Cost-effectiveness of posaconazole in private and public Brazilian hospitals / Rentabilidad del uso de posaconazol en hospitales públicos y privados de Brasil

Background: Posaconazole is used for the prophylaxis of invasive fungal disease (IFD). Previous studies have shown it to be cost-effective compared to fluconazole/itraconazole. However, posaconazole has never been economically evaluated in developing countries. Aims: The aim of the present study was to perform a cost-effectiveness analysis of posaconazole compared to fluconazole in public (SUS) and private hospitals (PHS) in Brazil. Methods: A cost-effectiveness simulation was conducted on the basis of a pivotal study on the use of posaconazole in acute myeloid leukemia (AML) patients, adjusting the costs to Brazilian data. Results: A pharmacoeconomic analysis was performed on a hypothetical sample of 100 patients in each drug group. The total cost of posaconazole use alone was USD$ 220,656.31, whereas that for fluconazole was USD$ 83,875.00. Our results showed that patients with IFD remain hospitalized for an additional 12 days, at an average cost of USD$ 850.85 per patient per day. The total money spent by PHS for 100 patients for 100 days was USD$ 342,318.00 for the posaconazole group and USD$ 302,039.00 for the fluconazole group. An analysis of sensitivity (10%) revealed no intergroup difference. Conclusions: In Brazil posaconazole is cost-effective, and should be considered for the prophylaxis of patients with AMD/myelodysplasia (AML/MDS) undergoing chemotherapy

Antecedentes: El posaconazol se utiliza para la profilaxis de la enfermedad fúngica invasora (EFI). Algunos estudios han demostrado su rentabilidad en comparación con el fluconazol o el itraconazol. Sin embargo, el posaconazol nunca se había evaluado económicamente en el contexto de los países en vías de desarrollo. Objetivos: El objetivo de este estudio fue realizar un análisis de rentabilidad del posaconazol en comparación con el fluconazol en hospitales públicos (SUS) y hospitales privados (PHS) de Brasil. Métodos: Se realizó una simulación de rentabilidad basada en un estudio fundamental para el uso de posaconazol en pacientes con leucemia mieloide aguda (LMA) que adaptaba los costes a los datos brasileños. Resultados: Se realizó un análisis farmacoeconómico de 100 pacientes con cada grupo tratado. El gasto total de 100 días para los antifúngicos evaluados fue 220.656,31 $ para el posaconazol y de 83.875,00 $ para el fluconazol. Los pacientes con EFI permanecen en el hospital una media de 12 días más a un coste medio de 850,85 $ por día y paciente. El gasto total en PHS de 100 pacientes fue 342.318,00 $ para el grupo del posaconazol y 302.039,00 $ para el del fluconazol. No hubo diferencias entre los grupos al realizar un análisis de sensibilidad al 10%. Conclusiones: En Brasil, el posaconazol es rentable y debe tenerse en cuenta al elegir la profilaxis ideal para pacientes con LMA tratados con quimioterapia

Cost-effectiveness of posaconazole in private and public Brazilian hospitals.

BACKGROUND: Posaconazole is used for the prophylaxis of invasive fungal disease (IFD). Previous studies have shown it to be cost-effective compared to fluconazole/itraconazole. However, posaconazole has never been economically evaluated in developing countries. AIMS: The aim of the present study was to perform a cost-effectiveness analysis of posaconazole compared to fluconazole in public (SUS) and private hospitals (PHS) in Brazil. METHODS: A cost-effectiveness simulation was conducted on the basis of a pivotal study on the use of posaconazole in acute myeloid leukemia (AML) patients, adjusting the costs to Brazilian data. RESULTS: A pharmacoeconomic analysis was performed on a hypothetical sample of 100 patients in each drug group. The total cost of posaconazole use alone was USD$ 220,656.31, whereas that for fluconazole was USD$ 83,875.00. Our results showed that patients with IFD remain hospitalized for an additional 12 days, at an average cost of USD$ 850.85 per patient per day. The total money spent by PHS for 100 patients for 100 days was USD$ 342,318.00 for the posaconazole group and USD$ 302,039.00 for the fluconazole group. An analysis of sensitivity (10%) revealed no intergroup difference. CONCLUSIONS: In Brazil posaconazole is cost-effective, and should be considered for the prophylaxis of patients with AMD/myelodysplasia (AML/MDS) undergoing chemotherapy.

Cost-Effectiveness of Posaconazole Tablets for Invasive Fungal Infections Prevention in Acute Myelogenous Leukemia or Myelodysplastic Syndrome Patients in Spain.

INTRODUCTION: Posaconazole is superior to fluconazole (FLU) and itraconazole (ITRA) in the prevention of invasive fungal diseases (IFDs) in neutropenic patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). A new tablet formulation of posaconazole with improved pharmacokinetic and pharmacodynamic properties compared to posaconazole oral solution has recently been approved. The objective of this study is to estimate the cost-effectiveness of the newly developed posaconazole tablets versus FLU oral suspension or ITRA oral solution for preventing IFDs in high-risk neutropenic patients with AML or MDS and from the perspective of the Spanish National Health System (NHS). METHODS: A previously validated economic model was used. The probabilities of experiencing an IFD, an IFD-related death or death from other causes over 100 days were based on clinical trial data and input into a decision tree. Surviving patients were entered into a Markov model to calculate total costs, number of IFDs and number of life-years gained per patient over a lifetime horizon in each disease and treatment group. Two health states, alive and dead, were considered. Health effects were discounted using a rate of 3%. Univariate and probabilistic sensitivity analyses were conducted. RESULTS: During the first 100 days, posaconazole tablets were associated with a lower risk of IFDs (0.046 vs. 0.111), longer life expectancy (2.92 vs. 2.69 years) and lower total costs (€5906.06 vs. €7847.20 per patient) over the patients' lifetimes compared to FLU or ITRA treatments. Thus, posaconazole tablets were more effective and less costly than FLU or ITRA. Probabilistic sensitivity analysis indicated that there was a 79.9% probability of posaconazole tablets being cost-saving compared to FLU or ITRA. CONCLUSION: From the Spanish NHS perspective, posaconazole tablets are cost-effective compared to FLU or ITRA in AML or MSD patients with chemotherapy-induced neutropenia and at high risk for IFDs. FUNDING: MSD Sharp & Dohme.

Economic evaluation of azoles as primary prophylaxis for the prevention of invasive fungal infections in Spanish patients undergoing allogeneic haematopoietic stem cell transplant.

Patients undergoing allogeneic haematopoietic stem cell transplantation (alloHSCT) are at risk of developing invasive fungal infections (IFIs). Even with introduction of oral triazole antifungal agents (fluconazole, itraconazole, posaconazole and voriconazole) IFI-associated morbidity and mortality rates and economic burden remain high. Despite their proven efficacy, it is currently unknown which is the most cost-effective antifungal prophylaxis (AFP) agent. To determine the costs and outcomes associated with AFP, a decision-analytic model was used to simulate treatment in a hypothetical cohort of 1000 patients undergoing alloHSCT from the perspective of the Spanish National Health System. Generic itraconazole was the least costly AFP (€162) relative to fluconazole (€500), posaconazole oral suspension (€8628) or voriconazole (€6850). Compared with posaconazole, voriconazole was associated with the lowest number of breakthrough IFIs (36 vs 60); thus, the model predicted fewer deaths from breakthrough IFI for voriconazole (24) than posaconazole (33), and the lowest predicted costs associated with other licensed antifungal treatment and IFI treatment in a cohort of 1000. Voriconazole resulted in cost savings of €4707 per patient compared with posaconazole. Itraconazole demonstrated a high probability of being cost-effective. As primary AFP in alloHSCT patients 180 days posttransplant, voriconazole was more likely to be cost-effective than posaconazole regarding cost per additional IFI and additional death avoided.

Network Meta-analysis and Pharmacoeconomic Evaluation of Fluconazole, Itraconazole, Posaconazole, and Voriconazole in Invasive Fungal Infection Prophylaxis.

Invasive fungal infections (IFIs) are associated with high mortality rates and large economic burdens. Triazole prophylaxis is used for at-risk patients with hematological malignancies or stem cell transplants. We evaluated both the efficacy and the cost-effectiveness of triazole prophylaxis. A network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating fluconazole, itraconazole capsule and solution, posaconazole, and voriconazole was conducted. The outcomes of interest included the incidences of IFIs and deaths. This was coupled with a cost-effectiveness analysis from patient perspective over a lifetime horizon. Probabilities of transitions between health states were derived from the NMA. Resource use and costs were obtained from the Singapore health care institution. Data on 5,505 participants in 21 RCTs were included. Other than itraconazole capsule, all triazole antifungals were effective in reducing IFIs. Posaconazole was better than fluconazole (odds ratio [OR], 0.35 [95% confidence interval [CI], 0.16 to 0.73]) and itraconazole capsule (OR, 0.25 [95% CI, 0.06 to 0.97]), but not voriconazole (OR, 1.31 [95% CI, 0.43 to 4.01]), in preventing IFIs. Posaconazole significantly reduced all-cause deaths, compared to placebo, fluconazole, and itraconazole solution (OR, 0.49 to 0.54 [95% CI, 0.28 to 0.88]). The incremental cost-effectiveness ratio for itraconazole solution was lower than that for posaconazole (Singapore dollars [SGD] 12,546 versus SGD 26,817 per IFI avoided and SGD 5,844 versus SGD 12,423 per LY saved) for transplant patients. For leukemia patients, itraconazole solution was the dominant strategy. Voriconazole was dominated by posaconazole. All triazole antifungals except itraconazole capsule were effective in preventing IFIs. Posaconazole was more efficacious in reducing IFIs and all-cause deaths than were fluconazole and itraconazole. Both itraconazole solution and posaconazole were cost-effective in the Singapore health care setting.

Posaconazole vs fluconazole or itraconazole for prevention of invasive fungal diseases in patients with acute myeloid leukemia or myelodysplastic syndrome: a cost-effectiveness analysis in an Asian teaching hospital.

BACKGROUND: Posaconazole is superior to fluconazole/itraconazole in preventing invasive fungal diseases (IFDs) in neutropenic patients. Whether the higher cost of posaconazole is offset by decreases in IFDs in a given institute requires cost-effective analysis encompassing the spectrum of IFDs and socioeconomic factors specific to that geographic area. METHODS: This study performed a cost-effective analysis of posaconazole prophylaxis for IFDs in an Asian teaching hospital, employing decision modeling and data of IFDs and medication costs specific to the institute, in neutropenic patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). RESULTS: In the cost-effectiveness analysis, the higher cost of posaconazole was partially offset by a reduction in the cost of treating IFDs that were prevented, resulting in an incremental cost of 125,954 Hong Kong dollars/16,148 USD per IFD avoided. Over a lifetime horizon, assuming same case fatality rate of IFDs in both groups, use of posaconazole results in 0.07 discounted life years saved. This corresponds to an incremental cost of 116,023 HKD/14,875 USD per life year saved. This incremental cost per life year saved in posaconazole prophylaxis fulfilled the World Health Organization defined threshold for cost-effectiveness. CONCLUSION: Posaconazole prophylaxis was cost-effective in Hong Kong.

Cost-benefit Analysis of Posaconazole Versus Fluconazole or Itraconazole as a Primary Antifungal Prophylaxis in High-risk Hematologic Patients: A Propensity Score-matched Analysis.

PURPOSE: Posaconazole is effective for the prophylaxis of invasive fungal infections (IFIs) in patients with acute myeloid leukemia or myelodysplastic syndrome during remission induction chemotherapy. However, a cost-benefit analysis of posaconazole versus fluconazole or itraconazole has not been conducted in Korea. METHODS: We retrospectively reviewed data for all consecutive patients who received primary antifungal prophylaxis during remission induction chemotherapy in our acute myeloid leukemia/myelodysplastic syndrome cohort from December 2010 to November 2013. Patient characteristics and factors known as a risk of IFI were matched with propensity score analysis. We evaluated the medical cost according to the prophylactic antifungal agents (posaconazole vs fluconazole/itraconazole), the development of breakthrough IFIs, and survival status after propensity score matching in a 1:1 ratio. FINDINGS: Of the 419 baseline patients, 100 patients in each group were analyzed after matching. A significant decrease was found in the development of breakthrough proven or probable IFIs (3.0% vs 14.0%; P = 0.009) and the rate of empirical antifungal therapy (EAFT) (12.0% vs 46.0%; P < 0.001) in the posaconazole group. Total in-hospital medical costs per patient were not statistically different between posaconazole and fluconazole/itraconazole prophylaxis. However, the daily medical cost was lower for posaconazole prophylaxis, resulting in a total daily cost savings of $72 (₩79,458) per patient (P = 0.002). In the cases of breakthrough proven/probable IFIs, EAFT, and in-hospital deaths, the total medical costs per patient were significantly higher than in nonproven/probable IFIs, non-EAFT, and in-hospital survivors, as much as $7,916 (₩8,700,758), $4605 (₩5,062,529), and $11,134 (₩12,238,422), respectively. Costs for the antifungal agent used in targeted or empirical therapy were lower in the posaconazole group, resulting in a savings of $697 (₩766,347) per patient (P < 0.001). IMPLICATIONS: Posaconazole appears to be cost beneficial for primary antifungal prophylaxis in high-risk patients with hematologic malignancy, at a single center, in Korea. Cost-benefit is closely related with clinical outcomes, including breakthrough IFI development, EAFT, and survival status.

An update to the cost-effectiveness of posaconazole vs fluconazole or itraconazole in the prevention of invasive fungal disease among neutropenic patients in the United States.

OBJECTIVES: Posaconazole has shown superior clinical efficacy in the prevention of invasive fungal disease (IFD) among neutropenic patients as well as cost-effectiveness in the US healthcare setting vs fluconazole or itraconazole (FLU/ITRA) based on oral suspension formulations of each therapy. This study aims to provide an update on the cost-effectiveness of posaconazole in the current US healthcare setting to reflect bioequivalent tablet formulations of posaconazole and fluconazole, as well as changes in healthcare and drug costs. METHODS: An existing model was used to assess the cost-effectiveness of posaconazole vs FLU/ITRA in the prevention of IFD among patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) and chemotherapy-induced neutropenia. Drug efficacy, mortality related to IFD, and death from other causes were estimated for tablet formulations using data from a randomized clinical trial of oral suspensions based on bioequivalence. IFD treatment costs were updated using the average inflation rate over 8 years (2006-2014) and drug costs were based on 2014 Analysource data. RESULTS: Trial data show a lower IFD probability over 100 days of follow-up with posaconazole compared to standard azole therapy (0.05 vs 0.11). The treatment duration on posaconazole is 29 days compared to 24 days for FLU and 29 days for ITRA. The average cost of prophylaxis is higher in the posaconazole group compared to FLU/ITRA ($4673 vs $353); however, the costs associated with treating the IFD are lower in the posaconazole group compared to FLU/ITRA ($2205 vs $5303). The incremental cost effectiveness ratio of IFD avoided for posaconazole is $18,898 vs FLU/ITRA. CONCLUSIONS: In the current healthcare cost environment where both drug costs and overall IFD treatment costs have increased since 2007, posaconazole tablets are a cost-effective alternative to fluconazole or itraconazole in the prevention of IFD among neutropenic patients with AML and MDS in the US.

Economic evaluation of posaconazole versus fluconazole or itraconazole in the prevention of invasive fungal infection in high-risk neutropenic patients in Sweden.

BACKGROUND: In patients undergoing induction chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), posaconazole has been proven more effective in the prevention of invasive fungal infection (IFI) than fluconazole or itraconazole (standard azoles) The current analysis seeks to estimate the cost effectiveness of prophylactic posaconazole compared with standard azoles in AML or MDS patients with severe chemotherapy-induced neutropenia in Sweden. METHODS: A decision-analytic model was used to estimate life expectancy, costs, and quality-adjusted life-years (QALYs). Efficacy data were derived from a phase III clinical trial. Life expectancy and quality of life data were collected from the literature. A modified Delphi method was used to gather expert opinion on resource use for an IFI. Unit costs were captured from hospital and pharmacy pricelists. A probabilistic sensitivity analysis (PSA) was used to investigate the impact of uncertainty in the model parameters on the cost-effectiveness results. RESULTS: The estimated mean direct cost per patient with posaconazole prophylaxis was 46,893 Swedish kronor (SEK) (€5,387) and SEK50,017 (€5,746) with standard azoles. Prophylaxis with posaconazole resulted in 0.075 QALYs gained compared with standard azoles. At a cost-effectiveness threshold of SEK500,000/QALY the PSA demonstrated a more than 95 % probability that posaconazole is cost effective versus standard azoles for the prevention of IFI in high-risk neutropenic patients in Sweden. CONCLUSION: Given the assumptions, methods, and data used, posaconazole is expected to be cost effective compared with standard azoles when used as antifungal prophylaxis in AML or MDS patients with chemotherapy-induced prolonged neutropenia in Sweden.

Primary prophylaxis of disseminated histoplasmosis in HIV patients in French Guiana: arguments for cost effectiveness.

Histoplasmosis is the first cause of acquired immunodeficiency syndrome (AIDS) and AIDS-related deaths in French Guiana. Cohort data were used to determine whether primary prophylaxis with 100 mg itraconazole for patients with CD4 counts < 150/mm(3) was cost-effective with different scenarios. For a scenario where 12% of patients died, 60% were aware of their human immunodeficiency virus (HIV) infection and adherence was only 50%, primary prophylaxis would prevent 1 death and 9 cases of histoplasmosis for a cost of 36,792 Euros per averted death, 1,533 per life-year saved, 4,415 Euros per averted case, when only counting the costs of itraconazole prophylaxis. Taking into account the total costs of hospitalization showed that primary prophylaxis would allow a savings of 185,178 Euros per year. Even in a scenario of low adherence, primary prophylaxis would be cost-effective in French Guiana, and presumably in the rest of the Guianas and the Amazon.

Cost-effectiveness of primary antifungal prophylaxis with posaconazole versus itraconazole in allogeneic hematopoietic stem cell transplantation.

PURPOSE: To evaluate the cost-effectiveness of posaconazole vs itraconazole in the prevention of invasive fungal infections (IFIs) in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Total hospital-based costs from initial admission for allo-HSCT until day 100 after transplantation were evaluated for 49 patients in whom the clinical efficacy of antifungal prophylaxis with posaconazole vs itraconazole had been previously analyzed and reported. Clinical and economic data were used to determine the incremental costs per IFI avoided and per life-year gained for posaconazole compared with itraconazole. Confidence intervals for the incremental cost-effectiveness ratio (ICER) and a cost-effectiveness acceptability curve were estimated through bootstrapping with the bias-corrected percentile method. RESULTS: According to our analysis, the total cost of allo-HSCT per patient during the 100-day fixed-treatment period was €46,562 in the posaconazole group (n = 33) and €45,080 in the itraconazole group (n = 16). However, the reduction in the incidence of IFI and the improved outcome with posaconazole resulted in a favorable ICER of €11,856 per IFI avoided and €5218 per life-year gained. With the outcomes of the bootstrap procedure, the cost-effectiveness acceptability curve was constructed. Assuming a threshold of €30,000 per life-year gained, the ICER based on life-years gained is acceptable with 75% certainty. LIMITATIONS: This evaluation is based on data from a single-center, non-randomized study. Preference weights or utilities were not available to calculate quality-adjusted life-years. Extra-mural costs were only partially evaluated from a hospital perspective. Indirect costs and economic consequences are not included. CONCLUSIONS: This economic evaluation compared direct medical costs associated with posaconazole or itraconazole treatment; the data suggest that posaconazole may be cost-effective as antifungal prophylaxis during the early high-risk neutropenic period and up to 100 days after allo-HSCT.

A cost-effectiveness analysis of subcutaneous interferon beta-1a 44mcg 3-times a week vs no treatment for patients with clinically isolated syndrome in Sweden.

OBJECTIVE: To assess the cost-effectiveness of subcutaneous interferon (sc IFN) beta-1a 44 mcg 3-times weekly (tiw) vs no treatment at reducing the risk of conversion to multiple sclerosis (MS) in patients with clinically isolated syndrome (CIS) in Sweden. METHODS: A Markov model was constructed to simulate the clinical course of patients with CIS treated with sc IFN beta-1a 44 mcg tiw or no treatment over a 40-year time horizon. Costs were estimated from a societal perspective in 2012 Swedish kronor (SEK). Treatment efficacy data were derived from the REFLEX trial; resource use and quality-of-life (QoL) data were obtained from the literature. Costs and outcomes were discounted at 3%. Sensitivity analyses explored whether results were robust to changes in input values and use of Poser criteria. RESULTS: Using McDonald criteria sc IFN beta-1a was cost-saving and more effective (i.e., dominant) vs no treatment. Gains in progression free life years (PFLYs) and quality-adjusted life-years (QALYs) were 1.63 and 0.53, respectively. Projected cost savings were 270,263 SEK. For Poser criteria cost savings of 823,459 SEK were estimated, with PFLY and QALY gains of 4.12 and 1.38, respectively. Subcutaneous IFN beta-1a remained dominant from a payer perspective. Results were insensitive to key input variation. Probabilistic sensitivity analysis estimated a 99.9% likelihood of cost-effectiveness at a willingness-to-pay threshold of 500,000 SEK/QALY. CONCLUSION: Subcutaneous IFN beta-1a is a cost-effective option for the treatment of patients at high risk of MS conversion. It is associated with lower costs, greater QALY gains, and more time free of MS. LIMITATIONS: The risk of conversion from CIS to MS was extrapolated from 2-year trial data. Treatment benefit was assumed to persist over the model duration, although long-term data to support this are unavailable. Cost and QoL data from MS patients were assumed applicable to CIS patients.

Posaconazole vs fluconazole/itraconazole in the prophylaxis of invasive fungal infections in immunocompromised patients: a cost-effectiveness analysis in Greece.

BACKGROUND: Invasive fungal infections (IFIs) present a major issue in clinical practice, due to their high morbidity and mortality rates. In a pivotal multi-centre, randomized clinical trial, posaconazole prophylaxis prevented IFIs more effectively than did either fluconazole or itraconazole, and improved overall survival. OBJECTIVE: The aim of this study was to perform an economic evaluation of the aforementioned therapeutic strategies for IFI prophylaxis in neutropenic patients, in the Greek healthcare setting. METHOD: A decision analytic model was developed, which described the course of neutropenic patients under posaconazole or standard azole (fluconazole or itraconazole) treatment. Effectiveness data for each treatment regimen were derived from published results of a pivotal, multi-centre, randomized clinical trial. Cost and healthcare resources utilization data depict Greek clinical practice and are derived from official Greek sources, from a third party payer perspective. RESULTS: Prophylaxis with posaconazole resulted in fewer IFIs (0.05 vs 0.11 per patient) compared to treatment with fluconazole or itraconazole, during the first 100 days from initiation of prophylaxis treatment. The cost per avoided IFI with posaconazole was €6455, while the incremental cost per life year gained (LYG) was estimated at €24,196. Extensive sensitivity analyses corroborated the base-case results. Possible limitations of the study are the exclusion of indirect and outpatient costs from the analysis and the inherent uncertainty with regards to the transferability of the clinical efficacy results of the clinical trial to the Greek healthcare setting. CONCLUSIONS: The utilization of posaconazole for prophylaxis of IFIs neutropenic patients is a therapeutic strategy that provides superior clinical efficacy, while being cost-effective compared to alternative therapies.

Adapting a global cost-effectiveness model to local country requirements: posaconazole case study.

BACKGROUND: Many countries have various requirements for local economic analyses to assess the value of a new health technology and/or to secure reimbursement. This study presents a case study of an economic model developed to assess the cost-effectiveness of posaconazole vs standard azole therapy (fluconazole/itraconazole) to prevent invasive fungal infections (IFIs), which was adapted by at least 11 countries. METHODS: Modeling techniques were used to assess the cost-effectiveness of posaconazole vs fluconazole/itraconazole as IFI prophylaxis in patients with acute myelogenous leukemia or myelodysplastic syndromes and chemotherapy-induced neutropenia. For the core model, the probabilities of experiencing an IFI, IFI-related death, and death from other causes were estimated from clinical trial data. Long-term mortality, drug costs, and IFI treatment costs were obtained from secondary sources. Locally changed parameters were probabilities of long-term death and survival, currency, drug costs, health utility, IFI treatment costs, and discount rate. RESULTS: Locally adapted cost-effective modeling studies indicate that prophylaxis with posaconazole, compared with fluconazole/itraconazole, prolongs survival, and, in most countries, is cost-saving. In all countries, the model predicted that prophylaxis with posaconazole would be associated with an increase in life-years, with increases ranging from 0.016-0.1 life-year saved. In all countries, use of the model led to posaconazole being approved by the appropriate reimbursement authority. LIMITATIONS: The study did not have power to detect differences between posaconazole and fluconazole or itraconazole separately. The risk of death after 100 days was assumed to be equal for those who did and did not develop an IFI, and equal probabilities of IFI-related and other death during the trial period were used for both groups. CONCLUSIONS: A core economic model was successfully adapted locally by several countries. The model showed that posaconazole was cost-saving or cost-effective vs fluconazole/itraconazole and led to positive reimbursement listings.

Sporotrichosis.

Sporotrichosis is the most common subcutaneous mycosis. It is usually acquired by traumatic inoculation, and it is caused by one of the species of the Sporothrix schenckii complex. More than 6 species, such as S schenckii sensu stricto, Sporothrix brasiliensis, Sporothrix globosa, Sporothrix mexicana, and Sporothrix albicans, have been identified by molecular techniques. The most common presentation is cutaneous disease, which is classified into fixed and lymphocutaneous forms. Osteoarticular, pulmonary, mucosal, disseminated, and systemic infections are less common and usually occur in immunosuppressed individuals. The diagnosis is suggested by biopsy specimen and confirmed by tissue culture. Itraconazole is considered the treatment of choice, although in some undeveloped countries potassium iodide is still used, owing to its safety and low cost. For systemic or disseminated cases, amphotericin B is the treatment of choice.

Cost-effectiveness of posaconazole versus fluconazole or itraconazole in the prevention of invasive fungal infections among high-risk neutropenic patients in Spain.

BACKGROUND: We evaluated the cost-effectiveness of posaconazole compared with standard azole therapy (SAT; fluconazole or itraconazole) for the prevention of invasive fungal infections (IFI) and the reduction of overall mortality in high-risk neutropenic patients with acute myelogenous leukaemia (AML) or myelodysplastic syndromes (MDS). The perspective was that of the Spanish National Health Service (NHS). METHODS: A decision-analytic model, based on a randomised phase III trial, was used to predict IFI avoided, life-years saved (LYS), total costs, and incremental cost-effectiveness ratio (ICER; incremental cost per LYS) over patients' lifetime horizon. Data for the analyses included life expectancy, procedures, and costs associated with IFI and the drugs (in euros at November 2009 values) which were obtained from the published literature and opinions of an expert committee. A probabilistic sensitivity analysis (PAS) was performed. RESULTS: Posaconazole was associated with fewer IFI (0.05 versus 0.11), increased LYS (2.52 versus 2.43), and significantly lower costs excluding costs of the underlying condition (€6,121 versus €7,928) per patient relative to SAT. There is an 85% probability that posaconazole is a cost-saving strategy compared to SAT and a 97% probability that the ICER for posaconazole relative to SAT is below the cost per LYS threshold of €30,000 currently accepted in Spain. CONCLUSIONS: Posaconazole is a cost-saving prophylactic strategy (lower costs and greater efficacy) compared with fluconazole or itraconazole in high-risk neutropenic patients.

Impact of first-line antifungal agents on the outcomes and costs of candidemia.

Candida species are the leading causes of invasive fungal infection among hospitalized patients and are responsible for major economic burdens. The goals of this study were to estimate the costs directly associated with the treatment of candidemia and factors associated with increased costs, as well as the impact of first-line antifungal agents on the outcomes and costs. A retrospective study was conducted in a sample of 199 patients from four university-affiliated tertiary care hospitals in Korea over 1 year. Only costs attributable to the treatment of candidemia were estimated by reviewing resource utilization during treatment. Risk factors for increased costs, treatment outcome, and hospital length of stay (LOS) were analyzed. Approximately 65% of the patients were treated with fluconazole, and 28% were treated with conventional amphotericin B. The overall treatment success rate was 52.8%, and the 30-day mortality rate was 47.9%. Hematologic malignancy, need for mechanical ventilation, and treatment failure of first-line antifungal agents were independent risk factors for mortality. The mean total cost for the treatment of candidemia was $4,743 per patient. Intensive care unit stay at candidemia onset and antifungal switch to second-line agents were independent risk factors for increased costs. The LOS was also significantly longer in patients who switched antifungal agents to second-line drugs. Antifungal switch to second-line agents for any reasons was the only modifiable risk factor of increased costs and LOS. Choosing an appropriate first-line antifungal agent is crucial for better outcomes and reduced hospital costs of candidemia.

Cost-effectiveness of posaconazole versus fluconazole for prevention of invasive fungal infections in U.S. patients with graft-versus-host disease.

PURPOSE: The results of a pharmacoeconomic study of the cost-effectiveness of posaconazole versus fluconazole in preventing invasive fungal infections (IFIs) in patients with graft-versus-host disease (GVHD) are reported. METHODS: The results of a randomized clinical trial suggested that posaconazole may be as effective as fluconazole for the prevention of IFIs in recipients of allogeneic cell transplants who develop severe GVHD and that posaconazole may be superior to fluconazole in reducing IFI-related deaths. Using published data from that trial and data from secondary sources, an economic model was developed to estimate the costs, IFIs avoided, and life-years saved with posaconazole versus fluconazole therapy. The results of the modeled 112-day treatment simulation were extrapolated to a lifetime horizon. RESULTS: In the modeled simulation, posaconazole therapy was associated with a lower probability of IFI development (0.05 versus 0.09), increased discounted life-years (7.87 life-years versus 7.66 life-years), and higher discounted costs per patient ($8,860 versus $5,710 in 2006 U.S. dollars) relative to fluconazole therapy. The estimated incremental cost-effectiveness of posaconazole versus fluconazole for IFI prophylaxis was $85,300 per IFI avoided and $15,300 per life-year saved. A sensitivity analysis indicated a 90% probability that the use of posaconazole for this purpose would be cost-effective at a threshold of $50,000 per life-year saved. CONCLUSION: Posaconazole is in the range of currently accepted criteria for cost- effectiveness relative to fluconazole for the prevention of IFIs among patients with GVHD.

[Cost effectiveness of posaconazole versus fluconazole/itraconazole in the prophylactic treatment of invasive fungal infections in Mexico]. / Costo efectividad de posaconazol versus fluconazol/itraconazol en el tratamiento profiláctico de las infecciones fúngicas invasivas en México.

UNLABELLED: Cost effectiveness of posaconazole versus fluconazole/itraconazole therapy in the prophylaxis against invasive fungal Infections among high-risk neutropenic patients in Mexico. OBJECTIVE: To estimate the cost effectiveness and long-term combined effects of Posaconazole versus fluconazole/itraconazole (standard azole) therapy in the prophylaxis against invasive fungal Infections among high-risk neutropenic patients in Mexico. METHODS: A previously validated Markov model was used to compare the projected lifetime costs and effects of two theoretical groups of patients, one receiving Posaconazole and the other receiving standard azole. The model estimates total costs, numbers of IFIs, and QALY per patient in each prophylaxis group. To extrapolate trial results to a lifetime horizon, the model was extended with one-month Markov cycles in which mortality risk is specific to the underlying disease. Data on the probabilities of IFI were obtained from Study Protocol PO1899. Drug costs were taken from average wholesale drug reports for 2009. Cost and health effects were discounted at 5% according to the Mexican guideline. The analysis was conducted from the Mexican healthcare perspective using 2008 unit cost prices. RESULTS: Our model projects an accumulated cost to the Mexican healthcare system per patient receiving the Posaconazol regimen of $US 5,634 compared to $US 7,463 for the standard azole regimen. The accumulated discounted effect is 3.13 LY or 2.25 QALYs per patient receiving Posaconazol, compared to 2.96 LY or 2.13 QALYs per patient receiving standard azole. Posaconazol remained the dominant strategy across each scenario. Probabilistic sensitivity analysis tested numerous assumptions about the model cost and efficacy parameters and found that the results were robust to most changes. CONCLUSION: Posaconazole provides modest incremental benefits compared with standard azole therapy in the prophylaxis against IFIs among high-risk neutropenic patients. Routine Posaconazole use appears a cost saving when the likelihood of IFIs or the cost of treatment medications is high.