ABSTRACT
BACKGROUND: To evaluate the impact of reimbursement criteria change on the utilization pattern of anti-vascular endothelial growth factor (anti-VEGF) among patients with wet age-related macular degeneration (wAMD) and diabetic macular edema (DME) separately in Taiwan. METHODS: An interrupted time series analysis (ITSA) was performed using Taiwan's National Health Insurance (NHI) database, and patients with wAMD or DME diagnosis at the first injection of anti-VEGF agents was identified from 2011 to 2019. The outcome of interest was treatment gaps between injections of anti-VEGF. This outcome was retrieved quarterly, and the study period was divided into three phases in wAMD (two criteria changed in August 2014 [intervention] and December 2016 [intervention]) and two phases in DME (three consecutive criteria changed in 2016 [intervention]). Segmented regression models adjusted for autocorrelation were used to estimate the change in level and the change in slope of the treatment gaps between each anti-VEGF injection. RESULTS: The treatment gaps between each anti-VEGF injection decreased from 2011 to 2019. The cancellation of the annual three needles limitation was associated with significantly shortened treatment gaps between the third and fourth needles (wAMD change in level: -228 days [95% CI -282, -173], DME change in level: -110 days [95% CI -141, -79]). The treatment gap between the fifth and sixth needles revealed a similar pattern but without significant change in DME patients. Other treatment gaps revealed considerable change in slopes in accordance with criteria changes. CONCLUSION: This is the first nationwide study using ITSA to demonstrate the impact of reimbursement policy on treatment gaps between each anti-VEGF injection. After canceling the annual limitation, we found that the treatment gaps significantly decreased among wAMD and DME patients. The shortened treatment gaps might further link to better visual outcomes according to previous studies. The different impacts from criteria changes can assist future policy shaping. Future studies were warranted to explore whether such changes are associated with the benefits of visual effects.
Subject(s)
Angiogenesis Inhibitors , Diabetic Retinopathy , Interrupted Time Series Analysis , Macular Edema , Vascular Endothelial Growth Factor A , Humans , Macular Edema/drug therapy , Macular Edema/economics , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/economics , Male , Female , Angiogenesis Inhibitors/economics , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/administration & dosage , Taiwan , Aged , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Wet Macular Degeneration/drug therapy , Wet Macular Degeneration/economics , Intravitreal Injections , Reimbursement Mechanisms , Middle Aged , National Health Programs/economics , National Health Programs/statistics & numerical data , Ranibizumab/economics , Ranibizumab/therapeutic use , Ranibizumab/administration & dosage , Aged, 80 and overABSTRACT
BACKGROUND: Bevacizumab shows superior efficacy in cerebral radiation necrosis (CRN) therapy, but its economic burden remains heavy due to the high drug price. This study aims to evaluate the cost-effectiveness of bevacizumab for CRN treatment from the Chinese payers' perspective. METHODS: A decision tree model was developed to compare the costs and health outcomes of bevacizumab and corticosteroids for CRN therapy. Efficacy and safety data were derived from the NCT01621880 trial, which compared the effectiveness and safety of bevacizumab monotherapy with corticosteroids for CRN in nasopharyngeal cancer patients, and demonstrated that bevacizumab invoked a significantly higher response than corticosteroids (65.5% vs. 31.5%, Pâ¯< 0.001) with no significant differences in adverse events between two groups. The utility value of the "non-recurrence" status was derived from real-world data. Costs and other utility values were collected from an authoritative Chinese network database and published literature. The primary outcomes were total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). The uncertainty of the model was evaluated via one-way and probabilistic sensitivity analyses. RESULTS: Bevacizumab treatment added 0.12 (0.48 vs. 0.36) QALYs compared to corticosteroid therapy, along with incremental costs of $ 2010 ($ 4260 vs. $ 2160). The resultant ICER was $ 16,866/QALY, which was lower than the willingness-to-pay threshold of $ 38,223/QALY in China. The price of bevacizumab, body weight, and the utility value of recurrence status were the key influential parameters for ICER. Probabilistic sensitivity analysis revealed that the probability of bevacizumab being cost-effectiveness was 84.9%. CONCLUSION: Compared with corticosteroids, bevacizumab is an economical option for CRN treatment in China.
Subject(s)
Bevacizumab , Cost-Benefit Analysis , Quality-Adjusted Life Years , Radiation Injuries , Bevacizumab/therapeutic use , Bevacizumab/economics , Humans , China , Radiation Injuries/economics , Radiation Injuries/etiology , Decision Trees , Nasopharyngeal Neoplasms/radiotherapy , Nasopharyngeal Neoplasms/economics , Nasopharyngeal Neoplasms/drug therapy , Necrosis , Adrenal Cortex Hormones/therapeutic use , Adrenal Cortex Hormones/economics , Angiogenesis Inhibitors/economics , Angiogenesis Inhibitors/therapeutic use , Antineoplastic Agents, Immunological/economics , Antineoplastic Agents, Immunological/therapeutic use , Male , Drug Costs , Middle Aged , Cost-Effectiveness AnalysisABSTRACT
OBJECTIVE: Current cost-effectiveness analyses (CEA) emphasize drug costs as the differentiator between NICE recommended anti-VEGF treatments but may neglect real-world non-drug costs of running nAMD services in the UK. To address this, this study identified real-world non-drug service cost items relevant to UK NHS nAMD clinics, including costs arising from operational strain (demand exceeding capacity). METHODS: Cost items were identified by a structured literature review of peer-reviewed and grey literature, and an expert panel of 10 UK-based ophthalmologists with relevance to real-world practice. These items underwent meta-synthesis and were then determined in a consensus exercise. RESULTS: Of 237 cost items identified, 217 (91.6%) met the consensus threshold of >0.51 and were included in the nAMD Service Non-Drug Cost Instrument (nAS). Sensitivity of cost items taken from UK Health Technology Assessment (HTA) using the nAS as the reference standard was low (HTAmin: 1.84%, 95% CI 0.50-4.65%; HTAmax: 70.51%, 95% CI 63.96-76.49%). False negative rates showed variable likelihood of misclassifying a service by cost burden depending on prevalence. Scenario analysis using cost magnitudes estimated annual per-patient clinic cost at £845 (within capacity) to £13,960 (under strain) compared to an HTAmin estimate of £210. Accounting for cost of strain under an assumed 50% increase in health resource utilization influenced cost-effectiveness in a hypothetical genericisation scenario. CONCLUSION: Findings suggested that HTA underestimates UK NHS nAMD clinic cost burden with cost of strain contributing substantial additional unmeasured expense with impact on CEA. Given potential undertreatment due to strain, durability is suggested as one of the relevant factors in CEA of nAMD anti-VEGF treatments due to robustness under limited capacity conditions affecting UK ophthalmology services.
When considering how well treatments work versus how much they cost, the focus is usually only on the price of the medicine itself. However, other real-world costs exist. In the UK, when treating certain eye problems such as neovascular age-related macular degeneration (nAMD), there are additional expenses related to running clinics and managing treatments that often go unnoticed. To get a better understanding of these hidden costs, the study examined factors like clinic workload and the extra expenses that come with it. Ten eye doctors in the UK were consulted for their expert opinions and numerous research papers were reviewed to identify these additional costs. The study grouped different costs in a tool called the nAMD Service Non-Drug Cost Instrument (nAS). When the findings of the nAS tool were compared to the usual methods of calculating costs, it was found that the conventional approach overlooked many of the actual expenses. Busy clinics face unique challenges, such as higher operational costs associated with staffing for extended hours, emergency appointments, extended waiting times and the potential to miss optimal treatment windows. This can lead to disease progression and the onset of comorbidities, which require more complex and costly treatments. Recognizing these real costs is crucial when making decisions about treatments, especially when treatments require more frequent visits to eye clinics. This study emphasizes the importance of considering all expenses, not just the obvious ones like medication and doctor visits when determining the most effective way to manage eye conditions like nAMD in the UK.
Subject(s)
Cost-Benefit Analysis , Humans , United Kingdom , Health Care Costs/statistics & numerical data , Angiogenesis Inhibitors/economics , Angiogenesis Inhibitors/therapeutic useABSTRACT
Diabetic macular edema (DME) is a degenerative disease of the macular area in diabetes mellitus and can lead to vision loss, disability, and significantly reduced quality of life. Faricimab is the only bispecific antibody for DME therapy that targets two pathogenic pathways (Ang-2 and VEGF-A). PURPOSE: This study comparatively evaluates the clinical and economic feasibility of faricimab and other angiogenesis inhibitors in patients with DME. MATERIAL AND METHODS: This article analyzed literature on the efficacy and safety of intravitreal injections (IVI) of ranibizumab 0.5 mg, aflibercept 2 mg, and faricimab 6 mg. A model of medical care was developed for patients with DME receiving anti-angiogenic therapy. Pharmacoeconomic analysis was performed using cost minimization and budget impact analysis (BIA) methods. Modeling time horizon was 2 years. The research was performed from the perspective of the healthcare system of the Russian Federation. RESULTS: The efficacy and safety of faricimab in a personalized regimen (up to one IVI in 16 weeks) are comparable to those of aflibercept and ranibizumab, administered in various regimens. The use of faricimab is associated with the lowest number of IVIs. Over 2 years, the maximum costs of drug therapy were associated with the use of ranibizumab (about 914 thousand rubles), while the minimum costs were associated with the use of faricimab (614 thousand rubles). The reduction in inpatient care costs with faricimab therapy was 36% compared to aflibercept (216 and 201 thousand rubles in inpatient and day hospitals, respectively) and 82% compared to ranibizumab (486 and 451 thousand rubles in inpatient and day hospitals, respectively). BIA demonstrated that the use of faricimab will reduce the economic burden on the healthcare system by 11.3 billion rubles (9.8%) over 2 years. CONCLUSION: The use of faricimab is a cost-effective approach to treatment of adult patients with DME in Russia.
Subject(s)
Angiogenesis Inhibitors , Diabetic Retinopathy , Economics, Pharmaceutical , Macular Edema , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins , Humans , Macular Edema/drug therapy , Macular Edema/etiology , Macular Edema/economics , Angiogenesis Inhibitors/economics , Angiogenesis Inhibitors/administration & dosage , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/economics , Russia , Recombinant Fusion Proteins/economics , Recombinant Fusion Proteins/administration & dosage , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Intravitreal Injections , Ranibizumab/administration & dosage , Ranibizumab/economics , Cost-Benefit Analysis , Antibodies, Bispecific/economics , Antibodies, Bispecific/administration & dosage , Treatment OutcomeABSTRACT
OBJECTIVES: This study aimed to evaluate the cost-effectiveness of anti-vascular endothelial growth factor drugs (anti-VEGFs) compared with panretinal photocoagulation (PRP) for treating proliferative diabetic retinopathy (PDR) in the United Kingdom. METHODS: A discrete event simulation model was developed, informed by individual participant data meta-analysis. The model captures treatment effects on best corrected visual acuity in both eyes, and the occurrence of diabetic macular edema and vitreous hemorrhage. The model also estimates the value of undertaking further research to resolve decision uncertainty. RESULTS: Anti-VEGFs are unlikely to generate clinically meaningful benefits over PRP. The model predicted anti-VEGFs be more costly and similarly effective as PRP, generating 0.029 fewer quality-adjusted life-years at an additional cost of £3688, with a net health benefit of -0.214 at a £20 000 willingness-to-pay threshold. Scenario analysis results suggest that only under very select conditions may anti-VEGFs offer potential for cost-effective treatment of PDR. The consequences of loss to follow-up were an important driver of model outcomes. CONCLUSIONS: Anti-VEGFs are unlikely to be a cost-effective treatment for early PDR compared with PRP. Anti-VEGFs are generally associated with higher costs and similar health outcomes across various scenarios. Although anti-VEGFs were associated with lower diabetic macular edema rates, the number of cases avoided is insufficient to offset the additional treatment costs. Key uncertainties relate to the long-term comparative effectiveness of anti-VEGFs, particularly considering the real-world rates and consequences of treatment nonadherence. Further research on long-term visual acuity and rates of vision-threatening complications may be beneficial in resolving uncertainties.
Subject(s)
Angiogenesis Inhibitors , Diabetic Retinopathy , Quality-Adjusted Life Years , Vascular Endothelial Growth Factor A , Female , Humans , Male , Middle Aged , Angiogenesis Inhibitors/economics , Angiogenesis Inhibitors/therapeutic use , Cost-Effectiveness Analysis , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/economics , Diabetic Retinopathy/therapy , Diabetic Retinopathy/surgery , Laser Coagulation/economics , Laser Coagulation/methods , Light Coagulation/economics , Light Coagulation/methods , Macular Edema/drug therapy , Macular Edema/economics , Macular Edema/therapy , Models, Economic , Treatment Outcome , United Kingdom , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visual AcuityABSTRACT
BACKGROUND/OBJECTIVES: Diabetic macular oedema (DMO) is a leading cause of blindness in developed countries, with significant disease burden associated with socio-economic deprivation. Distributional cost-effectiveness analysis (DCEA) allows evaluation of health equity impacts of interventions, estimation of how health outcomes and costs are distributed in the population, and assessments of potential trade-offs between health maximisation and equity. We conducted an aggregate DCEA to determine the equity impact of faricimab. METHODS: Data on health outcomes and costs were derived from a cost-effectiveness model of faricimab compared with ranibizumab, aflibercept and off-label bevacizumab using a societal perspective in the base case and a healthcare payer perspective in scenario analysis. Health gains and health opportunity costs were distributed across socio-economic subgroups. Health and equity impacts, measured using the Atkinson inequality index, were assessed visually on an equity-efficiency impact plane and combined into a measure of societal welfare. RESULTS: At an opportunity cost threshold of £20,000/quality-adjusted life year (QALY), faricimab displayed an increase in net health benefits against all comparators and was found to improve equity. The equity impact increased the greater the concerns for reducing health inequalities over maximising population health. Using a healthcare payer perspective, faricimab was equity improving in most scenarios. CONCLUSIONS: Long-acting therapies with fewer injections, such as faricimab, may reduce costs, improve health outcomes and increase health equity. Extended economic evaluation frameworks capturing additional value elements, such as DCEA, enable a more comprehensive valuation of interventions, which is of relevance to decision-makers, healthcare professionals and patients.
Subject(s)
Angiogenesis Inhibitors , Cost-Benefit Analysis , Diabetic Retinopathy , Health Equity , Macular Edema , Quality-Adjusted Life Years , Ranibizumab , Recombinant Fusion Proteins , Humans , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/economics , Macular Edema/drug therapy , Macular Edema/economics , Angiogenesis Inhibitors/economics , Angiogenesis Inhibitors/therapeutic use , United Kingdom , Health Equity/economics , Recombinant Fusion Proteins/economics , Recombinant Fusion Proteins/therapeutic use , Ranibizumab/economics , Ranibizumab/therapeutic use , Ranibizumab/administration & dosage , Male , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Intravitreal Injections , Female , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Bevacizumab/economics , Bevacizumab/therapeutic use , Drug Costs , Middle Aged , Cost-Effectiveness AnalysisABSTRACT
ABSTRACT: No US Food and Drug Administration- or European Medicines Agency-approved therapies exist for bleeding due to hereditary hemorrhagic telangiectasia (HHT), the second-most common inherited bleeding disorder worldwide. The current standard of care (SOC) includes iron and red cell supplementation, alongside the necessary hemostatic procedures, none of which target underlying disease pathogenesis. Recent evidence has demonstrated that bleeding pathophysiology is amenable to systemic antiangiogenic therapy with the anti-vascular endothelial growth factor bevacizumab. Despite its high cost, the addition of longitudinal bevacizumab to the current SOC may reduce overall health care resource use and improve patient quality of life. We conducted, to our knowledge, the first cost-effectiveness analysis of IV bevacizumab in patients with HHT with the moderate-to-severe phenotype, comparing bevacizumab added to SOC vs SOC alone. The primary outcome was the incremental net monetary benefit (iNMB) reported over a lifetime time horizon and across accepted willingness-to-pay thresholds, in US dollar per quality-adjusted life year (QALY). Bevacizumab therapy accrued 9.3 QALYs while generating $428 000 in costs, compared with 8.3 QALYs and $699 000 in costs accrued in the SOC strategy. The iNMB of bevacizumab therapy vs the SOC was $433 000. No parameter variation and no scenario analysis, including choice of iron supplementation product, changed the outcome of bevacizumab being a cost-saving strategy. Bevacizumab therapy also saved patients an average of 133 hours spent receiving HHT-specific care per year of life. In probabilistic sensitivity analysis, bevacizumab was favored in 100% of all 10 000 Monte Carlo iterations across base-case and all scenario analyses. Bevacizumab should be considered for more favorable formulary placement in the care of patients with moderate-to-severe HHT.
Subject(s)
Angiogenesis Inhibitors , Bevacizumab , Cost-Benefit Analysis , Telangiectasia, Hereditary Hemorrhagic , Bevacizumab/therapeutic use , Bevacizumab/economics , Humans , Telangiectasia, Hereditary Hemorrhagic/drug therapy , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/economics , Quality of Life , Male , Quality-Adjusted Life Years , FemaleABSTRACT
Introducción Brolucizumab es un nuevo fármaco antifactor de crecimiento endotelial vascular (anti-VEGF) administrado con una pauta fija de ocho o 12 semanas que en los estudios HAWK y HARRIER demostró ser no inferior a aflibercept con respecto a la mejor agudeza visual corregida, bajo una menor carga de administración. El objetivo del análisis fue comparar los costes directos sanitarios de ambos anti-VEGF como tratamiento en pacientes con degeneración macular asociada a la edad neovascular. Material y métodos Se realizó un análisis de minimización de costes bajo un horizonte temporal de 25 años y considerando el coste farmacológico, de administración, de pruebas de seguimiento y del manejo de eventos adversos. El uso de recursos fue obtenido de literatura relacionada y validada por expertos clínicos. Se llevaron a cabo diversos análisis de escenarios para comprobar la robustez de los resultados. Resultados Brolucizumab resultó con un menor coste por paciente en comparación con aflibercept, considerando el número de inyecciones derivadas de los estudios HAWK y HARRIER. Este resultado se mantuvo en los diferentes escenarios analizados, excepto frente al número de inyecciones de la pauta flexible de aflibercept del estudio ARIES, ya que la menor discontinuación de tratamiento con brolucizumab conlleva mantener el tratamiento de más pacientes. Al considerar la misma discontinuación, brolucizumab mantuvo los resultados observados en el caso base del análisis. Conclusiones El presente estudio muestra como la pauta de administración fija de brolucizumab puede ayudar a disminuir la carga asistencial para los centros sanitarios y los pacientes (AU)
Introduction Brolucizumab is a novel anti-vascular endothelial growth factor (anti-VEGF) drug administered in a fixed regimen of 8 or 12 weeks which, in the HAWK and HARRIER studies, was shown not to be inferior to aflibercept with respect to the best corrected visual acuity, with a less burdensome treatment regimen. The aim of the analysis was to compare the direct healthcare costs of both anti-VEGF as a treatment in patients with neovascular age-related macular degeneration.Material and methods A cost minimization analysis was performed under a 25-year time horizon and considering the drug costs, administration, follow-up tests, and management of adverse events. Resource use was obtained from the related literature and validated by clinical experts. Various scenario analysis were carried out to check the robustness of the results. Results Brolucizumab resulted in a lower cost per patient compared with aflibercept, considering the number of injections derived from the HAWK and HARRIER studies. This result was maintained in the different scenarios analysed, except for the number of injections of the flexible aflibercept regimen of the ARIES study, since the lower discontinuation of treatment with brolucizumab implies maintaining the treatment of more patients. Considering the same discontinuation, brolucizumab maintained the results observed in the base case of the analysis. Conclusions This study shows how the fixed administration regimen of brolucizumab can help reduce both healthcare and patients burden (AU)
Subject(s)
Costs and Cost Analysis , Angiogenesis Inhibitors/economics , Drug Costs , Intravitreal InjectionsABSTRACT
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.
Subject(s)
Drug Costs , Medicare Part B , Angiogenesis Inhibitors/economics , Bevacizumab/economics , Costs and Cost Analysis , Intravitreal Injections , Ranibizumab/economics , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins , United States , Vascular Endothelial Growth Factor A/antagonists & inhibitorsABSTRACT
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.
Subject(s)
Angiogenesis Inhibitors/economics , Antibodies, Monoclonal, Humanized/economics , Ranibizumab/economics , Recombinant Fusion Proteins/economics , Wet Macular Degeneration/drug therapy , Adolescent , Adult , Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Cost-Benefit Analysis , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Ranibizumab/therapeutic use , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Visual Acuity , Young AdultSubject(s)
Bevacizumab/therapeutic use , Drug Costs , Eye Diseases/drug therapy , Fee-for-Service Plans/economics , Medicare , Registries , Angiogenesis Inhibitors/economics , Angiogenesis Inhibitors/therapeutic use , Bevacizumab/economics , Eye Diseases/economics , Humans , Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors , United StatesABSTRACT
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.
Subject(s)
Altruism , Angiogenesis Inhibitors/economics , Bevacizumab/economics , Choice Behavior , Decision Making , Eye Diseases/drug therapy , Patient Participation , Recombinant Fusion Proteins/economics , Black or African American , Aged , Angiogenesis Inhibitors/therapeutic use , Asian , Bevacizumab/therapeutic use , Cohort Studies , Cost-Benefit Analysis , Diabetic Retinopathy/drug therapy , Drug Costs , Female , Humans , Macular Degeneration/drug therapy , Male , Middle Aged , Neovascularization, Pathologic/drug therapy , Odds Ratio , Off-Label Use , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Retinal Vein Occlusion/drug therapy , Retrospective Studies , Treatment Outcome , Visual Acuity , White PeopleABSTRACT
OBJECTIVES: Recent studies showed prolonged survival for advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients treated with both monotherapies and combined therapies. However, high costs limit clinical applications. Thus, we conducted this cost-effectiveness analysis to explore an optimal first-line treatment for advanced EGFR-mutant NSCLC patients. MATERIALS AND METHODS: Survival data were extracted from six clinical trials, including ARCHER1050 (dacomitinib vs. gefitinib); FLAURA (osimertinib vs. gefitinib/erlotinib); JO25567 and NEJ026 (bevacizumab +erlotinib vs. erlotinib); NEJ009 (gefitinib +chemotherapy vs. gefitinib); and NCT02148380 (gefitinib +chemotherapy vs. gefitinib vs. chemotherapy) trials. Cost-related data were obtained from hospitals and published literature. The effect parameter (quality-adjusted life year [QALY]) was the reflection of both survival and utility. Incremental cost-effectiveness ratio (ICER), average cost-effectiveness ratio (ACER), and net benefit were calculated, and the willingness-to-pay (WTP) threshold was set at $30828/QALY from the perspective of the Chinese healthcare system. Sensitivity analysis was performed to explore the stability of results. RESULTS: We compared treatment groups with control groups in each trial. ICERs were $1897750.74/QALY (ARCHER1050), $416560.02/QALY (FLAURA), -$477607.48/QALY (JO25567), -$464326.66/QALY (NEJ026), -$277121.22/QALY (NEJ009), -$399360.94/QALY (gefitinib as comparison, NCT02148380), and -$170733.05/QALY (chemotherapy as comparison, NCT02148380). Moreover, ACER and net benefit showed that the combination of EGFR-TKI with chemotherapy and osimertinib was of more economic benefit following first-generation EGFR-TKIs. Sensitivity analyses showed that the impact of utilities and monotherapy could be cost-effective with a 50% cost reduction. CONCLUSION: First-generation EGFR-TKI therapy remained the most cost-effective treatment option for advanced EGFR-mutant NSCLC patients. Our results could serve as both a reference for both clinical practice and the formulation of medical insurance reimbursement.
Subject(s)
Antineoplastic Agents/economics , Carcinoma, Non-Small-Cell Lung/drug therapy , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Mutation , Protein Kinase Inhibitors/economics , Acrylamides/economics , Acrylamides/therapeutic use , Angiogenesis Inhibitors/economics , Angiogenesis Inhibitors/therapeutic use , Aniline Compounds/economics , Aniline Compounds/therapeutic use , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/economics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/economics , Bevacizumab/therapeutic use , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/mortality , China , Clinical Trials as Topic/economics , Cost-Benefit Analysis , ErbB Receptors/antagonists & inhibitors , Erlotinib Hydrochloride/economics , Erlotinib Hydrochloride/therapeutic use , Gefitinib/economics , Gefitinib/therapeutic use , Humans , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Markov Chains , Protein Kinase Inhibitors/therapeutic use , Quality-Adjusted Life Years , Quinazolinones/economics , Quinazolinones/therapeutic useABSTRACT
PURPOSE: To perform a societal cost-benefit analysis comparing intravitreal bevacizumab (Avastin), ranibizumab (Lucentis), and aflibercept (Eylea) monotherapies for treating neovascular age-related macular degeneration (NVAMD). DESIGN: Cost-benefit analysis. METHODS: Center for Value-Based Medicine using published clinical trial and Medicare data. PATIENT POPULATION: 168,400 estimated 2018 U.S. patients with new-onset NVAMD. Procedure(s): cost-benefit analysis using 2018 U.S. real dollars. OUTCOME MEASUREMENTS: 11-year direct ophthalmic medical costs expended for bevacizumab, ranibizumab, and aflibercept monotherapies were compared with ophthalmic and nonophthalmic direct medical, direct nonmedical, and indirect medical (productivity) costs saved by the therapies. RESULTS: Bevacizumab monotherapy had an individual, 11-year $14,772 treatment cost and net $357,680 societal return (11-year 2,421% return on investment [ROI]). Ranibizumab therapy cost $106,582 and returned $265,870 to society (249% ROI), whereas aflibercept treatment cost $61,811 and returned $310,611 to society (503% ROI). The 2018 NVAMD overall treatment cohort, 11-year net societal gain was $28.5 billion to patients and insurers, with $24.2 billion (84.9%) coming from bevacizumab therapy, $0.7 billion (2.5%) from ranibizumab therapy, and $3.6 billion (12.6%) from aflibercept therapy. Substituting bevacizumab for ranibizumab and aflibercept in the 2018 new-onset NVAMD patients would save an estimated $1.343 billion over 11 years. Vascular endothelial growth factor-inhibitor (VEGF-I) therapy in 2018 should contribute $12.2 billion to the Gross Domestic Product over 11 years. Late treatment would decrease this by 78% to $2.7 billion. CONCLUSIONS: Intravitreal NVAMD bevacizumab, ranibizumab and aflibercept monotherapies accrue considerable financial, ROIs to patients and insurers as they increase national wealth.
Subject(s)
Angiogenesis Inhibitors/economics , Drug Costs , Quality-Adjusted Life Years , Visual Acuity , Wet Macular Degeneration/drug therapy , Aged , Aged, 80 and over , Angiogenesis Inhibitors/administration & dosage , Cost-Benefit Analysis , Female , Humans , Incidence , Intravitreal Injections , Male , United States/epidemiology , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Wet Macular Degeneration/economics , Wet Macular Degeneration/epidemiologyABSTRACT
PURPOSE: To evaluate the cost-utility of treatment for macular edema in central retinal vein occlusion (CRVO) using intravitreal injections of the anti-vascular endothelial growth factor (VEGF) agents bevacizumab, ranibizumab, and aflibercept. DESIGN: Decision analysis model of cost-utility. PARTICIPANTS: Data from study participants in the Lucentis, Eylea, Avastin in Vein Occlusion (LEAVO) study. METHODS: A decision analysis of a disease simulation model was used to calculate comparative cost-utility of intravitreal bevacizumab (IVB), intravitreal ranibizumab (IVR), and intravitreal aflibercept (IVA) for the treatment of macular edema associated with CRVO based on data from the LEAVO study. Center for Medicare and Medicaid Services data were used to calculate associated modeled costs in a hospital- or facility-based and nonfacility setting from a third-party payer perspective, and societal costs also were calculated. Cost utility was calculated based on the preserved visual utility during the 2 years of the study and also by estimating utility for the expected lifetime. MAIN OUTCOME MEASURES: Cost of treatment, cost per quality-adjusted life-year (QALY), and incremental cost-effectiveness ratio (ICER). RESULTS: From the third-party payer perspective, the estimated lifetime costs per QALY in the facility and nonfacility settings were $39 325 and $17 944, respectively, for IVB; $114 095 and $92 653, respectively, for IVR; and $78 935 and $63 270, respectively, for IVA. From the societal perspective, the estimated lifetime costs per QALY in the facility setting were $52 754 for IVB, $128 242 for IVR, and $86 262 for IVA. The ICER of IVA compared with that of IVB was $153 633/QALY from the third-party facility setting and $152 992/QALY from the societal perspective. The use of IVB compared with IVR and IVA compared with IVR were cost-saving interventions (ICER, <0) regardless of the perspective or setting. CONCLUSIONS: In the treatment of macular edema in CRVO, IVB yields the best cost utility among the 3 anti-VEGF agents modeled. Intravitreal aflibercept maintains acceptable lifetime cost per QALY while having a favorable cost utility compared with IVR.
Subject(s)
Angiogenesis Inhibitors/economics , Drug Costs , Macular Edema/drug therapy , Medicare/economics , Retinal Vein Occlusion/drug therapy , Visual Acuity , Angiogenesis Inhibitors/administration & dosage , Cost-Benefit Analysis , Fluorescein Angiography , Follow-Up Studies , Fundus Oculi , Humans , Intravitreal Injections , Macular Edema/economics , Macular Edema/etiology , Prospective Studies , Retinal Vein Occlusion/complications , Retinal Vein Occlusion/economics , Tomography, Optical Coherence , United States , Vascular Endothelial Growth Factors/antagonists & inhibitorsABSTRACT
The use of poly (ADP-ribose) polymerase (PARP) inhibitors in the front-line management of advanced ovarian cancer has recently emerged as an exciting strategy with the potential to improve outcomes for patients with advanced ovarian cancer. In this article, we review the results of four recently published Phase III randomised controlled trials evaluating the use of PARP inhibitors in the primary treatment of ovarian cancer (SOLO1, PRIMA, PAOLA-1, and VELIA). Collectively, the studies suggest that PARP maintenance in the upfront setting is most beneficial among patients with BRCA-associated ovarian cancers (hazard ratios range from 0.31 to 0.44), followed by patients with tumours that harbour homologous recombination deficiencies (hazard ratios range from 0.33 to 0.57). All three studies that included an all-comer population were able to demonstrate benefit of PARP inhibitors, regardless of biomarker status. The FDA has approved olaparib for front-line maintenance therapy among patients with BRCA-associated ovarian cancers, and niraparib for all patients, regardless of biomarker status. In determining which patients should be offered front-line maintenance PARP inhibitors, and which agent to use, there are multiple factors to consider, including FDA indication, dosing preference, toxicity, risks versus benefits for each patient population, and cost. There are ongoing studies further exploring the front-line use of PARP inhibitors, including the potential downstream effects of PARP-inhibitor resistance in the recurrent setting, combining PARP-inhibitors with other anti-angiogenic drugs, immunotherapeutic agents, and inhibitors of pathways implicated in PARP inhibitor resistance.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Ovarian Neoplasms/drug therapy , Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage , Poly(ADP-ribose) Polymerases/metabolism , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/adverse effects , Angiogenesis Inhibitors/economics , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/economics , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/economics , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Clinical Trials, Phase III as Topic , Cost-Benefit Analysis , Drug Approval , Drug Costs , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/genetics , Female , Humans , Indazoles/administration & dosage , Indazoles/adverse effects , Indazoles/economics , Maintenance Chemotherapy/methods , Mutation , Ovarian Neoplasms/economics , Ovarian Neoplasms/genetics , Ovarian Neoplasms/mortality , Phthalazines/administration & dosage , Phthalazines/adverse effects , Phthalazines/economics , Piperazines/administration & dosage , Piperazines/adverse effects , Piperazines/economics , Piperidines/administration & dosage , Piperidines/adverse effects , Piperidines/economics , Poly(ADP-ribose) Polymerase Inhibitors/adverse effects , Poly(ADP-ribose) Polymerase Inhibitors/economics , Progression-Free Survival , Randomized Controlled Trials as Topic , Recombinational DNA Repair/drug effects , United States , United States Food and Drug Administration/legislation & jurisprudenceABSTRACT
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.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Choroidal Neovascularization/drug therapy , Cost-Benefit Analysis , Physical Examination/economics , Tomography, Optical Coherence/economics , Visual Acuity , Wet Macular Degeneration/drug therapy , Aged , Angiogenesis Inhibitors/economics , Bevacizumab/economics , Bevacizumab/therapeutic use , Choroidal Neovascularization/economics , Cost Savings/economics , Female , Humans , Intravitreal Injections , Male , Middle Aged , Mydriatics/administration & dosage , Pupil/drug effects , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/economics , Recombinant Fusion Proteins/therapeutic use , Retreatment , Treatment Outcome , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Wet Macular Degeneration/economicsABSTRACT
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.
Subject(s)
Angiogenesis Inhibitors/economics , Cost Savings/economics , Fee-for-Service Plans/economics , Medicare Part B/economics , Bevacizumab/economics , Health Expenditures , Intravitreal Injections , Ranibizumab/economics , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins/economics , Registries , United States , Vascular Endothelial Growth Factor A/antagonists & inhibitorsABSTRACT
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.
Subject(s)
Angiogenesis Inhibitors/economics , Choroidal Neovascularization/economics , Cost-Benefit Analysis , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Vascular Endothelial Growth Factor A/economics , Wet Macular Degeneration/economics , Aged , Angiogenesis Inhibitors/therapeutic use , Bevacizumab/economics , Bevacizumab/therapeutic use , Choroidal Neovascularization/drug therapy , Drug Costs , Female , Health Care Costs , Humans , Intravitreal Injections , Male , Medicare , Quality-Adjusted Life Years , Ranibizumab/economics , Ranibizumab/therapeutic use , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/economics , Recombinant Fusion Proteins/therapeutic use , United States , Visual Acuity , Wet Macular Degeneration/drug therapyABSTRACT
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.