Cost-Utility Comparison of Bevacizumab and Aflibercept in the Treatment of Central or Hemiretinal Vein Occlusion in the SCORE2 Trial.

Importance: Retinal vein occlusion is the second most common retinal vascular disease. Bevacizumab was demonstrated in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2) to be noninferior to aflibercept with respect to visual acuity in study participants with macular edema due to central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO) following 6 months of therapy. In this study, the cost-utility of bevacizumab vs aflibercept for treatment of CRVO is evaluated. Objective: To investigate the relative cost-effectiveness of bevacizumab vs aflibercept for treatment of macular edema associated with CRVO or HRVO. Design, Setting, and Participants: This economic evaluation study used a microsimulation cohort of patients with clinical and demographic characteristics similar to those of SCORE2 participants and a Markov process. Parameters were estimated and validated using a split-sample approach of the SCORE2 population. The simulated cohort included 5000 patients who were evaluated 100 times, each with a different set of characteristics randomly selected based on the SCORE2 trial. SCORE2 data were collected from September 2014 October 2019, and data were analyzed from October 2019 to July 2021. Interventions: Bevacizumab (followed by aflibercept among patients with a protocol-defined poor or marginal response to bevacizumab at month 6) vs aflibercept (followed by a dexamethasone implant among patients with a protocol-defined poor or marginal response to aflibercept at month 6). Main Outcomes and Measures: Incremental cost-utility ratio. Results: The simulation demonstrated that patients treated with aflibercept will have an expected cost $18 127 greater than those treated with bevacizumab in the year following initiation. When coupled with the lack of clinical superiority over bevacizumab (ie, patients treated with bevacizumab had a gain over aflibercept in visual acuity letter score of 4 in the treated eye and 2 in the fellow eye), these results demonstrate that first-line treatment with bevacizumab dominated aflibercept in the simulated cohort of SCORE2 participants. At current price levels, aflibercept would be considered the preferred cost-effective option only if treatment restored the patient to nearly perfect health. Conclusions and Relevance: While there will be some patients with CRVO-associated or HRVO-associated macular edema who will benefit from first-line treatment with aflibercept rather than bevacizumab, given the minimal differences in visual acuity outcomes and large cost differences for bevacizumab vs aflibercept, first-line treatment with bevacizumab is cost-effective for this condition.

The Biosimilar Paradox: How Anti-Vascular Endothelial Growth Factor Biosimilars Could Increase Patient and Overall Health Care Costs.

PURPOSE: Anti-vascular endothelial growth factor (VEGF) medications for intraocular use are a major and increasing cost, and biosimilars may be a means of reducing the high cost of many biologic medications. However, a bevacizumab biosimilar, which is currently pending Food and Drug Administration (FDA) approval (bevacizumab-vikg), paradoxically may increase the cost burden of intravitreal anti-VEGF agents, because off-label repackaged drugs may no longer be allowed per the Drug Quality and Security Act (DQSA). We aimed to investigate the potential impact of biosimilars on costs in the United States. DESIGN: Cost analysis of anti-VEGF medications. PARTICIPANTS: Medicare data from October 2022 and previously published market share data from 2019. METHODS: Average sales prices (ASPs) of ranibizumab, aflibercept, and bevacizumab were calculated from Medicare allowable payments. The ASPs of biosimilars were calculated from wholesale acquisition costs from a representative distributor. The cost of an intraocular bevacizumab formulation is modeled at $500/1.25-mg dose and $900/1.25-mg dose. MAIN OUTCOME MEASURES: Costs of anti-VEGF drugs to Medicare Part B and patients. RESULTS: If an intraocular bevacizumab biosimilar were to be priced at $500, costs to Medicare would increase by $457 million from $3.01 billion to $3.47 billion (15.2% increase). Patient responsibility would increase by $117 million from $768 million to $884 million. Similarly, if intraocular bevacizumab were priced at $900, Medicare costs would increase by $897 million to $3.91 billion (29.8% increase), and patient responsibility would increase by $229 million to $997 million. If bevacizumab were $500/dose, switching all patients currently receiving ranibizumab or aflibercept to respective biosimilars would compensate for only 28.8% of the increased cost. Current prices of ranibizumab and aflibercept biosimilars would have to decrease by an aggregate of 15.7% to $616.80/injection, $1027.97/injection, and $1436.88/injection for ranibizumab 0.3 mg, ranibizumab 0.5 mg, and aflibercept, respectively. CONCLUSIONS: An FDA-approved bevacizumab biosimilar for ophthalmic use could increase costs to the health care system and patients, raising concerns for access. This increase would not be offset by ranibizumab and aflibercept biosimilar use at current prices. These data support the need for an exemption of section 503B of the DQSA and continued use of repackaged off-label bevacizumab. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR PHARMACEUTICAL UTILIZATION AND FINANCIAL IMPACT IN A VALUE-BASED CARE PROGRAM.

PURPOSE: To investigate trends and the potential impact of the COVID-19 pandemic on the utilization of intravitreal antivascular endothelial growth factor (anti-VEGF) pharmaceuticals in an accountable care organization (ACO). METHODS: We retrospectively analyzed the Centers for Medicare and Medicaid Services beneficiary claims for all patients in the Houston Methodist Coordinated Care ACO registry during the years 2018, 2019, and 2020. RESULTS: Across the 3 years studied, a mean of 708 patients received anti-VEGF injections per year. The percentage of patients who received anti-VEGF injections decreased in each sequential year, with a steeper decline during the COVID-19 pandemic in the year 2020 (decrease by 0.4% from 2019 to 2020, P < 0.001; decrease by 0.2% from 2018 to 2019, P = 0.1453). The percentage of patients receiving bevacizumab of the total number of patients receiving any anti-VEGF treatment decreased (bevacizumab decreased by 6% from 2019 to 2020, P = 0.0174; decreased by 7% from 2018 to 2019, P = 0.0074). The COVID-19 pandemic did not seem to correlate with a change in the distribution of the specific anti-VEGF injection used. CONCLUSION: Despite the lower price which may correlate with value-based care, bevacizumab was the least used anti-VEGF treatment. COVID-19 correlated with a larger decrease in the utilization of all three anti-VEGF drugs.

Cost-effectiveness of Aflibercept Monotherapy vs Bevacizumab First Followed by Aflibercept If Needed for Diabetic Macular Edema.

Importance: The DRCR Retina Network Protocol AC showed no significant difference in visual acuity outcomes over 2 years between treatment with aflibercept monotherapy and bevacizumab first with switching to aflibercept for suboptimal response in treating diabetic macular edema (DME). Understanding the estimated cost and cost-effectiveness of these approaches is important. Objective: To evaluate the cost and cost-effectiveness of aflibercept monotherapy vs bevacizumab-first strategies for DME treatment. Design, Setting, and Participants: This economic evaluation was a preplanned secondary analysis of a US randomized clinical trial of participants aged 18 years or older with center-involved DME and best-corrected visual acuity of 20/50 to 20/320 enrolled from December 15, 2017, through November 25, 2019. Interventions: Aflibercept monotherapy or bevacizumab first, switching to aflibercept in eyes with protocol-defined suboptimal response. Main Outcomes and Measures: Between February and July 2022, the incremental cost-effectiveness ratio (ICER) in cost per quality-adjusted life-year (QALY) over 2 years was assessed. Efficacy and resource utilization data from the randomized clinical trial were used with health utility mapping from the literature and Medicare unit costs. Results: This study included 228 participants (median age, 62 [range, 34-91 years; 116 [51%] female and 112 [49%] male; 44 [19%] Black or African American, 60 [26%] Hispanic or Latino, and 117 [51%] White) with 1 study eye. The aflibercept monotherapy group included 116 participants, and the bevacizumab-first group included 112, of whom 62.5% were eventually switched to aflibercept. Over 2 years, the cost of aflibercept monotherapy was $26 504 (95% CI, $24 796-$28 212) vs $13 929 (95% CI, $11 984-$15 874) for the bevacizumab-first group, a difference of $12 575 (95% CI, $9987-$15 163). The aflibercept monotherapy group gained 0.015 (95% CI, -0.011 to 0.041) QALYs using the better-seeing eye and had an ICER of $837 077 per QALY gained compared with the bevacizumab-first group. Aflibercept could be cost-effective with an ICER of $100 000 per QALY if the price per dose were $305 or less or the price of bevacizumab was $1307 per dose or more. Conclusions and Relevance: Variability in individual needs will influence clinician and patient decisions about how to treat specific eyes with DME. While the bevacizumab-first group costs still averaged approximately $14 000 over 2 years, this approach, as used in this study, may confer substantial cost savings on a societal level without sacrificing visual acuity gains over 2 years compared with aflibercept monotherapy.

Assessment of Retinal Changes Following Intravitreal Aflibercept in 2 Patients With Von Hippel-Lindau Disease-Related Retinal Capillary Hemangioblastoma.

This case report of 2 patients describes peripheral Von Hippel-Lindau disease associated with a series of aflibercept injections.

Diabetic macular edema and proliferative diabetic retinopathy treated with anti-vascular endothelial growth factor under the reimbursement policy in Taiwan.

The purpose of this retrospective interventional case series is to compare the functional and anatomical outcomes in eyes with diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) treated intravitreally with aflibercept or ranibizumab under the Taiwan National Insurance Bureau reimbursement policy. 84 eyes were collected and all eyes were imaged with spectral-domain optical coherence tomography (SD-OCT), color fundus photographs (CFPs), and fluorescein angiography (FA). At 24 months after therapy initiation, the logMAR BCVA improved from 0.58 ± 0.33 to 0.47 ± 0.38 (p < 0.01), the CRT decreased from 423.92 ± 135.84 to 316.36 ± 90.02 (p < 0.01), and the number of microaneurysms decreased from 142.14 ± 57.23 to 75.32 ± 43.86 (p < 0.01). The mean injection count was 11.74 ± 5.44. There was no intergroup difference in logMAR BCVA (p = 0.96), CRT (p = 0.69), or injection count (p = 0.81). However, the mean number of microaneurysms was marginally reduced (p = 0.06) in eyes treated with aflibercept at the end of the follow-up, and the incidence rates of supplementary panretinal photocoagulation (PRP) (p = 0.04) and subthreshold micropulse laser (SMPL) therapy sessions (p = 0.01) were also reduced. Multivariate analysis revealed that only initial logMAR BCVA influenced the final VA improvements (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.21 ~ 0.93, p < 0.01); in contrast, age (OR - 0.38, 95% CI - 6.97 ~ - 1.85, p < 0.01) and initial CRT (OR 0.56, 95% CI 0.34 ~ 0.84, p < 0.01) both influenced the final CRT reduction at 24 months. To sum up, both aflibercept and ranibizumab are effective in managing DME with PDR in terms of VA, CRT and MA count. Eyes receiving aflibercept required less supplementary PRP and SMPL treatment than those receiving ranibizumab. The initial VA influenced the final VA improvements at 24 months, while age and initial CRT were prognostic predictors of 24-month CRT reduction.

Intravitreal Pharmacotherapies for Diabetic Macular Edema: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the evidence on the safety and efficacy of current anti-vascular endothelial growth factor (VEGF) and intravitreal corticosteroid pharmacotherapies for the treatment of diabetic macular edema (DME). METHODS: Literature searches were last conducted on May 13, 2020, in the PubMed database with no date restrictions and limited to articles published in English. The combined searches yielded 230 citations, of which 108 were reviewed in full text. Of these, 31 were deemed appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. RESULTS: Only the 21 articles with level I evidence were included in this assessment. Seventeen articles provided level I evidence for 1 or more anti-VEGF pharmacotherapies, including ranibizumab (14), aflibercept (5), and bevacizumab (2) alone or in combination with other treatments for DME. Level I evidence was identified in 7 articles on intravitreal corticosteroid therapy for treatment of DME: triamcinolone (1), dexamethasone (4), and fluocinolone acetonide (2). CONCLUSIONS: Review of the available literature indicates that intravitreal injections of anti-VEGF agents and corticosteroids are efficacious treatments for DME. Elevated intraocular pressure and cataract progression are important potential complications of corticosteroid therapy. Further evidence is required to assess the comparative efficacy of these therapies. Given the limited high-quality comparative efficacy data, choice of therapy must be individualized for each patient and broad therapeutic access for patients is critical to maximize outcomes.

Costs comparison of treating diabetic macular edema with aflibercept, ranibizumab or dexamethasone at 1 year in France (INVICOST study).

PURPOSE: INVICOST, a medico-economic analysis, compared costs of managing treatment-naive patients with diabetic macular edema (DME) receiving intravitreal injections (IVIs) of aflibercept (AFL), dexamethasone implant (DXI) or ranibizumab (RAN) over 1 year. METHODS: Healthcare resource use and associated costs were estimated using individual patient data from INVICTUS, a prospective, open-label, monocentric study. Healthcare costs comprised direct medical costs such as drug acquisition and administration, consultations and ophthalmological procedures. Costs were assessed from the French National Health Insurance perspective using published national tariffs expressed in 2019 euros. RESULTS: Of the 60 treated eyes, 48 had no treatment switch; 14 received AFL, 19 received DXI and 15 received RAN. AFL-treated eyes received an average of 6.5 IVIs, DXI-treated patients received 2 IVIs and RAN-treated received 6.8 IVIs. All treated eyes received an initial prescription for adjunctive ocular medications and 349 follow-up procedures were performed including an average of 3.9 optical coherence tomography and 3.2 retinography procedures per eye. Average total direct cost of per-eye treatment was €4516 (€1128-€8257). Average cost was €5782 for eyes treated with AFL, €2779 with DXI and €5536 with RAN. Drug therapy was the cost driver: €4394 (76%) for AFL, €1915 for DXI (69%) and €4268 (77%) for RAN. CONCLUSION: The difference in total treatment cost is largely explained by the significantly lower frequency of IVI and annual cost of therapy with DXI, compared with AFL and RAN. INVICOST is the first study comparing treatment costs with AFL, DXI and RAN in France in current clinical practice.

Burden of disease assessment in patients with neovascular age-related macular degeneration in Spain: Results of the AMD-MANAGE study.

BACKGROUND/AIMS: The present study evaluates the burden of neovascular age-related macular degeneration (nAMD) to Healthcare System and patients, describing the management and treatment effectiveness in routine clinical practice in Spain. METHODS: Observational, non-interventional, cross-sectional, retrospective (24 months), multicentre study including patients who started treatment with licensed vascular endothelial growth factor inhibitors (anti-VEGF) for nAMD with a minimum follow up of 24 months. RESULTS: 126 evaluable patients were included with mean (SD) age of 79.1 (7.5) years. From diagnosis, it took a mean (SD) of 0.5 (0.5) months for the first treatment. Throughout 24 months, mean (SD) number of visits per patient was 16.0 (5.0), 9.4 (4.3) associated intravitreal injection. There were 1186 injection visits, 53.6% of them only with injection and 46.3% with injection and tests. After loading phase, preferred treatment regimens were T&E (46.0%), PRN (44.4%), fixed regimen (4.0%), and others (5.6%). Total number of visits in patients with T&E and PRN were 16.5 (5.7) and 15.5 (4.7), respectively. After complete loading phase, mean (SD) time between two consecutive treatment injections was 2.2 (1.6) months. 27.8% patients underwent a treatment change, being lack of response the most frequent reason to change (43.2%). Mean (SD) best-corrected visual acuity change was 2.1 (15.9) letters at 24 months. CONCLUSION: This study showed an important burden to Healthcare System and patients related to monitoring visits. More efficacious and longer lasting treatments could be useful to increase treatment intervals, thus reducing the burden of patients and caregivers and the use of healthcare resources.

Economic burden of age-related macular degeneration in routine clinical practice: the RAMDEBURS study.

PURPOSE: To describe and evaluate the main direct health costs, in routine clinical practice, of age-related macular degeneration (AMD) patients, from hospital perspective, in Spain. METHODS: Retrospective, multicenter, and observational study conducted on five third-level Spanish hospitals, between December 2018 and December 2019. The study included patients who were diagnosed of AMD before December 2018. Direct healthcare costs were obtained from a Spanish database. Study variables included demographic and clinical variables, and resources, such as treatment, diagnostic tests, medical examination, and surgery. Among the 1414 screened AMD patients, 1164 patients were included. In the overall study patients, the total cost was €5,386,511.0, with a mean cost per patient of €4627.6 ± 2383.9. The largest cost items were diagnostic examinations (€2.832.902,0) and vascular endothelial growth factor inhibitors (anti-VEGF) treatment (€2.038.257,2). Bevacizumab was administered to 325 (27.9%) patients, ranibizumab to 328 (28.2%), and aflibercept to 626 (53.8%); 115 (10.7%) patients received two anti-VEGF treatments, while 90 (7.7%) did not receive any. Over the course of the study, a total of 6,057 anti-VEGF injections were administered, with a mean (95% confidence interval) of 4.8 (4.4-5.2) injections per patient. Regarding safety, 29 patients experience injection-related adverse events, among them 12 patients had cataract and 11 ones elevated intraocular pressure (IOP). The incidence of endophthalmitis was 0.5% (6/1164). CONCLUSIONS: AMD was associated with considerable healthcare costs for regional healthcare systems. Diagnostic examinations, particularly OCT examinations, and anti-VEGF treatment represented the largest cost items.

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.

Opportunities and Challenges in Translational Research: The Development of Photodynamic Therapy and Anti-Vascular Endothelial Growth Factor Drugs.

The development of photodynamic therapy and anti-vascular endothelial growth factor agents have revolutionized the treatment of retinal diseases, transforming the retina subspecialty by ushering in an age of pharmacological treatments for a wide range of diseases, including age-related macular degeneration (AMD).

Cost Effectiveness of Ranibizumab vs Aflibercept vs Bevacizumab for the Treatment of Macular Oedema Due to Central Retinal Vein Occlusion: The LEAVO Study.

BACKGROUND: We aimed to assess the cost effectiveness of intravitreal ranibizumab (Lucentis), aflibercept (Eylea) and bevacizumab (Avastin) for the treatment of macular oedema due to central retinal vein occlusion. METHODS: We calculated costs and quality-adjusted life-years from the UK National Health Service and Personal Social Services perspective. We performed a within-trial analysis using the efficacy, safety, resource use and health utility data from a randomised controlled trial (LEAVO) over 100 weeks. We built a discrete event simulation to model long-term outcomes. We estimated utilities using the Visual-Functioning Questionnaire-Utility Index, EQ-5D and EQ-5D with an additional vision question. We used standard UK costs sources for 2018/19 and a cost of £28 per bevacizumab injection. We discounted costs and quality-adjusted life-years at 3.5% annually. RESULTS: Bevacizumab was the least costly intervention followed by ranibizumab and aflibercept in both the within-trial analysis (bevacizumab: £6292, ranibizumab: £13,014, aflibercept: £14,328) and long-term model (bevacizumab: £18,353, ranibizumab: £30,226, aflibercept: £35,026). Although LEAVO did not demonstrate bevacizumab to be non-inferior for the visual acuity primary outcome, the three interventions generated similar quality-adjusted life-years in both analyses. Bevacizumab was always the most cost-effective intervention at a threshold of £30,000 per quality-adjusted life-year, even using the list price of £243 per injection. CONCLUSIONS: Wider adoption of bevacizumab for the treatment of macular oedema due to central retinal vein occlusion could result in substantial savings to healthcare systems and deliver similar health-related quality of life. However, patients, funders and ophthalmologists should be fully aware that LEAVO could not demonstrate that bevacizumab is non-inferior to the licensed agents.

Factors Associated With a Patient's Decision to Select a Cost-effective vs the Most Effective Therapy for Their Own Eye Disease.

Importance: Ten percent of the Medicare Part B budget is spent on aflibercept, used to treat a myriad of ocular neovascular diseases. A substantial portion of these costs can be attributed to a few hundred ophthalmologists, raising concerns regarding the influence of pharmaceutical companies on the choice of medication by a relatively small group of clinicians. One approach to protect patients' health care interests is to include them in deliberations on the choice of therapy for their eye disease. Objective: To examine factors associated with patients' choice between an effective and less expensive off-label drug or a more effective, but also more expensive, US Food and Drug Administration (FDA)-approved drug. Design, Setting, and Participants: This retrospective cohort analysis used data from the satellite office of a tertiary referral center from August 2, 2013, to April 9, 2018. Insured patients initiating treatment with anti-vascular endothelial growth factor were included in the analysis. Data were analyzed from March 26, 2018, to June 10, 2020. Interventions: Patients were asked to choose between bevacizumab (approximately $100 per dose), a chemotherapy that is effective, but not FDA approved, for the treatment of ocular vascular disease, or aflibercept (approximately $2000 per dose), an FDA-approved drug for ocular vascular disease that may be more effective than bevacizumab in some patients. Independent of this choice, patients were separately asked by a study coordinator to participate in an invasive clinical study for which they would not be compensated, there was a small risk for an adverse event, and they would not personally benefit from participating (a surrogate marker for altruism). Main Outcomes and Measures: Factors associated with patients' choice of medication, including age, sex, ocular disease, race, and participation in an invasive clinical study. Results: A total of 189 patients were included in the analysis (106 women [56%]; mean [SEM] age, 74.6 [0.8] years). Despite being told that it may not be as effective as aflibercept, 100 patients (53%) selected bevacizumab for their own eye care. An act of altruism (ie, participation in an invasive clinical study) when the patient was making a choice between the 2 drugs was associated with a patient's choice of bevacizumab (odds ratio [OR], 7.03; 95% CI, 2.27-21.80; P < .001); the OR for selecting bevacizumab for patients who never agreed to participate in the clinical study was 0.45 (95% CI, 0.25-0.83; P = .001). Age (OR, 1.00; 95% CI, 0.97-1.03; P = .86), race (OR, 0.70; 95% CI, 0.41-1.22; P = .21), sex (OR, 0.72; 95% CI, 0.39-1.35; P = .31), presence of diabetes (OR, 1.52; 95% CI, 0.59-3.93; P = .39), and type of eye disease (OR, 0.56; 95% CI, 0.30-1.04; P = .07) were not associated with choice of therapy. Conclusions and Relevance: These findings suggest that clinicians must consider the ethical implications of the influence of altruism when patients participate in the decision between cost-effective vs the most effective medicines for their own health care.

Using optical coherence tomography angiography in assessment of the anti-vascular endothelial growth factor effect for pathological vascular tissue in age-related macular degeneration and polypoidal choroidal vasculopathy.

PURPOSE: Using optical coherence tomography angiography to assess and compare changes in pathological vascular tissue, including choroidal neovascularization in neovascular age-related macular degeneration and polypoidal complex in polypoidal choroidal vasculopathy, after treatment with anti-vascular endothelial growth factor. METHODS: This is a retrospective observational case series study. Clinical data were collected, including that on the best-corrected visual acuity and images of spectrum domain optical coherence tomography and optical coherence tomography angiography of consecutive patients with macula-involved lesions, active pathological vascular tissue in neovascular age-related macular degeneration, and polypoidal complex in polypoidal choroidal vasculopathy who were treated with anti-vascular endothelial growth factor injection. The primary outcome measures were the lesion area, flow density, and flow area of the pathological vascular tissue obtained in optical coherence tomography angiography before treatment, as well as week-1 (W1) and week-5 (W5) after treatment. The secondary outcome measures were the best-corrected visual acuity and the anatomic changes in spectrum domain optical coherence tomography at the same periods. RESULTS: A total of 86 eyes in 79 patients (mean age: 73.10 ± 10.10 (range = 50-91) years, 45 males (57%), of which two eyes were treatment-naïve) underwent one section of intravitreal treatment. Of which 44 eyes (40 patients) were diagnosed as typical neovascular age-related macular degeneration and 42 eyes (39 patients) as polypoidal choroidal vasculopathy. The sensitivity for detecting choroidal neovascularization in neovascular age-related macular degeneration and polypoidal complex in polypoidal choroidal vasculopathy was 75.00% (33/44) and 69.05% (29/42), respectively. There was no significant difference in the detection rate between neovascular age-related macular degeneration and polypoidal choroidal vasculopathy (p = 0.54). In the detectable group, there were significant decrease in lesion area and flow area in the optical coherence tomography angiography images after anti-vascular endothelial growth factor treatment in both the neovascular age-related macular degeneration group (lesion area: W1 = -26.94 ± 19.50%, W5 = -35.52 ± 30.85%, all ps < 0.001; flow area: W1 = -26.22 ± 25.23%, W5 = -32.24 ± 32.07%, all ps < 0.001) and the polypoidal choroidal vasculopathy group (lesion area: W1 = -25.19 ± 20.27%, W5 = -31.55 ± 27.04%, all ps < 0.001; flow area: W1 = -21.83 ± 26.29%, W5 = -28.31 ± 30.72%, all ps < 0.001). The central subfield retinal thickness in spectrum domain optical coherence tomography also showed similar amelioration in both groups. However, the flow density in optical coherence tomography angiography image and the visual outcome did not reveal any significant difference before or after intravitreal injections, and neither were there significant differences between the neovascular age-related macular degeneration and polypoidal choroidal vasculopathy groups. Concerning the effect on the optical coherence tomography angiography images of pathological vascular tissue, there were no statistical differences among different anti-vascular endothelial growth factor agents (i.e. aflibercept, ranibizumab, and bevacizumab). CONCLUSION: Our study revealed that optical coherence tomography angiography can be used noninvasively and quantitatively to assess the detailed pathologic vascular structures in both neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Our study also demonstrated that anti-vascular endothelial growth factor could effectively decrease the lesion size and flow area of both the choroidal neovascularization in neovascular age-related macular degeneration cases and the polypoidal complex in polypoidal choroidal vasculopathy cases; the effects were similar in both diseases.

Radiomics-based assessment of ultra-widefield leakage patterns and vessel network architecture in the PERMEATE study: insights into treatment durability.

AIM: To evaluate the potential of radiomics-based ultra-widefield fluorescein angiography (UWFA)-derived imaging biomarkers in retinal vascular disease for predicting therapeutic durability of intravitreal aflibercept injection (IAI). METHODS: The Peripheral and Macular Retinal Vascular Perfusion and Leakage Dynamics in Diabetic Macular Edema and Retinal Venous Occlusions During Intravitreal Aflibercept Injection (IAI) Treatment for Retinal Edema (PERMEATE) study prospectively evaluated quantitative UWFA dynamics in diabetic macular oedema or macular oedema secondary to retinal vascular occlusion. 27 treatment-naïve eyes were treated with 2 mg IAI q4 weeks for the first 6 months, and then administered q8 weeks. Morphological and graph-based attributes were used to model the spatial distribution of leakage areas, while tortuosity measures were used to model the vessel network disorder. Eyes were grouped based on functional tolerance of the first 8-week treatment interval challenge. 'Non-rebounders' (N=15) maintained/improved best-corrected visual acuity (BCVA) following the 8-week challenge. 'Rebounders' (N=12) exhibited worsened BVCA. The image biomarkers were used with a machine learning classifier to preliminarily evaluate their ability to predict BCVA stability. RESULTS: Two new UWFA image-derived biomarkers were identified and extracted. The cross-validated area under the receiver operating characteristic curve (AUC) was 0.77±0.14 using baseline leakage distribution features and 0.73±0.10 for the UWFA baseline tortuosity measures. Additionally, the change in vascular tortuosity between month 4 and baseline yielded an AUC of 0.73±0.08. Three baseline clinical features of letter score, macular volume and central subfield thickness yielded a corresponding AUC of 0.42±0.09. CONCLUSIONS: Two computer-extracted UWFA radiomics-based descriptors were identified as potential biomarkers for predicting treatment durability and tolerance of longer treatment intervals. Conventional treatment parameters were not significantly different between these same groups.

Cost-consequence analysis of extended loading dose of anti-VEGF treatment in diabetic macular edema patients.

BACKGROUND: The DRCR.net Protocol T clinical trial assessed the comparative efficacy and safety of anti-VEGF treatments including aflibercept, ranibizumab and bevacizumab in diabetic macular edema (DME). Post -hoc analyses showed that after a 12-week induction period, there was still DME resolution in an increasing number of patients through week 24. PURPOSE: To assess clinical and cost consequences of extending the anti-VEGF loading dose from 3 to 6 monthly injections in patients with persistent DME in Spain. METHODS: From a hospital pharmacy perspective, a cost-consequence analysis model was developed to estimate the incremental cost needed to obtain an additional response at month 6. To estimate drug treatment costs, ex-factory prices (€, 2019) were considered for aflibercept, ranibizumab and bevacizumab. Response/nonresponse rates at 3/6 months were obtained from the Protocol T 24-week post hoc analysis (n = 546). Persistent DME was present in 50.8 and 31.6% of the 190 aflibercept-treated patients at month 3 and month 6, respectively. Of the 176 ranibizumab- and 180 bevacizumab-treated patients, 53.2 and 72.9%, respectively, had persistent DME at month 3, and 41.5 and 65.6%, respectively, had persistent DME at month 6. Sensitivity analysis considered the split of bevacizumab vials. RESULTS: Extending the loading dose in nonresponder patients would cost €214,862.57, €208,488.98 and €134,483.16 to obtain 37, 21 and 13 additional aflibercept, ranibizumab and bevacizumab responder patients, respectively. The total number of extended injections (months 3-6) used in patients with persistent DME at month 6 was 180, 219 and 354 for aflibercept, ranibizumab and bevacizumab, respectively. CONCLUSIONS: To extend the anti-VEGF loading dose from 3 to 6 injections necessitates investing €5882.77 (8 injections), €10,091.03 (14 injections) and €10,198.59 (30 injections) per additional responder patient (3-month nonresponders and 6-month responders) to aflibercept, ranibizumab and bevacizumab, respectively. For the total of patients treated, on average €7927.02 (14 injections) per additional responder patient would be needed.

Cost-minimization Analysis of Ranibizumab versus Aflibercept in the Treatment of Neovascular Age-related Macular Degeneration in Colombia.

BACKGROUND: In 2020 Colombia may expect to have close to 231,700 patients with neovascular age-related macular degeneration (ARMD). Treatment of neovascular ARMD involves the sequential Intra-vitreal injections of anti-vascular endothelial growth factor (anti-VEGF therapy) medications. The efficacy and safety of anti-VEGF therapy on a treat-and-extend (T&E) dosing scheme are similar when ranibizumab or aflibercept are administered. Objective : A cost-minimization analysis from the payer`s perspective in Colombia projects treatment expenses of anti-VEGF therapy using aflibercept or ranibizumab on T&E regimens for the treatment of neovascular ARMD. Methods : A model projects the expenses of the compared treatment regimens for two and five-year periods beginning on February 2020. The model used information from clinical trials, case series and meta-analyses on the compared treatment regimens, demographic, epidemiologic and economic data originated from the Colombian government sources. A 3% discount rate was applied. Results : Projected cost differences in favor of ranibizumab after two and five-year treatment periods beginning February 2020 could be close to U.S. $ 4,861 and U.S $ 7,241 per treated eye, respectively. If all patients with unilateral and bilateral neovascular ARMD in Colombia were to receive appropriate anti-VEGF therapy for two years, the projected expected cost difference in favor of ranibizumab could be close to U.S. $ 462,717,092 dollars. Conclusion : Within the Colombian healthcare setting anti-VEGF therapy on a T&E regimen utilizing ranibizumab for neovascular ARMD may be cost-saving compared with employing aflibercept. Despite cost favorability, ranibizumab should not be the only therapeutic option since in clinical practice alternatives are required.

Comparative Cost-effectiveness of Aflibercept and Ramucirumab in Combination with Irinotecan and Fluorouracil-based Therapy for the Second-line Treatment of Metastatic Colorectal Cancer in Japan.

PURPOSE: The addition of aflibercept (AFL) or ramucirumab (RAM) to folinic acid, fluorouracil, and irinotecan (FOLFIRI) prolongs overall survival and progression-free survival compared with FOLFIRI alone in patients with metastatic colorectal cancer (mCRC) as second-line therapy. Although these combination regimens are recommended among the standard therapies, significant additional cost is a concern. The comparative cost-effectiveness of AFL and RAM was examined from the perspective of the Japanese health care payer. METHODS: A partitioned survival analysis was constructed. The data sources were the VELOUR (Aflibercept Versus Placebo in Combination With Irinotecan and 5-FU in the Treatment of Patients With Metastatic Colorectal Cancer After Failure of an Oxaliplatin Based Regimen) and RAISE (Ramucirumab Versus Placebo in Combination With Second-Line FOLFIRI in Patients With Metastatic Colorectal Carcinoma That Progressed During or After First-Line Therapy With Bevacizumab, Oxaliplatin, and a Fluoropyrimidine) trials, which compared FOLFIRI alone with AFL or RAM in second-line treatment for mCRC. The cost and effectiveness of the combination of AFL or RAM with FOLFIRI were compared with those of FOLFIRI alone and examined between both agents in a 10-year time horizon. The health outcomes were life-years (LYs) and quality-adjusted life-years (QALYs). The costs were 2019 revisions to the drug prices and medical fees. The robustness of the model was verified by 1-way sensitivity analyses and a probability sensitivity analysis. A 2% annual discount was applied to the expenses and QALYs. A willingness-to-pay threshold of ¥7.5 million was used. FINDINGS: Compared with FOLFIRI alone, combination AFL or RAM with FOLFIRI had incremental effects of 0.173 QALYs (0.253 LYs) and 0.137 QALYs (0.197 LYs), incremental costs of ¥3,423,481 (US $31,010) and ¥5,766,106 (US $52,229), and incremental cost-effectiveness ratios of ¥19, 836, 504 (US $179,678) and ¥41, 947, 989 (US $379,964) per QALY, respectively. Results of 1-way sensitivity analyses and probability sensitivity analysis all exceeded a willingness-to-pay threshold of ¥7.5 million. In the comparison of the 2 agents, AFL was a dominant over RAM. IMPLICATIONS: Adding AFL or RAM to FOLFIRI in the second line of mCRC treatment was not cost-effective in the Japanese health care system. On the basis of the results of this study, in the treatment of mCRC, it will be necessary to adjust the prices of AFL and RAM with the improvement of clinical parameters, such as survival time and adverse events. Of the 2 agents, AFL was more cost-effective than RAM.

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.