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1.
Adv Ther ; 33(1): 116-28, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26747252

ABSTRACT

INTRODUCTION: Ranibizumab and aflibercept are anti-vascular endothelial growth factor agents licensed for the treatment of visual impairment due to macular edema secondary to branch retinal vein occlusion (BRVO). The aim of this study was to estimate, from a UK healthcare payer's perspective, the cost-effectiveness of ranibizumab versus aflibercept in this indication. METHODS: A Markov model was used to simulate the outcomes and costs of treating BRVO. Patient baseline characteristics and efficacy data for ranibizumab were obtained from the BRAVO trial. The relative efficacy of aflibercept was derived from a published network meta-analysis. Injection frequencies were derived from ranibizumab and aflibercept studies included in the network meta-analysis. Health states were defined by increments of 10 letters in best corrected visual acuity (BCVA). Patients could gain or lose a maximum of two health states between cycles. The first cycle was 6 months, followed by monthly cycles. Different utility values were assigned to the better-seeing and worse-seeing eyes based on BCVA. A 2-year treatment time frame and a lifetime time horizon were used. Future costs and health outcomes were discounted at 3.5% per annum. Sensitivity analyses were used to test the robustness of the model. RESULTS: The lifetime cost per patient treated was £15,273 with ranibizumab and £17,347 with aflibercept. Ranibizumab was dominant over aflibercept, producing incremental health gains of 0.0120 quality-adjusted life-years (QALYs) and cost savings of £2074. Net monetary benefit for ranibizumab at a willingness-to-pay threshold of £20,000/QALY was £2314. Sensitivity analyses showed that the results were robust to variations in model parameters. CONCLUSIONS: Ranibizumab provides greater health gains at a lower overall cost than aflibercept in the treatment of visual impairment due to macular edema secondary to BRVO. Ranibizumab is therefore cost-effective from a UK healthcare payer's perspective. FUNDING: Novartis Pharma AG, Basel, Switzerland.


Subject(s)
Macular Edema/drug therapy , Ranibizumab/economics , Ranibizumab/therapeutic use , Receptors, Vascular Endothelial Growth Factor/economics , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/economics , Recombinant Fusion Proteins/therapeutic use , Cost-Benefit Analysis , Female , Humans , Macular Edema/etiology , Male , Quality-Adjusted Life Years , Retinal Vein Occlusion/complications , Switzerland , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visual Acuity
2.
JAMA Ophthalmol ; 134(1): 95-9, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26512939

ABSTRACT

IMPORTANCE: The Diabetic Retinopathy Clinical Research Network (DRCR Network), sponsored by the National Eye Institute, reported the results of a comparative effectiveness randomized clinical trial (RCT) evaluating the 3 anti-vascular endothelial growth factor (anti-VEGF) agents aflibercept (2.0 mg), bevacizumab (1.25 mg), and ranibizumab (0.3 mg) for treatment of diabetic macular edema (DME) involving the center of the retina and associated with visual acuity loss. The many important findings of the RCT prompted the American Society of Retina Specialists to convene a group of experts to provide their perspective regarding clinically relevant findings of the study. OBJECTIVES: To describe specific outcomes of the RCT judged worthy of highlighting, to discuss how these and other clinically relevant results should be considered by specialists treating DME, and to identify unanswered questions that merit consideration before treatment. EVIDENCE REVIEW: The DRCR Network-authored publication on primary outcomes of the comparative effectiveness RCT at 89 sites in the United States. The study period of the RCT was August 22, 2012, to August 28, 2013. FINDINGS: On average, all 3 anti-VEGF agents led to improved visual acuity in eyes with DME involving the center of the retina and with visual acuity impairment, including mean (SD) improvements by +13.3 (11.1) letters with aflibercept vs +9.7 (10.1) letters with bevacizumab (P < .001) and +11.2 (9.4) letters with ranibizumab (P = .03). Worse visual acuity when initiating therapy was associated with greater visual acuity benefit of aflibercept (+18.9 [11.5]) over bevacizumab (+11.8 [12.0]) or ranibizumab (14.2 [10.6]) 1 year later (P < .001 for interaction with visual acuity as a continuous variable, and P = .002 for interaction with visual acuity as a categorical variable). It is unknown whether different visual acuity outcomes associated with the use of the 3 anti-VEGF agents would be noted with other treatment regimens or with adequately repackaged bevacizumab, as well as in patients with criteria that excluded them from the RCT, such as persistent DME despite recent anti-VEGF treatment. CONCLUSIONS AND RELEVANCE: On average, all 3 anti-VEGF agents led to improved visual acuity in eyes with DME involving the center of the retina and visual acuity impairment. Worse visual acuity when initiating therapy was associated with greater visual acuity benefit of aflibercept over bevacizumab or ranibizumab 1 year later. Care needs to be taken when attempting to extrapolate outcomes of this RCT to differing treatment regimens. With access to adequately repackaged bevacizumab, many specialists might initiate therapy with bevacizumab when visual acuity is good (ie, 20/32 to 20/40 as measured in the DRCR Network), recognizing that the cost-effectiveness of bevacizumab outweighs that of aflibercept or ranibizumab.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Bevacizumab/therapeutic use , Diabetic Retinopathy/drug therapy , Macular Edema/drug therapy , Ranibizumab/therapeutic use , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Angiogenesis Inhibitors/economics , Bevacizumab/economics , Cost-Benefit Analysis , Diabetic Retinopathy/physiopathology , Drug Compounding , Drug Costs , Humans , Intravitreal Injections , Macular Edema/physiopathology , Practice Guidelines as Topic , Practice Patterns, Physicians' , Randomized Controlled Trials as Topic , Ranibizumab/economics , Receptors, Vascular Endothelial Growth Factor/economics , Recombinant Fusion Proteins/economics , Treatment Outcome , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visual Acuity/drug effects
3.
PLoS One ; 10(8): e0135050, 2015.
Article in English | MEDLINE | ID: mdl-26241852

ABSTRACT

BACKGROUND: Treatment efficacy and costs of anti-VEGF drugs have not been studied in clinical routine. OBJECTIVE: To compare treatment costs and clinical outcomes of the medications when adjusting for patients' characteristics and clinical status. DESIGN: Comparative study. SETTING: The largest public ophthalmologic clinic in Switzerland. PATIENTS: Health care claims data of patients with age-related macular degeneration, diabetic macula edema and retinal vein occlusion were matched to clinical and outcome data. MEASUREMENTS: Patients' underlying condition, gender, age, visual acuity and retinal thickness at baseline and after completing the loading phase, the total number of injections per treatment, the visual outcome and vital status was secured. RESULTS: We included 315 patients (19595 claims) with a follow-up time of 1 to 99 months (mean 32.7, SD 25.8) covering the years 2006-2014. Mean age was 78 years (SD 9.3) and 200 (63.5%) were female. At baseline, the mean number of letters was 55.6 (SD 16.3) and the central retinal thickness was 400.1 µm (SD 110.1). Patients received a mean number of 15.1 injections (SD 13.7; range 1 to 85). Compared to AMD, adjusted cost per month were significantly higher (+2174.88 CHF, 95%CI: 1094.50-3255.27; p<0.001) for patients with DME, while cost per month for RVO were slightly but not significantly higher. (+284.71 CHF, 95% CI: -866.73-1436.15; p = 0.627). CONCLUSIONS: Patients with DME are almost twice as expensive as AMD and RVO patients. Cost excess occurs with non-ophthalmologic interventions. The currently licensed anti-VEGF medications did not differ in costs, injection frequency and clinical outcomes. Linking health care claims to clinical data is a useful tool to examine routine clinical care.


Subject(s)
Diabetic Retinopathy/drug therapy , Macular Degeneration/drug therapy , Macular Edema/drug therapy , Ranibizumab/therapeutic use , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Retinal Vein Occlusion/drug therapy , Aged , Ambulatory Care Facilities/statistics & numerical data , Costs and Cost Analysis , Diabetic Retinopathy/economics , Female , Health Care Costs/statistics & numerical data , Humans , Insurance Claim Review , Macular Degeneration/economics , Macular Edema/economics , Male , Ranibizumab/economics , Receptors, Vascular Endothelial Growth Factor/economics , Recombinant Fusion Proteins/economics , Retinal Vein Occlusion/economics , Tomography, Optical Coherence , Treatment Outcome , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visual Acuity
5.
J Fr Ophtalmol ; 38(7): 573-9, 2015 Sep.
Article in French | MEDLINE | ID: mdl-25997681

ABSTRACT

INTRODUCTION: Two or three systematic intravitreal injections (IVT) may be prescribed in a PRN approach to treat an exudative recurrence of neovascular age-related macular degeneration (AMD), according to the phenotype. Optical coherence tomography (OCT) may be performed immediately before the 2nd or the 3rd scheduled IVT, making it possible to cancel the procedure in the absence of exudation. The aim of the study was to evaluate the usefulness of this OCT examination and to assess the percentage of IVT cancelled, in order to evaluate a potential medico-economic benefit. METHODS: Monocentric retrospective study, in which were included 292 consecutive eyes with exudative recurrence of AMD, for which 2 or 3 IVT were scheduled between January 1st and April 30th, 2014. All patients received a first systematic IVT in the seven days following the diagnosis. Then, on the days of the 2nd and 3rd scheduled IVT, each patient had a visual acuity measurement and a Spectral domain-OCT (Spectralis, HRA Heidelberg Engineering). This measurement allowed for the IVT to be either performed as scheduled or cancelled. Both ranibizumab and aflibercept were used. A Chi(2) test was used to compare the qualitative variables and an adjusted Wilcoxon test for the quantitative values. RESULTS: Two hundred and ninety-two consecutive eyes were included; 172 in the "2 scheduled IVT" group (group A) and 120 in the "3 scheduled IVT" group (group B). At the first follow-up, 37.6% of scheduled IVT were cancelled after the OCT (44.1% in group A and 28.3% in group B). At the second follow-up, 33.3% of IVT were cancelled in group B. Overall, 150/412 (36.4%) IVT were avoided in this series. Presence of serous retinal detachment, retinal edema and increased central macular thickness were statistically correlated with confirmation of the scheduled IVT at the two follow-ups (P<0.001, P<0.001 and P=0.002, respectively). A savings of 429.80 € per patient was calculated during this short period of follow-up. CONCLUSION: An average non-injection rate of 36.4% of scheduled IVT was found in this protocol of management of recurrences with OCT performed the day of IVT. This protocol allowed to avoid unnecessary IVT one-third of the time and appeared highly cost-effective.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Ranibizumab/therapeutic use , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Tomography, Optical Coherence/methods , Unnecessary Procedures , Wet Macular Degeneration/pathology , Aged , Aged, 80 and over , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/economics , Cost Savings , Cost-Benefit Analysis , Disease Management , Exudates and Transudates , Female , Humans , Intravitreal Injections , Male , Middle Aged , Papilledema/diagnosis , Papilledema/etiology , Ranibizumab/administration & dosage , Ranibizumab/economics , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Receptors, Vascular Endothelial Growth Factor/economics , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/economics , Recurrence , Retinal Detachment/diagnosis , Retinal Detachment/etiology , Retrospective Studies , Tomography, Optical Coherence/economics , Unnecessary Procedures/economics , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visual Acuity , Wet Macular Degeneration/complications , Wet Macular Degeneration/drug therapy , Wet Macular Degeneration/economics
6.
Br J Ophthalmol ; 99(8): 1055-9, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25677668

ABSTRACT

BACKGROUND/AIMS: Aflibercept is an approved therapy for neovascular age-related macular degeneration (AMD) and diabetic macular oedema (DME). In vitro and in vivo studies did not detect toxicity to the retinal pigment epithelium cells using the approved cancer protein, ziv-aflibercept. Our purpose is to determine if ziv-aflibercept can be used in AMD and DME without ocular toxicity, to test the stability of ziv-aflibercept, and to do a cost analysis. METHODS: Prospectively, consecutive patients with AMD or DME and poor vision underwent one intravitreal injection of 0.05 mL of fresh filtered ziv-aflibercept (1.25 mg). Monitoring of best-corrected visual acuity, intraocular inflammation, cataract progression, and retinal structure by spectral domain optical coherence tomography was done at 1 day and 1 week after injection. Ziv-aflibercept activity over 4 weeks was measured by capturing vascular endothelial growth factor by ELISA. RESULTS: There were no signs of retinal toxicity, intraocular inflammation or change in lens status in four eyes with AMD and two eyes with DME. Visual acuity improved (p=0.05) and central foveal thickness decreased in all patients (p=0.05). Ziv-aflibercept had no loss of anti-VEGF activity when kept at 4°C in polycarbonate syringes over 4 weeks. Similar to bevacizumab, compounded ziv-aflibercept would yield a tremendous saving compared with aflibercept or ranibizumab. CONCLUSIONS: Off-label use of ziv-aflibercept improves visual acuity without ocular toxicity and may offer a cheaper alternative to the same molecule aflibercept. TRIAL REGISTRATION NUMBER: NCT02173873.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Diabetic Retinopathy/drug therapy , Macular Edema/drug therapy , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Wet Macular Degeneration/drug therapy , Aged , Aged, 80 and over , Angiogenesis Inhibitors/economics , Cost-Benefit Analysis , Diabetic Retinopathy/economics , Diabetic Retinopathy/physiopathology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Intravitreal Injections , Macular Edema/economics , Macular Edema/physiopathology , Male , Middle Aged , Off-Label Use , Prospective Studies , Receptors, Vascular Endothelial Growth Factor/economics , Recombinant Fusion Proteins/economics , Subretinal Fluid , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visual Acuity/physiology , Wet Macular Degeneration/economics , Wet Macular Degeneration/physiopathology
7.
Article in English | MEDLINE | ID: mdl-25559511

ABSTRACT

BACKGROUND AND OBJECTIVE: To test the hypothesis that although intravitreal aflibercept (IVA) is expected to be more expensive, the extra cost of treatment would not result in additional vision gain compared with intravitreal bevacizumab (IVB) for the treatment of wet age-related macular degeneration (AMD). PATIENTS AND METHODS: A retrospective chart review of patients receiving IVB or intravitreal ranibizumab (IVR) who were subsequently changed to IVA for active wet AMD. RESULTS: Thirty-three eyes were included in the study. The mean number of IVB, IVR, and IVA injections per eye over a 6-month period was seven, six, and five, respectively. Visual outcomes were similar in all three groups at the end of the study period. The average drug cost of IVB, IVR, and IVA injections per eye over 6 months was $326, $11,400, and $9,720, respectively. CONCLUSION: Aflibercept may allow a modest extension of the treatment interval, but cost makes IVA an expensive alternative without a visual benefit compared with IVB in patients with active wet AMD.


Subject(s)
Angiogenesis Inhibitors/economics , Antibodies, Monoclonal, Humanized/economics , Cost-Benefit Analysis , Receptors, Vascular Endothelial Growth Factor/economics , Recombinant Fusion Proteins/economics , Wet Macular Degeneration/economics , Aged , Aged, 80 and over , Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Bevacizumab , Drug Costs , Drug Substitution , Female , Fluorescein Angiography , Humans , Intravitreal Injections , Male , Ranibizumab , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Retrospective Studies , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visual Acuity/physiology , Wet Macular Degeneration/drug therapy , Wet Macular Degeneration/physiopathology
8.
Pharmacoeconomics ; 33(5): 457-66, 2015 May.
Article in English | MEDLINE | ID: mdl-25616671

ABSTRACT

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of aflibercept (Sanofi) to submit clinical and cost-effectiveness evidence for aflibercept in combination with irinotecan and fluorouracil-based therapy [irinotecan/5-fluorouracil/folinic acid (FOLFIRI)] for the treatment of metastatic colorectal cancer which has progressed following prior oxaliplatin-based chemotherapy, as part of the Institute's Single Technology Appraisal process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and the resulting NICE guidance TA307 issued in March 2014. The ERG critically reviewed the evidence presented in the manufacturer's submission and identified areas requiring clarification, for which the manufacturer provided additional evidence. The clinical effectiveness data were derived from one good-quality double-blind randomised controlled trial (RCT), the VELOUR trial, which compared aflibercept plus FOLFIRI with placebo plus FOLFIRI. This RCT found a small but statistically significant increase in overall survival (OS); the difference in median OS was 1.44 months (13.5 months in the aflibercept group and 12.06 months in the placebo group). There was also a statistically significant increase in progression-free survival (PFS) with aflibercept; the difference in median PFS was 2.23 months (6.9 months in the aflibercept group and 4.67 months in the placebo group). However, grade 3-4 adverse events were more frequent in the aflibercept group than the placebo group: 83.5% compared with 62.5%. Treatment-emergent adverse events led to permanent discontinuation of treatment in 26.8% of patients in the aflibercept group and 12.1% of patients in the placebo group. The manufacturer's submission included an estimation of mean OS benefit based on extrapolation of the data, which was considerably longer than the median OS benefit reported (4.7 vs. 1.44 months). The ERG considered this to be an over estimate. The base-case incremental cost-effectiveness ratio (ICER) for the overall population was reported by the manufacturer to be £36,294 per quality-adjusted life-year (QALY). After correcting the model programming and updating the model to include the ERG's preferred parameter estimates, the ICER from the ERG's alternative base case was £54,368 per QALY. The extrapolation of the OS curves was the key cost-effectiveness driver and a major source of uncertainty in the model. Additional scenarios related to the extrapolation of OS undertaken by the ERG resulted in ICERs between £62,894 and £92,089 per QALY. After consideration of the manufacturer's submission and the ERG's critique, and submissions from other stakeholders, the NICE Appraisal Committee concluded that aflibercept in combination with irinotecan and fluorouracil-based therapy could not be considered a cost effective use of National Health Service resources for treating metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin-containing regimen. Aflibercept in combination with irinotecan and fluorouracil-based therapy is not recommended for the treatment of metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin-containing regimen in NICE guidance TA307.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/economics , Camptothecin/analogs & derivatives , Colorectal Neoplasms/drug therapy , Cost-Benefit Analysis , Organoplatinum Compounds/therapeutic use , Receptors, Vascular Endothelial Growth Factor/economics , Recombinant Fusion Proteins/economics , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/administration & dosage , Camptothecin/adverse effects , Camptothecin/economics , Camptothecin/therapeutic use , Colorectal Neoplasms/economics , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Disease Progression , Disease-Free Survival , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Fluorouracil/economics , Fluorouracil/therapeutic use , Health Care Costs/statistics & numerical data , Humans , Kaplan-Meier Estimate , Leucovorin/administration & dosage , Leucovorin/adverse effects , Leucovorin/economics , Leucovorin/therapeutic use , Models, Economic , Neoplasm Metastasis , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Oxaliplatin , Quality-Adjusted Life Years , Randomized Controlled Trials as Topic , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Receptors, Vascular Endothelial Growth Factor/adverse effects , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/adverse effects , Recombinant Fusion Proteins/therapeutic use
9.
Pol Merkur Lekarski ; 37(217): 56-60, 2014 Jul.
Article in Polish | MEDLINE | ID: mdl-25154202

ABSTRACT

Currently in Poland neovascular form of age-related macular degeneration (AMD) is treated with vascular endothelial growth factor (VEGF) inhibitors--ranibizumab, aflibercept and bevacizumab. Photodynamic therapy is still refunded, although it is very rarely used. It can be estimated that only small minority (about 5-10%) of cases are properly treated due to mainly refunding restrictions in Poland. In countries with wider access to treatment 50% reduction in AMD-related blindness incidence was noted. Low-cost off-label anti-VEGF agent bevacizumab is almost inaccessible in Polish public health system because of law regulations. In order to increase availability of anti-VEGF injections vials of all mentioned drugs are divided which raises safety concerns. Despite new potent drug in the market aflibercept, cost of treatment remains very high. The optimal treatment regimen includes three monthly injections, after which is usually used pro re nata therapy based primarily on the outcome of macular optical coherence tomography. Routinely recommended antibiotic prophylaxis of injection-related endophthalmitis probably has no meaning apart from the generation of resistance.


Subject(s)
Macular Degeneration/drug therapy , Neovascularization, Pathologic/drug therapy , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/economics , Bevacizumab , Drug Administration Schedule , Humans , Neovascularization, Pathologic/etiology , Photochemotherapy/economics , Poland , Ranibizumab , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Receptors, Vascular Endothelial Growth Factor/economics , Receptors, Vascular Endothelial Growth Factor/supply & distribution , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/economics , Recombinant Fusion Proteins/supply & distribution , Reimbursement, Incentive
10.
Farm Hosp ; 38(4): 317-27, 2014 Jul 01.
Article in Spanish | MEDLINE | ID: mdl-25137165

ABSTRACT

OBJECTIVES: To estimate the incremental cost per life-year gained (LYG) of aflibercept in combination with FOLFIRI as second-line treatment in metastatic colorectal cancer (mCRC) patients previously treated with oxaliplatin. METHODS: Based on clinical trial VELOUR results, a three-state Markov model (stable disease, progression and death) with 2-week cycle duration was designed. Transition to health state «progression¼ implied the interruption of second-line treatment and administration of a third-line treatment (post-second line chemotherapy). Cost estimation included disease management cost (pharmaceutical, adverse event management, administration costs, etc.). Both cost and outcomes were discounted (3% annually). Sensitivity analyses (SA) were performed to test model robustness. RESULTS: Administration of aflibercept + FOLFIRI as second-line treatment provided 1.78 LYG (21 life-months gained). With FOLFIRI 1.43 LYG (17 months) were obtained. The cost of the clinical management of aflibercept + FOLFIRI implied an additional investment of Euros 13,564 compared with FOLFIRI for a lifetime horizon, being total costs for aflibercept + FOLFIRI of Euros 38,346, compared to Euros 24,782 with FOLFIRI. In the cost-effectiveness analysis Euros 38,931/LYG was obtained with aflibercept in combination with FOLFIRI versus FOLFIRI. CONCLUSION: Aflibercept in combination with FOLFIRI increased overall survival versus FOLFIRI, so it is an effective strategy in the treatment of patients with mCRC. Aflibercept in combination with FOLFIRI is an efficient strategy for second-line mCRC treatment from the National Health System perspective.


OBJETIVOS: Estimar el coste incremental por año de vida ganado (AVG) de la utilización de aflibercept en combinación con FOLFIRI como tratamiento de 2ª línea en pacientes con cáncer colorrectal metastásico (CCRm) previamente tratados con oxaliplatino. MATERIAL Y MÉTODOS: Basándose en los resultados del ensayo clínico VELOUR, se utilizó un modelo de Markov con 3 estados de salud (enfermedad estable, progresión y muerte) y ciclos de 2 semanas. La transición al estado de salud «progresión¼ implicaba interrumpir el tratamiento en 2ª línea y administrar una 3ª línea de tratamiento. La estimación de costes incluyó costes del manejo de la enfermedad (farmacológicos, acontecimientos adversos, administración, etc.). Costes y resultados en salud fueron descontados al 3% anualmente. Para probar la robustez del modelo se realizaron análisis de sensibilidad determinístico y probabilístico. RESULTADOS: La administración de aflibercept + FOLFIRI como 2ª línea de quimioterapia aporta 1,78 AVG (21 meses de vida ganados). Con FOLFIRI se consiguen 1,43 AVG (17 meses). El coste del manejo clínico de aflibercept + FOLFIRI supone una inversión adicional de 13.564 frente a FOLFIRI a lo largo de toda la vida del paciente, siendo el coste total de 38.346 para aflibercept + FOLFIRI y 24.782 para FOLFIRI. Se obtiene un RCEI (ratio coste efectividad incremental) de 38.931 /AVG con aflibercept + FOLFIRI frente a FOLFIRI. CONCLUSIÓN: Aflibercept en combinación con FOLFIRI incrementa la supervivencia global frente a FOLFIRI, lo que supone una estrategia efectiva en el tratamiento de pacientes con CCRm. La relación coste-efectividad incremental de aflibercept en combinación con FOLFIRI supone una estrategia eficiente, coste-efectiva, para el Sistema Nacional de Salud.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/economics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/analogs & derivatives , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/economics , Cost-Benefit Analysis , Receptors, Vascular Endothelial Growth Factor/economics , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/economics , Recombinant Fusion Proteins/therapeutic use , Camptothecin/economics , Camptothecin/therapeutic use , Colorectal Neoplasms/pathology , Drug Therapy, Combination , Fluorouracil/economics , Fluorouracil/therapeutic use , Humans , Leucovorin/economics , Leucovorin/therapeutic use , Markov Chains , Neoplasm Metastasis
13.
Graefes Arch Clin Exp Ophthalmol ; 252(12): 1911-20, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24777708

ABSTRACT

BACKGROUND: Age-related macular degeneration (AMD) is a blinding disease placing considerable burden on society due to blindness-associated costs. Intravitreal anti-vascular endothelial growth factors (anti-VEGFs) are effective in reducing the incidence of blindness, but at potentially high costs, depending on the cost of the drug used. Aflibercept has been introduced as an anti-VEGF equally effective to ranibizumab, but less costly. For this new drug, new cost-effectiveness analyses are needed, and AMD models used today give biased results. We investigated the cost-effectiveness of aflibercept compared to bevacizumab, ranibizumab, and no treatment and studied the influence of commonly used model parameters. METHODS: A patient-level, visual acuity-based, 2-eye model was developed. Data on effectiveness were derived from randomized controlled trials evaluating the outcomes of aflibercept, bevacizumab, and ranibizumab. Utility and resource utilization were assessed in interviews with AMD patients. Costs were based on standard health care cost prices. Time horizons were two and five years. A societal perspective was employed. RESULTS: Over five years, costs associated with aflibercept treatment were 36,030, with 2.15 QALYs. Costs associated with the bevacizumab regimens, ABC study as-needed (PRN); CATT study PRN; and CATT study 1×/month, were 19,367; 26,746; and 30,520, with 2.16; 2.17; and 2.15 QALYs, respectively. Costs associated with ranibizumab PRN and 1×/month were 45,491 and 74,837 with 2.16 and 2.15 QALYs, respectively. 'No treatment' was associated with 9530 and 1.96 QALYs. The incremental cost-effectiveness ratios versus 'no treatment' were: aflibercept-140,274; bevacizumab-51,062 (ABC PRN), 83,256 (CATT PRN) and 110,361 (1×/month); ranibizumab-181,667 (PRN) and 349,773 (1×/month). Results were highly dependent on whether only one or both eyes were included, length of time horizon, and whether the costs of blindness and low-vision were included in the analysis. CONCLUSIONS: Aflibercept is a cost-effective treatment for AMD over ranibizumab. However, aflibercept is not a cost-effective treatment when compared to bevacizumab. Application of inappropriate model assumptions leads to a biased cost-saving estimate of the cost-effectiveness of aflibercept. Therefore, cost-effectiveness analyses should be conducted with appropriate models.


Subject(s)
Angiogenesis Inhibitors/economics , Antibodies, Monoclonal, Humanized/economics , Cost-Benefit Analysis , Macular Degeneration/economics , Receptors, Vascular Endothelial Growth Factor/economics , Recombinant Fusion Proteins/economics , Aged , Aged, 80 and over , Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Bevacizumab , Drug Costs , Female , Health Care Costs , Humans , Intravitreal Injections , Macular Degeneration/drug therapy , Male , Middle Aged , Models, Economic , Monte Carlo Method , Quality-Adjusted Life Years , Ranibizumab , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Visual Acuity/physiology
14.
Ann Intern Med ; 160(1): 18-29, 2014 Jan 07.
Article in English | MEDLINE | ID: mdl-24573663

ABSTRACT

BACKGROUND: Macular edema is the most common cause of vision loss among patients with diabetes. OBJECTIVE: To determine the cost-effectiveness of different treatments of diabetic macular edema (DME). DESIGN: Markov model. DATA SOURCES: Published literature and expert opinion. TARGET POPULATION: Patients with clinically significant DME. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Laser treatment, intraocular injections of triamcinolone or a vascular endothelial growth factor (VEGF) inhibitor, or a combination of both. OUTCOME MEASURES: Discounted costs, gains in quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: All treatments except laser monotherapy substantially reduced costs, and all treatments except triamcinolone monotherapy increased QALYs. Laser treatment plus a VEGF inhibitor achieved the greatest benefit, gaining 0.56 QALYs at a cost of $6975 for an ICER of $12 410 per QALY compared with laser treatment plus triamcinolone. Monotherapy with a VEGF inhibitor achieved similar outcomes to combination therapy with laser treatment plus a VEGF inhibitor. Laser monotherapy and triamcinolone monotherapy were less effective and more costly than combination therapy. RESULTS OF SENSITIVITY ANALYSIS: VEGF inhibitor monotherapy was sometimes preferred over laser treatment plus a VEGF inhibitor, depending on the reduction in quality of life with loss of visual acuity. When the VEGF inhibitor bevacizumab was as effective as ranibizumab, it was preferable because of its lower cost. LIMITATION: Long-term outcome data for treated and untreated diseases are limited. CONCLUSION: The most effective treatment of DME is VEGF inhibitor injections with or without laser treatment. This therapy compares favorably with cost-effective interventions for other conditions. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.


Subject(s)
Anti-Inflammatory Agents/economics , Diabetic Retinopathy/therapy , Laser Therapy/economics , Macular Edema/therapy , Triamcinolone/economics , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Administration, Ophthalmic , Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal, Humanized/economics , Antibodies, Monoclonal, Humanized/therapeutic use , Bevacizumab , Combined Modality Therapy , Cost-Benefit Analysis , Diabetic Retinopathy/complications , Disease Progression , Female , Humans , Macular Edema/complications , Male , Markov Chains , Middle Aged , Quality-Adjusted Life Years , Receptors, Vascular Endothelial Growth Factor/economics , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Recombinant Fusion Proteins/economics , Recombinant Fusion Proteins/therapeutic use , Treatment Outcome , Triamcinolone/therapeutic use , Vascular Endothelial Growth Factor A/economics , Visual Acuity
15.
Adv Ther ; 30(12): 1111-27, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24310208

ABSTRACT

INTRODUCTION: This study compared the number of, and expenditures on, first-line intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections between patients who were treated with aflibercept or ranibizumab for wet age-related macular degeneration (AMD). METHODS: This was a retrospective cohort study based on U.S. administrative claims data. Selected patients had initiated first-line intravitreal anti-VEGF treatment with ranibizumab or aflibercept (index date) between November 18, 2011 and April 30, 2013, were aged ≥ 18 years on the index date, had 12 months of continuous insurance enrollment prior to the index date (baseline period), were diagnosed with wet AMD during the baseline period or on the index date, and had at least 6 or 12 months of follow-up enrollment after the index date without switching to a different anti-VEGF agent (follow-up periods). Outcomes measured within the 6 and 12 month follow-up periods included the number of, and healthcare expenditures on, intravitreal anti-VEGF injections. Multivariable regressions compared the outcomes between aflibercept and ranibizumab. RESULTS: The 6 months analyses included 319 aflibercept patients and 1,054 ranibizumab patients (12 month analyses: 57 and 374, respectively). Over the first 6 months after the index date, neither the number of injections (aflibercept mean = 3.8 ± 1.6; ranibizumab mean = 3.9 ± 1.9) nor the expenditures on injections (aflibercept mean = $7,468 ± $4,211; ranibizumab mean = $7,816 ± $4,834) differed significantly between aflibercept patients and ranibizumab patients (in multivariable regression treating ranibizumab as reference: incidence rate ratio = 0.97, 95% confidence interval [CI] 0.91-1.03, P = 0.277; cost ratio = 0.96, 95% CI 0.89-1.04, P = 0.338). Differences were also insignificant in the 12 month analyses. The overall mean days between injections differed by only 1.8 (95% CI 1.3-2.3) days between the aflibercept patients and ranibizumab patients (42.4 and 40.6, respectively). CONCLUSION: Aflibercept and ranibizumab were used at a similar frequency resulting in similar intravitreal anti-VEGF injection healthcare expenditures among wet AMD patients initiating first-line intravitreal anti-VEGF treatment.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Health Care Costs , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Wet Macular Degeneration/drug therapy , Age Factors , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/economics , Cohort Studies , Cost-Benefit Analysis , Databases, Factual , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Intravitreal Injections , Linear Models , Male , Middle Aged , Multivariate Analysis , Poisson Distribution , Ranibizumab , Receptors, Vascular Endothelial Growth Factor/economics , Recombinant Fusion Proteins/economics , Retrospective Studies , Risk Assessment , Severity of Illness Index , Sex Factors , Time Factors , Treatment Outcome , United States , Vascular Endothelial Growth Factor A/administration & dosage , Wet Macular Degeneration/diagnosis
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