, aflibercept or a DEX-implant in conjunction with intravitreal injection were included. Patients whose primary diagnoses were age-related macular degeneration or retinal vein occlusion were excluded. MAIN OUTCOME MEASURES: Healthcare resource utilisation and costs related to DME in the 12-month postindex period. RESULTS: During the study period, 182 patients and 414 patients were identified in the anti-VEGF and DEX-implant groups, respectively, and there was no significant difference in the demographic characteristics between the two groups. The outpatient eye care-related medical costs were US$3002.33 for the anti-VEGF group vs US$2250.35 for the DEX-implant group (p<0.0001). After adjusting the relevant covariates based on the generalised linear model, the estimated outpatient eye care-related medical costs were 33% higher in the anti-VEGF group than in the DEX-implant group (p<0.0001, 95% CI 22% to 45%). The utilisation pattern of the two groups showed no significant difference except for the number of intravitreal injections, which was higher in the anti-VEGF group (2.69±2.29) than in the DEX-implant group (2.09±1.37, p<0.001). CONCLUSION: The average annual eye-related medical cost of the DEX-implant group was significantly lower than that of the anti-VEGF group during the study period, which was mainly due to decreased utilisation of eye care-related injections. Further long-term studies are needed.

[Budget impact of the incorporation of second-line drug treatment for diabetic macular edema in the Brazilian Unified National Health System from the perspective of the Minas Gerais State Health Department, Brazil]. / Impacto orçamentário da incorporação de medicamentos para tratamento em segunda linha do edema macular diabético no SUS sob a perspectiva da Secretaria de Estado de Saúde de Minas Gerais, Brasil.

The study's objective was to perform budget impact assessment for the incorporation of second-line intravitreal antiangiogenic therapy for diabatic macular edema in the scope of the Brazilian Unified National Health System (SUS) in Minas Gerais state, Brazil, discussing the incorporation's state budget feasibility. The budget impact assessment was performed as a deterministic method according to Ministry of Health guidelines. The study included patients with probable first-line treatment failure in a five-year timeline for all the technologies assessed. The analysis included the drugs bevacizumab (off-label use), ranibizumab, and aflibercept. The populations were calculated both by observed demand and epidemiological estimate. The following sensitivity analyses were performed: a scenario with slower technology diffusion, a scenario with the market entry of biosimilar versions of bevacizumab and ranibizumab, and a scenario disregarding inflation during the period. The incremental budget impacts according to observed and epidemiologically estimated demand, respectively, were BRL 69,493,906.95 to BRL 473,226,278.78 for bevacizumab; BRL 349,319,965.60 to BRL 2,378,732,103.09 for ranibizumab; and BRL 543,867,485.47 to BRL 3,703,524,490.16 for aflibercept. Bevacizumab proved to be the most financially feasible alternative in all the scenarios of estimates and sensitivity analyses. An increment of nearly 3% was estimated, compared to the 2016 budget (observed demand). The study showed that the incorporation is feasible in the SUS, Minas Gerais State, but subject to management priorities. Price discrepancies between products with similar efficacy is intriguing and provides fertile ground for future studies.

Os objetivos foram efetuar a análise do impacto orçamentário para a incorporação de segunda linha terapêutica com terapia antiangiogênica de aplicação intravítrea, para tratamento de edema macular diabético, no âmbito do Sistema Único de Saúde (SUS) em Minas Gerais, Brasil, discutindo sua viabilidade à luz do orçamento do estado. A análise do impacto orçamentário com método determinístico, segundo diretriz do Ministério da Saúde. Foram incluídos os pacientes com provável falha ao tratamento de primeira linha, num horizonte temporal de 5 anos para todas as tecnologias avaliadas. Incluíram-se na análise os medicamentos bevacizumabe (uso off-label), ranibizumabe e aflibercepte. As populações foram calculadas tanto por demanda aferida quanto por estimativa epidemiológica. Como análises de sensibilidade efetuaram-se: cenário com difusão de tecnologia mais lenta; cenário com a entrada de bevacizumabe e ranibizumabe biossimilares no mercado; cenário com a desconsideração da inflação no período. O impacto orçamentário incremental, de acordo com as estimativas de demanda aferida e epidemiológica, respectivamente, foi de R$ 69.493.906,95-R$ 473.226.278,78 para bevacizumabe; R$ 349.319.965,60-R$ 2.378.732.103,09 para ranibizumabe e R$543.867.485,47-R$ 3.703.524.490,16 para aflibercepte. Bevacizumabe foi a alternativa financeiramente mais viável em todos os cenários das estimativas e análises de sensibilidade. Estimou-se incremento próximo a 3%, comparando com o orçamento de 2016 (demanda aferida). Avalia-se que a incorporação é viável dentro do SUS em Minas Gerais, mas sujeita às prioridades da gestão. A discrepância de preços entre produtos de eficácia semelhante é intrigante e tema fértil para estudos futuros.

El objetivo fue efectuar un análisis del impacto presupuestario en la incorporación de una segunda línea terapéutica, con terapia antiangiogénica de aplicación intravítrea, para el tratamiento de edema macular diabético, en el ámbito del Sistema Único de Salud (SUS), en Minas Gerais, Brasil, discutiendo su viabilidad respecto al presupuesto del estado. Se realizó una análisis del impacto presupuestario con un método determinístico, según la directriz del Ministerio de Salud. Se incluyeron pacientes con probable fracaso al tratamiento de primera línea, en un horizonte temporal de 5 años para todas las tecnologías evaluadas. Se incluyeron en el análisis los medicamentos bevacizumab (uso off-label), ranibizumab y aflibercept. Las poblaciones se calcularon tanto por demanda evaluada, como por estimación epidemiológica. A modo de análisis de sensibilidad se planteó un escenario con una difusión de tecnología más lenta, un escenario con la entrada de bevacizumab y ranibizumab biosimilares en el mercado, y un escenario con la desconsideración de la inflación durante el período. El incremento del impacto presupuestario, de acuerdo con las estimativas de demanda evaluada y epidemiológica, respectivamente, fue BRL 69.493.906,95-BRL 473.226.278,78 en el caso del bevacizumab; BRL 349.319.965,60-BRL 2.378.732.103,09 en el de ranibizumab y BRL 543.867.485,47-BRL 3.703.524.490,16 en el aflibercept. El bevacizumab se mostró la alternativa financiera más viable en todos los escenarios de estimaciones y análisis de sensibilidad. Se estimó un incremento cercano al 3%, comparándolo con el presupuesto de 2016 (demanda evaluada). Se considera que la incorporación es viable dentro del SUS en Minas Gerais, pero sujeta a las prioridades de la gestión. La discrepancia de precios entre productos de eficacia semejante es intrigante y un tema fértil para estudios futuros.

Managed care opportunities and approaches to supporting appropriate selection of treatment for sight preservation.

When evaluating the impact of vision-destroying diseases, pharmacologic therapies represent a significant cost to patients, insurance providers, and society. Currently, up to 11 million people in the United States have some form of age-related macular degeneration (AMD), which is one of the leading causes of vision loss in older Americans. Ophthalmologists have administered more than 6 million intravitreal injections of aflibercept, bevacizumab, pegaptanib, and ranibizumab last year. Comprehensive assessment requires managed care administrators and clinicians to understand the direct and indirect costs of vision loss as well as the comparative safety and efficacy profiles for each agent. In AMD, it is critical to understand the established and emerging treatment patterns.

Intravitreal Ranibizumab for the Treatment of Visual Impairment Due to Choroidal Neovascularization Associated with Rare Diseases: Cost-Effectiveness in the UK.

INTRODUCTION: This study sought to determine the cost-effectiveness of intravitreal ranibizumab compared with best supportive care (BSC; considered to be no active treatment) for the treatment of visual impairment due to choroidal neovascularization (CNV) associated with causes other than neovascular age-related macular degeneration (nAMD) and pathologic myopia (PM) in a UK setting. METHODS: An individual patient-level simulation model was developed to estimate the lifetime costs and quality-adjusted life years (QALYs) of ranibizumab vs. BSC. Regression analyses, performed on patient-level data collected within the pivotal phase III MINERVA trial, modelled visual acuity (VA) progression while patients remained on treatment. Patient utilities were modelled as a function of VA in both eyes and resource use estimates were based on trial data or the literature. Costs were evaluated from the perspective of the UK National Health Service and personal social services, with future costs and health outcomes discounted at 3.5% per annum. Sensitivity and scenario analyses were conducted. RESULTS: The incremental cost-effectiveness ratio for intravitreal ranibizumab was £1363 per QALY compared to BSC and was associated with an incremental benefit of 1.06 QALYs and an incremental cost of £1444 per patient. Drug and administration costs of intravitreal ranibizumab were offset by the prevention of the development of blindness and its associated costs, while the increase in benefits was driven by a reduction in mortality risk and an improved health-related quality of life attributed to an improvement in VA. The findings were robust to a range of sensitivity analyses and ranibizumab consistently remained cost-effective at a willingness-to-pay threshold of £20,000-30,000 per QALY gained for all sensitivity analyses. CONCLUSION: Intravitreal ranibizumab is a highly cost-effective intervention for the treatment of CNV due to causes other than nAMD and PM as it delivers substantial QALY gains to patients while making cost savings vs. BSC. FUNDING: Novartis Pharmaceuticals UK Ltd.

Comparison of Ophthalmic Medication Prices Between the United States and Australia.

Importance: Health care prices may drive differences in health care costs across high-income nations. Adalimumab, ranibizumab, and aflibercept are high-cost medications in the United States and Australia. A comparison of their prices over time may elucidate how ophthalmic medication prices contribute to health care costs. Objective: To compare changes in the prices of adalimumab, ranibizumab, and aflibercept in the United States and Australia, the highest and lowest spenders on health care, respectively, among high-income nations. Design, Setting, and Participants: This retrospective price comparison study examined prices paid by government entities in the United States (Medicare) and Australia (Pharmaceuticals and Benefits Scheme). The analysis and data collection were conducted from March 28 to May 4, 2018, in accordance with guidelines set by the International Society for Pharmacoeconomics and Outcomes Research Task Force on Good Research Practices and prior published studies. No human participants or related data were included in this study. Exposures: The change in mean prices of adalimumab, ranibizumab, and aflibercept in the United States and Australia. Main Outcomes and Measures: Initial, final, and change in medication price annually from 2013 to 2017 in inflation-adjusted 2017 US dollars. Results: The mean prices (US dollar prices unadjusted for inflation) in 2013 and 2017 in the United States were $1114 ($1053) and $1818 ($1818), respectively, for adalimumab; $2102 ($1988) and $1904 ($1904), respectively, for ranibizumab; and $2074 ($1961) and $1956 ($1956), respectively, for aflibercept. The mean (Australian dollar prices unadjusted for inflation) 2013 and 2017 prices in Australia were $1854 (A $1797) and $1206 (A $1574), respectively, for adalimumab; $2157 (A $2090) and $972 (A $1268), respectively, for ranibizumab; and $2030 (A $1967) and $996 (A $1300), respectively, for aflibercept. The estimated annual change in price for adalimumab was +12.8% (95% CI, 9.1%-16.5%) in the United States compared with -11.1% (95% CI, -15.0% to -7.1%) in Australia, a difference of 23.9% per year (95% CI, 19.7%-28.0%; P < .001). The annual change in price for ranibizumab was -2.6% (95% CI, -3.9% to -1.3%) in the United States compared with -18.5% (95% CI, -29.3% to -7.8%) in Australia, a difference of 15.9% per year (95% CI, 7.6%-24.2%; P = .003). The annual change in price for aflibercept was -1.5% (95% CI, -2.2% to -0.7%) in the United States compared with -16.9% (95% CI, -25.1% to -8.6%) in Australia, a difference of 15.4% (95% CI, 9.1%-21.8%; P = .001). Conclusions and Relevance: Results of this study indicate that the prices of adalimumab, ranibizumab, and aflibercept significantly decreased during the past 5 years in Australia compared with the United States. These data do not indicate why these differences are noted or what actions might affect future pricing in either country.

The impact of anti-vascular endothelial growth factor agents on visual impairment/blindness prevention in patients with diabetic macular edema and on associated patient and caregiver burden in Japan.

AIMS: To estimate the impact of anti-vascular endothelial growth factor (VEGF) agents on visual impairment and blindness avoided in patients with diabetic macular edema (DME) and on associated patient and caregiver productivity loss in Japan. METHODS: This study compared the impact of current care (estimated at 53.8% utilization of anti-VEGF agents using current data) with that of hypothetical care (characterized by a higher utilization of anti-VEGF agents [80.0%], as estimated by an expert panel) of DME patients. A population-based Markov model (two-eye approach) simulated visual acuity (Early Treatment Diabetic Retinopathy Study [ETDRS] letters) transitions over 5 years with DME treatments (intravitreal aflibercept, ranibizumab, and triamcinolone acetonide, and grid/focal laser) in patients with DME. Patient and caregiver productivity loss was determined using the human capital method. RESULTS: In total, 570,000 DME patients were included in the model over 5 years. Increased utilization of anti-VEGF agents resulted in 6,659 fewer cases of severe visual impairment (SVI; 26-35 ETDRS letters) or blindness (0-25 ETDRS letters) compared with the current care approach (26,023 vs 32,682 cases; 20.38% reduction) over this period. Increased utilization of anti-VEGF agents also contributed to productivity loss savings of ¥12.58 billion (US $115.64 million) (i.e., 17.01%) at the end of year 5. The total overall saving over 5 years was ¥45.83 billion (US $421.27 million) (13.45%). LIMITATIONS: Few Japanese data were available, and assumptions were made for some inputs. Vision changes dependent on the function of both eyes were not studied. Only intravitreal (not sub-Tenon's) injections of triamcinolone were considered in this model. Direct costs were not considered. CONCLUSIONS: Increased utilization of anti-VEGF agents can reduce SVI and legal blindness in patients with DME in Japan. This would also be associated with substantial savings in patient and caregiver productivity loss.

Using Post-market Utilisation Analysis to Support Medicines Pricing Policy: An Australian Case Study of Aflibercept and Ranibizumab Use.

OBJECTIVES: To describe how post-market utilisation analysis in Australia informs cost-effectiveness assessment and pricing decisions, using aflibercept and ranibizumab as case studies. METHODS: Pharmaceutical claims were used to identify initiators of aflibercept and ranibizumab in the year after aflibercept-listing (December 2012), and ranibizumab initiators in the year before aflibercept listing. The dispensing rates for each cohort were calculated, and their demographic and clinical characteristics compared using Kruskal-Wallis tests. RESULTS: Aflibercept and ranibizumab each accounted for half the age-related macular degeneration market following aflibercept listing. Aflibercept initiators had similar dispensing rates to ranibizumab initiators in the pre- and post-aflibercept era (~ three scripts during the first 90 days, and eight to nine scripts during the following 12 months). All cohorts were similar in terms of their age, sex, residential aged-care status and geographic remoteness, and no differences were observed in their overall co-morbidity scores and history of thromboembolic events. CONCLUSIONS: Contrary to clinical trial protocols, post-market utilisation research for ranibizumab and aflibercept demonstrates equivalent use in practice in terms of dose frequency, and the demographic and clinical characteristics of initiators. This supports Australia's decision to pay the same price for each rather than giving a premium to aflibercept. Many other countries are likely overpaying for aflibercept if their utilization patterns are similar to Australia's, and could benefit from incorporating routine utilisation assessment.