Sujet(s)
Acétamides , Effets secondaires indésirables des médicaments , Kératose actinique/traitement médicamenteux , Morpholines , Pyridines , Ulcère cutané , Acétamides/administration et posologie , Acétamides/effets indésirables , Acétamides/économie , Recherche comparative sur l'efficacité , Analyse coût-bénéfice , Coûts des médicaments , Effets secondaires indésirables des médicaments/diagnostic , Effets secondaires indésirables des médicaments/étiologie , Antienzymes/administration et posologie , Antienzymes/effets indésirables , Antienzymes/économie , Humains , Morpholines/administration et posologie , Morpholines/effets indésirables , Morpholines/économie , Pyridines/administration et posologie , Pyridines/effets indésirables , Pyridines/économie , Ulcère cutané/induit chimiquement , Ulcère cutané/diagnostic , Résultat thérapeutiqueSujet(s)
Coûts des médicaments/statistiques et données numériques , Méthotrexate/économie , Acide mycophénolique/économie , Uvéite/traitement médicamenteux , Analyse coût-bénéfice , Antienzymes/économie , Antienzymes/usage thérapeutique , Humains , Immunosuppresseurs/usage thérapeutique , Méthotrexate/usage thérapeutique , Acide mycophénolique/usage thérapeutique , Uvéite/économieRÉSUMÉ
ObjectivesãMedical expenses for diabetes differ between Japan's 47 prefectures. The medical care expenditure regulation plan aims to reduce regional differences in outpatient medical costs through prevention of severe diabetes, promotion of specific health checkups and specific health guidance, promotion of generic drugs, and proper use of medicines. To achieve this goal, we need to conduct an in-depth analysis of inter-prefecture differences in diabetes care expenses. This study analyzed regional differences in prescription fees for dipeptidyl peptidase-4 (DPP-4) inhibitors and the use of generic sulfonylureas (SUs), glinides, biguanides, α-glucosidase inhibitors (α-GIs), and thiazoline derivatives, using the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). Furthermore, we analyzed regional differences in consultancy fees for dialysis prevention.MethodsãWe analyzed the 2nd NDB Open Data Japan website of the Ministry of Health, Labor, and Welfare. Pearson's correlation coefficient (r) was used to evaluate the relationship between the medical costs of diabetes and each factor. The correlation coefficient was analyzed with Student's t-test, and a P-value<0.05 was considered statistically significant.ResultsãRegarding oral hypoglycemic drugs, prefectures with a large number of DPP-4 inhibitors tended to have higher medical costs of diabetes (r=0.40, P=0.0048). Furthermore, such expenses tended to be low in prefectures where the use of generic SU drugs was high (r=-0.43, P=0.0023).ConclusionsãIn conclusion, the results revealed regional differences in the use of DPP-4 inhibitors and generic SU drugs, which may contribute to the regional differences in medical expenses for diabetes. This study suggests that NDB open data are useful for policy making to reduce regional differences in outpatient medical costs of diabetes.
Sujet(s)
Services de santé communautaires/économie , Coûts indirects de la maladie , Diabète/traitement médicamenteux , Diabète/économie , Antienzymes/administration et posologie , Antienzymes/économie , Coûts des soins de santé , Hypoglycémiants/administration et posologie , Hypoglycémiants/économie , Sulfonylurées/administration et posologie , Sulfonylurées/économie , Analyse de données , Diabète/prévention et contrôle , Dipeptidyl peptidase 4 , Humains , Japon , Frais d'ordonnance , Orientation vers un spécialiste/économieRÉSUMÉ
BACKGROUND: Improved survival after a cardiovascular event has led to an expanding patient population at very high risk of recurrent events. Reduction in low-density lipoprotein cholesterol, and thus implicitly non-high-density lipoprotein cholesterol, to guideline-recommended goals is a key tenet of secondary prevention. Yet, standard-of-care treatment with statin (with or without ezetimibe) often leaves a high risk of preventable cardiovascular events. Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9), highly efficacious lipid-lowering treatments that confer reduction in cardiovascular events and death, clearly have a role in the personalized management of these very-high-risk patients. Given budget constraints, however, their integration into the health care pathway merits health economic considerations. Consequently, it is important to identify challenges at the crossroads of the clinical and economic dimensions. FINDINGS AND CONCLUSION: Health economic analyses involve application of modeling scenarios integrating multiple parameters to ultimately yield values for quality-adjusted life-years and cost-effectiveness ratios. To date, these analyses have led to widely variable estimates of these benchmarks for PCSK9 inhibitors, causing confusion among stakeholders in the health care pathway. Clearly, a consensual approach to the conduct and reporting of health economic analyses involving all players, including noneconomists such as clinicians and patient advocates, is essential to bridge the gap between the clinical needs of patients and financial access to PCSK9 inhibition.
Sujet(s)
Athérosclérose/traitement médicamenteux , Athérosclérose/économie , Antienzymes/économie , Antienzymes/usage thérapeutique , Inhibiteurs de PCSK9 , Cholestérol LDL , Humains , Modèles économiques , Proprotéine convertase 9/métabolisme , Facteurs de risqueRÉSUMÉ
BACKGROUND: Gaucher disease type 1 (GD1) is a rare, genetic, lysosomal storage disease with no cure. Current treatment options include intravenous (IV) enzyme replacement therapy ([ERT]; imiglucerase, velaglucerase alfa, or taliglucerase alfa) or oral substrate reduction therapy ([SRT]; eliglustat or miglustat). The cost to U.S. payers of an IV-administered drug can vary depending on the site of care (i.e., home, outpatient clinic, or hospital setting). Treatment with oral eliglustat may present an opportunity for cost savings. OBJECTIVE: To evaluate the budget impact from a U.S. payer perspective associated with transitioning patients receiving ERTs to the oral SRT eliglustat for the treatment of adults with GD1. METHODS: A budget impact model estimated the change in pharmaceutical and administration costs resulting from increasing the market share of eliglustat from 12% (current) to 44% (new). The market share for eliglustat was drawn equally from existing shares of imiglucerase (40%) and velaglucerase alfa (40%) and assumed to be static over the analysis period. ERT costs were adjusted to account for site of care-based markup and the proportion of patients receiving infusions in each site of care (home, infusion center, or hospital outpatient). Annual ERT costs were calculated assuming a biweekly dose of 47.4 U per kg, a 72-kg patient weight, and 24 infusions per year. The effect of key variables was tested in the sensitivity analyses. All costs are expressed in 2017 U.S. dollars. RESULTS: In a new plan with 5 million members and 25 GD1 treated patients, increased use of eliglustat resulted in an annual savings of $1,526,710 and a total savings of $4,580,130 (13.6%) over 3 years. The corresponding annual per member per month savings was $0.025. This is further illustrated in the sensitivity and scenario analyses where the use of eliglustat was cost saving in all cases. Shifting more patients receiving ERT in the hospital outpatient setting to eliglustat resulted in increased savings. CONCLUSIONS: Based on these analyses, increased use of eliglustat resulted in meaningful cost savings to a payer's overall budget. Cost savings are highest among patients switching from ERT administered in a hospital outpatient setting. The results suggest that cost savings are also likely achievable from initiating patients on oral eliglustat instead of infusion-based therapy from the outset of treatment. DISCLOSURES: This study was sponsored by Sanofi Genzyme. Evidera received funding from Sanofi Genzyme to conduct this study and prepare the manuscript. The sponsor collaborated on the study design, analysis, interpretation of results, and writing of the manuscript. Nalysnyk is an employee of and shareholder in Sanofi Genzyme. Ward, Cele, and Uyei are employees of Evidera, which provides consulting and other research services to biopharmaceutical companies. Sugarman was also an Evidera employee when the study was being conducted and the manuscript written. This study was presented as a poster at the Academy of Managed Care Pharmacy Nexus 2016, October 3-6, 2016; National City, MD, and at the International Society for Pharmacoeconomics and Outcomes Research, 22nd Annual International Meeting; May 20-24, 2017; Boston, MA.
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Budgets , Coûts des médicaments , Antienzymes/administration et posologie , Antienzymes/économie , Maladie de Gaucher/traitement médicamenteux , Maladie de Gaucher/économie , Pyrrolidines/administration et posologie , Pyrrolidines/économie , Administration par voie orale , Prise de décision clinique , Économies , Analyse coût-bénéfice , Techniques d'aide à la décision , Calendrier d'administration des médicaments , Substitution de médicament/économie , Thérapie enzymatique substitutive/économie , Maladie de Gaucher/diagnostic , Maladie de Gaucher/épidémiologie , Glucosylceramidase/administration et posologie , Glucosylceramidase/économie , Humains , Perfusions veineuses , Modèles économiques , Facteurs temps , Résultat thérapeutique , États-Unis/épidémiologieRÉSUMÉ
The objective of this study was to review available health economic evaluations of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors. These drugs reduce low-density lipid cholesterol levels and cardiovascular risk, but their cost effectiveness has been questioned. We searched Medline and Embase for economic evaluations in any language at any time. Studies were included if they analysed any PCSK9 inhibitor compared with either statin alone or in combination with ezetimibe or any other therapy considered standard prior to the introduction of PCSK9 inhibitors. We found ten full health economic evaluations of PCSK9 inhibitors, two from Europe and eight from the United States (US). Six of the eight from the US were from two different consortia that analysed PCSK9 inhibitors at different stages through the development of evidence. All studies generally reported incremental cost-effectiveness ratios above suggested thresholds for cost effectiveness, except one study from Spain. The results of this review indicate that PCSK9 inhibitors in general are not cost effective at the current prices, but lower prices may change the results.
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Anticholestérolémiants/économie , Analyse coût-bénéfice/statistiques et données numériques , Antienzymes/économie , Hypercholestérolémie/économie , Anticholestérolémiants/usage thérapeutique , Association de médicaments/économie , Antienzymes/usage thérapeutique , Ézétimibe/économie , Ézétimibe/usage thérapeutique , Humains , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase/économie , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase/usage thérapeutique , Hypercholestérolémie/traitement médicamenteux , Inhibiteurs de PCSK9 , Années de vie ajustées sur la qualitéRÉSUMÉ
The effectiveness and economics of polyvinyl sulfonic acid (PVSA) as a ribonuclease inhibitor for in vitro systems is reported. PVSA was shown to inhibit RNA cleavage in the presence of RNase A as well as in the presence of Escherichia coli lysate, suggesting that PVSA can act as a broader ribonuclease inhibitor. In addition, PVSA was shown to improve the integrity of mRNA transcripts by up to 5-fold in vitro as measured by their translational viability. Improved preservation of mRNA transcripts in the presence of PVSA under common RNA storage conditions is also reported. A cost comparison with commercially available RNAse inhibitors indicates the economic practicality of PVSA which is approximately 1,700 times less expensive than commonly used ribonuclease inhibitors. PVSA can also be separated from RNA by alcohol precipitation for applications that may be sensitive to the presence of PVSA.
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Protéines bactériennes/antagonistes et inhibiteurs , Antienzymes/pharmacologie , Polyvinyles/pharmacologie , Biosynthèse des protéines , ARN messager/métabolisme , Ribonucléases/antagonistes et inhibiteurs , Acides sulfoniques/pharmacologie , Protéines bactériennes/génétique , Protéines bactériennes/métabolisme , Dosages enzymatiques , Antienzymes/composition chimique , Antienzymes/économie , Escherichia coli/enzymologie , Escherichia coli/génétique , Cinétique , Polyvinyles/composition chimique , Polyvinyles/économie , Stabilité de l'ARN , ARN messager/composition chimique , ARN messager/génétique , Ribonucléases/génétique , Ribonucléases/métabolisme , Fractions subcellulaires/métabolisme , Acides sulfoniques/composition chimique , Acides sulfoniques/économie , Transcription génétiqueRÉSUMÉ
PURPOSE OF REVIEW: Cholesterol management in the current era is discussed. Aggressive reduction of low density lipoprotein (LDL) cholesterol plays a key role in primary and secondary prevention of heart disease. Statins are the recommended first-line therapy in patients with hyperlipidemia; however, additional complementary approaches are frequently needed for patients who fail to reach their target LDL. RECENT FINDINGS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are novel drugs that provide dramatic lowering of LDL and promise outcome benefit. Despite great enthusiasm about their cardiovascular benefit, concerns have been raised regarding their cost and added value to the healthcare system. Although cost-effectiveness studies have yielded inconclusive results, analyses suggest that the current cost of PCSK9 inhibitors is disproportionately high and must be significantly reduced to add positive net benefit to healthcare system. PCSK9 inhibitors significantly lower LDL cholesterol. Further outcome data and cost-effectiveness analyses are needed to overcome the current barriers with PCSK9 inhibitors that patients, physicians, and payers face.
Sujet(s)
Cholestérol LDL/sang , Antienzymes/usage thérapeutique , Cardiopathies/prévention et contrôle , Inhibiteurs de PCSK9 , Antienzymes/économie , Humains , Inhibiteurs de l'hydroxyméthylglutaryl-CoA réductase/usage thérapeutique , Hypercholestérolémie/traitement médicamenteux , Prévention primaire , Prévention secondaireRÉSUMÉ
BACKGROUND: International guidelines recommend nintedanib (OFEV®) as an option for the treatment of idiopathic pulmonary fibrosis (IPF). OBJECTIVE: The objective of this study was to assess the cost effectiveness of nintedanib versus pirfenidone, N-acetylcysteine and best supportive care (BSC) for the treatment of IPF from a UK payer's perspective. METHODS: A Markov model was designed to capture the changes in the condition of adults with IPF. Efficacy outcomes included mortality, lung function decline and acute exacerbations. Treatment safety (serious adverse events) and tolerability (overall discontinuation) were also considered. The baseline risk of these events was derived from patient-level data from the placebo arms of nintedanib clinical trials (TOMORROW, INPULSIS-1, INPULSIS-2). A network meta-analysis (NMA) was conducted to estimate the relative effectiveness of the comparator treatments. Quality of life and healthcare resource use data from the clinical trials were also incorporated in the economic model. RESULTS: Nintedanib showed statistically significant differences against placebo on acute exacerbation events avoided and lung function decline. In the cost-effectiveness analysis, the results were split between two treatments with relative low costs and modest effectiveness (BSC and N-acetylcysteine) and two that showed improved effectiveness (lung function) and higher costs (nintedanib and pirfenidone). All comparators were assumed to have similar projected survival and the difference in quality-adjusted life-years (QALYs) was driven by the acute exacerbations and lung function estimates. In the base-case deterministic pairwise comparison with pirfenidone, nintedanib was found to have fewer acute exacerbations and resulted in less costs and more QALYs gained. CONCLUSIONS: Compared with BSC (placebo), nintedanib and pirfenidone were the only treatments to show statistical significance in the efficacy parameters. We found substantial uncertainty in the overall cost-effectiveness results between nintedanib and pirfenidone. N-Acetylcysteine was largely similar to BSC but with a worse survival profile. INPULSIS-1 and INPULSIS-2 ClinicalTrials.gov numbers, NCT01335464 and NCT01335477.
Sujet(s)
Acétylcystéine/usage thérapeutique , Fibrose pulmonaire idiopathique/traitement médicamenteux , Indoles/usage thérapeutique , Pyridones/usage thérapeutique , Acétylcystéine/effets indésirables , Acétylcystéine/économie , Adulte , Analyse coût-bénéfice , Antienzymes/effets indésirables , Antienzymes/économie , Antienzymes/usage thérapeutique , Humains , Fibrose pulmonaire idiopathique/économie , Fibrose pulmonaire idiopathique/mortalité , Indoles/effets indésirables , Indoles/économie , Chaines de Markov , Modèles économiques , Pyridones/effets indésirables , Pyridones/économie , Qualité de vie , Années de vie ajustées sur la qualité , Essais contrôlés randomisés comme sujet , Résultat thérapeutique , Royaume-UniSujet(s)
Amidohydrolases/antagonistes et inhibiteurs , Encéphalopathies/induit chimiquement , N-oxydes cycliques/effets indésirables , Développement de médicament/méthodes , Industrie pharmaceutique , Antienzymes/effets indésirables , Pyridines/effets indésirables , Amidohydrolases/métabolisme , Animaux , Encéphalopathies/diagnostic , Commerce , N-oxydes cycliques/économie , Coûts des médicaments , Développement de médicament/économie , Développement de médicament/éthique , Industrie pharmaceutique/économie , Industrie pharmaceutique/éthique , Antienzymes/économie , Humains , Sécurité des patients , Pyridines/économie , Appréciation des risques , Spécificité d'espèceRÉSUMÉ
OBJECTIVE: To characterize the conclusions and production of nonsystematic reviews about neuraminidase inhibitors relative to financial competing interests held by the authors. STUDY DESIGN AND SETTING: We searched for articles about neuraminidase inhibitors and influenza (January 2005 to April 2015), identifying nonsystematic reviews and grading them according to the favorable/nonfavorable presentation of evidence on safety and efficacy. We recorded financial competing interests disclosed in the reviews and from other articles written by their authors. We measured associations between competing interests, author productivity, and conclusions. RESULTS: Among 213 nonsystematic reviews, 138 (65%) presented favorable conclusions. Financial competing interests were identified for 26% (137/532) of authors; 51% (108/213) of reviews were associated with a financial competing interest. Reviews produced exclusively by authors with financial competing interests (33%; 71/213) were more likely to present favorable conclusions than reviews with no competing interests (risk ratio 1.27; 95% confidence interval 1.03-1.55). Authors with financial competing interests published more articles about neuraminidase inhibitors than their counterparts. CONCLUSION: Half of nonsystematic reviews about neuraminidase inhibitors included an author with a financial competing interest. Reviews produced exclusively by these authors were more likely to present favorable conclusions, and authors with financial competing interests published a greater number of reviews.
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Auteur , Conflit d'intérêts/économie , Antienzymes/économie , Sialidase/antagonistes et inhibiteurs , Soutien financier à la recherche comme sujet/économie , Littérature de revue comme sujet , Industrie pharmaceutique/économie , Humains , Sialidase/économieSujet(s)
Dérivés de l'aniline/économie , Agrément de médicaments/économie , Antienzymes/économie , Nitriles/économie , Quinoléines/économie , Médecine d'État , Dérivés de l'aniline/usage thérapeutique , Antienzymes/usage thérapeutique , Humains , Leucémie myéloïde/traitement médicamenteux , Nitriles/usage thérapeutique , Quinoléines/usage thérapeutique , Royaume-UniRÉSUMÉ
OBJECTIVES: Specialty drugs often offer medical advances but are frequently subject to high cost sharing. This is particularly true with Medicare Part D, where after meeting a deductible, patients without low-income subsidies (non-LIS) typically face 25% to 33% coinsurance (initial coverage phase with "specialty tier" cost sharing), followed by ~50% coinsurance (coverage gap phase), and then 5% coinsurance (catastrophic phase). Yet, no studies have examined the impact of such high cost sharing on specialty drug initiation under Part D. Oral tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML), making it an apt case study. STUDY DESIGN: A retrospective claims-based analysis utilizing 2011 to 2013 100% Medicare claims. METHODS: TKI initiation rates and time to initiation were compared between fee-for-service non-LIS Part D patients newly diagnosed with CML and their LIS counterparts who faced nominal cost sharing of ≤ $5. RESULTS: The first 30-day TKI fill "straddled" benefit phases, for a mean out-of-pocket cost of $2600 or more for non-LIS patients. Non-LIS patients were less likely than LIS patients to have a TKI claim within 6 months of diagnosis (45.3% vs 66.9%; P < .001) and those initiating a TKI took twice as long to fill it (mean = 50.9 vs 23.7 days; P < .001). Cox regressions controlling for sociodemographic, clinical, and plan characteristics confirmed descriptive findings (hazard ratio, 0.59; 95% CI, 0.45-0.76). Extensive sensitivity analyses confirmed the robustness of our findings. CONCLUSIONS: High cost sharing was associated with reduced and/or delayed initiation of TKIs. We discuss policy strategies to reduce current financial barriers that adversely impact access to critical therapies under Medicare Part D.
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Antinéoplasiques/économie , Participation aux coûts/économie , Antienzymes/économie , Leucémie myéloïde/traitement médicamenteux , Leucémie myéloïde/économie , Medicare part D (USA)/économie , Pyrazoles/économie , Pyrimidines/économie , Sujet âgé , Sujet âgé de 80 ans ou plus , Antinéoplasiques/usage thérapeutique , Maladie chronique/traitement médicamenteux , Maladie chronique/économie , Participation aux coûts/statistiques et données numériques , Antienzymes/usage thérapeutique , Femelle , Dépenses de santé/statistiques et données numériques , Humains , Mâle , Medicare part D (USA)/statistiques et données numériques , Pyrazoles/usage thérapeutique , Pyrimidines/usage thérapeutique , Études rétrospectives , États-UnisRÉSUMÉ
BACKGROUND: Mycophenolate mofetil (MMF) is effective in decreasing rejection and graft loss in renal transplant patients. Enteric-coated mycophenolate sodium (EC-MPS) was designed to reduce MMF gastrointestinal (GI) effects. Dose manipulations in MMF/EC-MPS produce GI tolerability, increasing the risk of rejection. Significant differences in tolerance of MMF/EC-MPS may have economic influence in transplant efficacy outcomes. Herein, we performed a pharmacoeconomic evaluation of acute rejection incidence and interventions in GI-intolerant patients using MMF/EC-MPS. METHODS: A cost-effectiveness analysis was performed through a decision tree model with a 1-year time horizon estimating costs and effectiveness of MMF and EC-MPS in renal transplant patients with GI intolerance. The costs and use of resources (US dollars; USD) were from payer perspective (Mexican Social Security). Primary health outcomes were mean cost of acute rejection and GI adverse events treatment. A probabilistic sensitivity analysis (PSA) was generated to test robustness of the model. RESULTS: Calculated incidence of MMF GI intolerance was 44%, and calculated rejection incidence for MMF was 24.05%. Calculated incidence of EC-MPS GI intolerance was 29%, and calculated rejection incidence for EC-MPS was 20.1% Total cost of MMF with GI intolerance during 1-year period plus cost of treating one rejection sums $752,107.25 USD. Total cost of EC-MPS with GI intolerance plus cost of treating one rejection sums $638,018.97 USD. CONCLUSION: EC-MPS-based treatment is a cost-saving alternative vs MMF in GI-intolerant kidney transplant patients. PSA supports the decision to utilize EC-MPS based on cost-effectiveness analysis.
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Tolérance aux médicaments , Pharmacoéconomie , Maladies gastro-intestinales/induit chimiquement , Rejet du greffon/traitement médicamenteux , Transplantation rénale/effets indésirables , Acide mycophénolique/administration et posologie , Analyse coût-bénéfice , Relation dose-effet des médicaments , Antienzymes/administration et posologie , Antienzymes/économie , Antienzymes/pharmacocinétique , Études de suivi , Maladies gastro-intestinales/économie , Maladies gastro-intestinales/métabolisme , Rejet du greffon/économie , Rejet du greffon/métabolisme , Humains , Immunosuppresseurs/usage thérapeutique , Incidence , Transplantation rénale/économie , Acide mycophénolique/économie , Acide mycophénolique/pharmacocinétique , Comprimés entérosolubles , Facteurs tempsSujet(s)
Anticorps monoclonaux/économie , Anticorps monoclonaux/usage thérapeutique , Analyse coût-bénéfice , Antienzymes/économie , Antienzymes/usage thérapeutique , Inhibiteurs de PCSK9 , Anticorps monoclonaux humanisés , Anticholestérolémiants/économie , Anticholestérolémiants/usage thérapeutique , Coûts des médicaments , HumainsRÉSUMÉ
The purpose of this article is to review eliglustat tartrate, a substrate reduction therapy, for the treatment of Gaucher disease type 1 (GD1). GD is an rare inborn error of metabolism caused by accumulation of lipid substrates such as glucosylceramide within the monocyte-macrophage system that affects the body by causing enlargement of the spleen and liver, destruction of bone, and abnormalities of the lungs and blood, such as anemia, thrombocytopenia, and leukopenia. GD is classified into three types: GD1, a chronic and non-neuronopathic disease accounting for 95% of GD cases; and types 2 and 3 (GD2 GD3) which are more progressive diseases with no approved drugs available at this time. Treatment options for GD1 include enzyme replacement therapy and substrate reduction therapy. Eliglustat works by inhibiting UDP-glucosylceramide synthase, the first enzyme that catalyzes the biosynthesis of glycosphingolipids, thus reducing the load of glucosylceramide influx into the lysosome. Eliglustat was approved by the US Food and Drug Administration after three Phase I, two Phase II, and two Phase III clinical trials. The dose of eliglustat is 84 mg twice a day or once daily depending on the cytochrome P450 2D6 genotype of the patient.
Sujet(s)
Antienzymes/usage thérapeutique , Maladie de Gaucher/traitement médicamenteux , Glucosyltransferases/antagonistes et inhibiteurs , Pyrrolidines/usage thérapeutique , Adulte , Animaux , Analyse coût-bénéfice , Cytochrome P-450 CYP2D6/génétique , Cytochrome P-450 CYP2D6/métabolisme , Calendrier d'administration des médicaments , Coûts des médicaments , Antienzymes/administration et posologie , Antienzymes/effets indésirables , Antienzymes/économie , Antienzymes/pharmacocinétique , Maladie de Gaucher/diagnostic , Maladie de Gaucher/économie , Maladie de Gaucher/enzymologie , Maladie de Gaucher/génétique , Génotype , Glucosylcéramides/biosynthèse , Glucosyltransferases/métabolisme , Humains , Pharmacogénétique , Phénotype , Pyrrolidines/administration et posologie , Pyrrolidines/effets indésirables , Pyrrolidines/économie , Pyrrolidines/pharmacocinétique , Résultat thérapeutiqueRÉSUMÉ
In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41-2272 might occur primarily by the modulation of the host immune response through macrophage activation. .
Sujet(s)
Animaux , Souris , Adipocytes blancs/métabolisme , Ananas/composition chimique , Compléments alimentaires , Fruit/composition chimique , Hypoglycémiants/isolement et purification , Déchets industriels/analyse , Extraits de plantes/isolement et purification , Adipogenèse , Adipocytes blancs/cytologie , Antioxydants/composition chimique , Antioxydants/économie , Antioxydants/isolement et purification , Antienzymes/composition chimique , Antienzymes/économie , Antienzymes/isolement et purification , Industrie de la transformation des aliments/économie , Glycosylation , Glycerolphosphate dehydrogenase/antagonistes et inhibiteurs , Glycerolphosphate dehydrogenase/métabolisme , Inhibiteurs des glycoside hydrolases/composition chimique , Inhibiteurs des glycoside hydrolases/économie , Inhibiteurs des glycoside hydrolases/isolement et purification , Hypoglycémiants/composition chimique , Hypoglycémiants/économie , Inde , Déchets industriels/économie , Lipotropes/composition chimique , Lipotropes/économie , Lipotropes/isolement et purification , Extraits de plantes/composition chimique , Extraits de plantes/économie , Solvants/composition chimique , alpha-Amylases/antagonistes et inhibiteurs , alpha-Amylases/métabolismeRÉSUMÉ
Ranolazine has been shown to decrease angina pectoris frequency and nitroglycerin consumption. We assessed the cost-effectiveness of ranolazine when added to standard-of-care (SoC) antianginals compared with SoC alone in patients with stable coronary disease experiencing ≥3 attacks/week. A Markov model utilizing a societal perspective, a 1-month cycle length, and a 1-year time horizon was developed to estimate costs (2013 US$) and quality-adjusted life years (QALYs) for patients receiving and not receiving ranolazine. Patients entered the model in 1 of the 4 angina frequency health states based upon Seattle Angina Questionnaire angina frequency (SAQAF) scores (100=no; 61 to 99=monthly; 31 to 60=weekly; and 0 to 30=daily angina) and were allowed to transition between states or to death based upon probabilities derived from the Efficacy of Ranolazine in Chronic Angina and other studies. Patients not responding to ranolazine in month 1 (not improving ≥1 SAQAF health state) were assumed to discontinue ranolazine and behave like SoC patients. Ranolazine patients lived a mean of 0.700 QALYs at a cost of $15,661. Those not receiving ranolazine lived 0.659 QALYs and at a cost of $14,321. The incremental cost-effectiveness ratio (ICER) for the addition of ranolazine was $32,682/QALY. The ICER was most sensitive to ranolazine cost but only exceeded $50,000/QALY when the cost of ranolazine increased >32% above base case. The ICER remained <$50,000/QALY when indirect costs were excluded, and mortality rates were assumed equivalent between SAQAF health states. Monte Carlo simulation found ranolazine cost-effective in 97% of 10,000 iterations at a $50,000/QALY willingness-to-pay threshold. In conclusion, ranolazine added to SoC is cost-effective in patients with weekly or daily angina.
Sujet(s)
Acétanilides/usage thérapeutique , Angor stable/traitement médicamenteux , Coûts des médicaments , Pipérazines/usage thérapeutique , Norme de soins/économie , Acétanilides/administration et posologie , Acétanilides/économie , Angor stable/économie , Maladie chronique , Analyse coût-bénéfice , Relation dose-effet des médicaments , Méthode en double aveugle , Antienzymes/administration et posologie , Antienzymes/économie , Antienzymes/usage thérapeutique , Femelle , Études de suivi , Humains , Mâle , Pipérazines/administration et posologie , Pipérazines/économie , Années de vie ajustées sur la qualité , Ranolazine , États-UnisRÉSUMÉ
BACKGROUND: Ranolazine is an antianginal agent that was approved in the EU in 2008 as an add-on therapy for symptomatic chronic angina pectoris treatment in patients who are inadequately controlled by, or are intolerant to, first-line antianginal therapies. These patients' quality of life is significantly affected by more frequent angina events, which increase the risk of revascularization. OBJECTIVE: To assess the cost-utility of ranolazine versus placebo as an add-on therapy for the symptomatic treatment of patients with chronic angina pectoris in Spain. METHODS: A decision tree model with 1-year time horizon was designed. Transition probabilities and utility values for different angina frequencies were obtained from the literature. Costs were obtained from Spanish official DRGs for patients with chronic angina pectoris. We calculated the incremental cost-utility ratio of using ranolazine compared with a placebo. Sensitivity analyses, by means of Monte Carlo simulations, were performed. Acceptability curves and expected value of perfect information were calculated. RESULTS: The incremental cost-utility ratio was 8,455 per quality-adjusted life-year (QALY) per patient in Spain. Sensitivity analyses showed that if the decision makers' willingness to pay is 15,000 per QALY, the treatment with ranolazine will be cost effective at a 95 % level of confidence. The incremental cost-utility ratio is particularly sensitive to changes in utility values of those non-hospitalized patients with mild or moderate angina frequency. CONCLUSIONS: Ranolazine is a highly efficient add-on therapy for the symptomatic treatment of chronic angina pectoris in patients who are inadequately controlled by, or intolerant to, first-line antianginal therapies in Spain.
Sujet(s)
Acétanilides/économie , Angine de poitrine/traitement médicamenteux , Antienzymes/économie , Pipérazines/économie , Acétanilides/usage thérapeutique , Maladie chronique/traitement médicamenteux , Analyse coût-bénéfice , Antienzymes/usage thérapeutique , Femelle , Humains , Mâle , Chaines de Markov , Adulte d'âge moyen , Pipérazines/usage thérapeutique , Placebo/économie , Ranolazine , EspagneRÉSUMÉ
BACKGROUND: Rapid urbanisation and nutritional transition is fuelling the increased global incidence of type 2 diabetes. Pineapple fruit residue was explored for its nutraceutical properties as an alternative or adjunct to currently available treatment regime. Ethyl acetate and methanolic extracts of pineapple fruit residue were evaluated for anti-diabetic activity in cell free and cell based systems. Specifically, we assessed: (1) antioxidant potential, (2) anti-glycation potential, (3) carbohydrate digestive enzyme inhibition, and (4) lipid accumulation and glycerol-3-phosphate dehydrogenase activity in differentiating 3T3-L1 cells. RESULTS: The active components in the ethyl acetate and methanolic extracts were identified as sinapic acid, daucosterol, 2-methylpropanoate, 2,5-dimethyl-4-hydroxy-3(2H)-furanone, methyl 2-methylbutanoate and triterpenoid ergosterol using DART/HRMS and ESI/HRMS. Micronutrient analysis revealed the presence of magnesium, potassium and calcium. Adipogenic potential, anti-glycation property of the ethyl acetate extract, and DNA damage protection capacity of the methanolic extract are promising. CONCLUSION: Results from this study clearly indicate that pineapple fruit residue could be utilised as a nutraceutical against diabetes and related complications.