A cost-effectiveness analysis of the use of oral ibrexafungerp versus fluconazole for acute vulvovaginal candidiasis in the UK NHS primary care service.

BACKGROUND: Vulvovaginal Candidiasis (VVC) is a fungal infection causing inflammation of the vagina and/or the vulva. Symptoms include itching, irritation, and discharge. VVC presents commonly across primary care and, despite its mild symptoms, carries psychological burden and has a significant impact on women's quality of life. UK guidelines support treatment via oral or topical azole antifungal agents. Recent evidence attests to the superiority of novel non-azole antifungals. Thus, rigorous financial assessment of both antifungals is necessary for optimal VVC treatment allocation in UK primary care. AIM: To evaluate the cost-effectiveness of ibrexafungerp against the gold standard fluconazole as first-line treatment of VVC within the NHS. METHOD: A systematic review on the efficacy of ibrexafungerp and fluconazole in acute VVC was conducted. Cost-effectiveness analysis was initiated using health outcome data from the DOVE trial, a Phase 2 RCT. Costs in pound sterling were ascertained in monetary units, and effectiveness determined as reduced need for follow-up medication. RESULTS: An incremental cost-effectiveness ratio of £2185.74 was determined. This suggests oral ibrexafungerp being largely more costly yet slightly more effective than fluconazole, and thus has unfavourable net benefit. Two sensitivity analyses were conducted considering follow-up medication combination and market price, which provided confidence in the calculated cost-effectiveness ratio. CONCLUSION: This analysis highlights fluconazole's cost-effectiveness in current UK guidelines and favourability.

Leave no one behind: response to new evidence and guidelines for the management of cryptococcal meningitis in low-income and middle-income countries.

In 2018, WHO issued guidelines for the diagnosis, prevention, and management of HIV-related cryptococcal disease. Two strategies are recommended to reduce the high mortality associated with HIV-related cryptococcal meningitis in low-income and middle-income countries (LMICs): optimised combination therapies for confirmed meningitis cases and cryptococcal antigen screening programmes for ambulatory people living with HIV who access care. WHO's preferred therapy for the treatment of HIV-related cryptococcal meningitis in LMICs is 1 week of amphotericin B plus flucytosine, and the alternative therapy is 2 weeks of fluconazole plus flucytosine. In the ACTA trial, 1-week (short course) amphotericin B plus flucytosine resulted in a 10-week mortality of 24% (95% CI -16 to 32) and 2 weeks of fluconazole and flucytosine resulted in a 10-week mortality of 35% (95% CI -29 to 41). However, with widely used fluconazole monotherapy, mortality because of HIV-related cryptococcal meningitis is approximately 70% in many African LMIC settings. Therefore, the potential to transform the management of HIV-related cryptococcal meningitis in resource-limited settings is substantial. Sustainable access to essential medicines, including flucytosine and amphotericin B, in LMICs is paramount and the focus of this Personal View.

Rapid species identification of Candida directly from blood culture broths by Sepsityper-MALDI-TOF mass spectrometry: impact on antifungal therapy.

Rapid identification of Candida species facilitates pathogen-directed therapy with either fluconazole or an echinocandin. METHOD: We applied Sepsityper matrix-assisted laser desorption ionisation time of flight mass spectrometry (MALDI-TOF-MS) technology on positive blood culture broths for rapid species identification. RESULTS: Of the 74 patients with candidaemia, 25 had the species identified on the day of the positive blood culture directly from the broth (rapid identification group) while the remaining 49 had the species identified from culture (conventional identification group). Three (13.6%) out of 22 treated patients in the rapid identification group received echinocandin compared to 20/45 (44.4%) in the conventional identification group. The appropriateness of therapy was 90.9% in the rapid identification group and 62.2% in the conventional identification group (p = 0.01). Cost savings were more than £10,000 in the first three days of treatment. CONCLUSION: Sepsityper-MALDI-TOF-MS is a useful tool in supporting antifungal stewardship programmes.

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 de-escalation from micafungin versus escalation from fluconazole for invasive candidiasis in China.

AIMS: Guidelines on treating invasive candidiasis recommend initial treatment with a broad-spectrum echinocandin (e.g. micafungin), then switching to fluconazole if isolates prove sensitive (de-escalation strategy). This study aimed to evaluate the cost-effectiveness of de-escalation from micafungin vs escalation from fluconazole from a Chinese public payers perspective. MATERIALS AND METHODS: Cost-effectiveness was estimated using a decision analytic model, in which patients begin treatment with fluconazole 400 mg/day (escalation) or micafungin 100 mg/day (de-escalation). From Day 3, when susceptibility results are available, patients are treated with either fluconazole (if isolates are fluconazole-sensitive/dose-dependent) or micafungin (if isolates are resistant). The total duration of (appropriate) treatment is 14 days. Model inputs are early (Day 3) and end-of-treatment mortality rates, treatment success rates, and health resource utilization. Model outputs are costs of health resource utilization over 42 days, incremental cost per life-year, and incremental cost per quality-adjusted life-year (QALY) over a lifetime horizon. RESULTS: In the base-case analysis, the de-escalation strategy was associated with longer survival and higher treatment success rates compared with escalation, at a lower overall cost (-¥1,154; -175 United States Dollars). Life-years and QALYs were also better with de-escalation. Thus, this strategy dominated the escalation strategy for all outcomes. In a probabilistic sensitivity analysis, 99% of 10,000 simulations were below the very cost-effective threshold (1 × gross domestic product). LIMITATIONS: The main limitation of the study was the lack of real-world input data for clinical outcomes on treatment with micafungin in China; data from other countries were included in the model. CONCLUSION: A de-escalation strategy is cost-saving from the Chinese public health payer perspective compared with escalation. It improves outcomes and reduces costs to the health system by reducing hospitalization, due to an increase in the proportion of patients receiving appropriate treatment.

Fluconazole versus mould-active triazoles for primary antifungal prophylaxis in adult patients with acute lymphoblastic leukemia: clinical outcome and cost-effectiveness analysis.

This study evaluated the clinical and cost-effectiveness of prophylactic use of fluconazole versus mould-active triazoles (voriconazole and posaconazole) in adult patients with acute lymphoblastic leukemia (ALL). A decision analytical model was developed with inputs from a 7-year retrospective study (2009-2016) of 103 consecutive adult patients with ALL who received antifungal prophylaxis. Information on the administration of antifungal agents, clinical outcomes, and costs were collected. One-way sensitivity analyses and probabilistic sensitivity analysis were performed. The mould-active triazoles group was associated with higher life-years (3.71 vs 3.59) and lower total costs (US$4886 vs US$5722) per patient compared with fluconazole. One-way sensitivity analyses revealed that varying all of the key variables in the model did not affect the robustness of the results. Probabilistic sensitivity analysis demonstrated that mould-active triazoles had a probability of 77.1 and 90.1% of providing a dominant and cost-effective option relative to fluconazole, respectively. Mould-active triazoles should be regarded as preferable to fluconazole as the first-line prophylactic for adult patients with ALL accompanied by uncommon severe vinca alkaloid-induced neurotoxicity. However, the results reported here should be interpreted with caution owing to the observational nature of the data.

Cost-effectiveness of posaconazole tablets versus fluconazole as prophylaxis for invasive fungal diseases in patients with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: The cost-effectiveness of posaconazole oral suspension versus fluconazole capsules for the prophylaxis of invasive fungal diseases (IFDs) in immunosuppressed allogeneic hematopoietic stem cell transplantation (HSCT) recipients has already been proven. Now, a new solid oral tablet formulation for posaconazole has been developed with improved bioavailability, allowing a reduced daily dosage that can be taken independently of food intake. However, the efficacy of this new formulation should be evaluated since it is associated with a higher cost than the posaconazole oral suspension. OBJECTIVES: To evaluate the cost-effectiveness of solid oral tablets of posaconazole versus fluconazole capsules for the prophylaxis of IFDs in allogeneic HSCT recipients with graft-versus-host disease (GVHD) in Spain. METHODOLOGY: A mathematical model comparing the efficacy and costs of posaconazole versus fluconazole was adapted to the Spanish National Healthcare System. Clinical data were obtained from the pivotal clinical trial of posaconazole oral suspension for allogeneic HSCT recipients, while pharmacological costs and use of resources were obtained from national sources. Deterministic and probabilistic sensitivity analyses (PSA), as well as two alternative scenarios, were run to evaluate the robustness of the results under varying input values. RESULTS: Posaconazole tablets reduced the number of IFD events and enhanced overall survival, while maintaining a controlled budget. When compared to fluconazole, it was found to be a cost-effective alternative, with an incremental cost-effectiveness ratio of €13,193/life years gained. The PSA showed that posaconazole remained cost-effective in 74.6% of the cases, while alternatives scenarios yielded similar results as the base case. CONCLUSIONS: Posaconazole tablets are a cost-effective alternative to fluconazole and may show better results than the oral suspension formulation.

Cost Effectiveness of Candida Polymerase Chain Reaction Detection and Empirical Antifungal Treatment among Patients with Suspected Fungal Peritonitis in the Intensive Care Unit.

BACKGROUND: Mortality from intra-abdominal candidiasis in intensive care units (ICUs) is high. It takes many days for peritoneal-fluid fungal culture to become positive, and the recommended empirical antifungal therapy involves excessive costs. Polymerase chain reaction (PCR) should produce results more rapidly than fungal culture. OBJECTIVES: To perform a cost-effectiveness analysis of the combination of several diagnostic and therapeutic strategies to manage Candida peritonitis in non-neutropenic adult patients in ICUs. METHODS: We constructed a decision tree model to evaluate the cost effectiveness. Cost and effectiveness were taken into account in a 1-year time horizon and from the French National Health Insurance perspective. Six strategies were compared: fluconazole or echinocandin as an empirical therapy, plus diagnosis by fungal culture or detection by PCR of all Candida species, or use of PCR to detect most fluconazole-resistant Candida species (i.e., Candida krusei and Candida glabrata). RESULTS: The use of fluconazole empirical treatment and PCR to detect all Candida species is more cost effective than using fluconazole empirical treatment without PCR (incremental cost-effectiveness ratio of €40,055/quality-adjusted life-year). Empirical treatment with echinocandin plus PCR to detect C. krusei and C. glabrata is the most effective strategy, but has an incremental cost-effectiveness ratio of €93,776/quality-adjusted life-year. If the cost of echinocandin decreases, then strategies involving PCR plus empirical echinocandin become more cost-effective. CONCLUSIONS: Detection by PCR of all Candida species and of most fluconazole-resistant Candida species could improve the cost-effectiveness of fluconazole and echinocandin given to non-neutropenic patients with suspected peritoneal candidiasis in ICUs.

Choosing Optimal Antifungal Agents To Prevent Fungal Infections in Nonneutropenic Critically Ill Patients: Trial Sequential Analysis, Network Meta-analysis, and Pharmacoeconomic Analysis.

The use of antifungal interventions in critically ill patients prior to invasive fungal infection (IFI) being microbiologically confirmed and the preferred drug are still controversial. A systematic literature search was performed to identify randomized controlled trials (RCTs) that compared untargeted antifungal treatments applied to nonneutropenic critically ill patients. The primary outcomes were all-cause mortality and proven IFI rates. A random-effects model was used with trial sequential analyses (TSA), a network meta-analysis (NMA) was conducted to obtain indirect evidence, and a cost-effectiveness analysis using a decision-analytic model was completed from the patient perspective over a lifetime horizon. In total, 19 RCTs involving 2,556 patients (7 interventions) were included. Untargeted antifungal treatment did not significantly decrease the incidence of all-cause mortality (odds ratio [OR] = 0.89, 95% confidence interval [95%CI] = 0.70 to 1.14), but it did reduce the incidence of proven IFI (OR = 0.45, 95%CI = 0.29 to 0.71) relative to placebo/no intervention. The TSA showed that there was sufficient evidence supporting these findings. In the NMA, the only significant difference found for both primary outcomes was between fluconazole and placebo/no intervention in preventing proven IFI (OR = 0.35, 95%CI = 0.19 to 0.65). Based on drug and hospital costs in China, the incremental cost-effectiveness ratios per life-year saved for fluconazole, caspofungin, and micafungin relative to placebo/no intervention corresponded to US$889, US$9,994, and US$10,351, respectively. Untargeted antifungal treatment significantly reduced proven IFI rates in nonneutropenic critically ill patients but with no mortality benefits relative to placebo/no intervention. Among the well-tolerated antifungals, fluconazole remains the only one that is effective for IFI prevention and significantly cheaper than echinocandins.

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.

Pharmacoeconomic analysis of antifungal therapy for primary treatment of invasive candidiasis caused by Candida albicans and non-albicans Candida species.

BACKGROUND: Cost-effectiveness studies of echinocandins for the treatment of invasive candidiasis, including candidemia, are rare in Asia. No study has determined whether echinocandins are cost-effective for both Candida albicans and non-albicans Candida species. There have been no economic evaluations that compare non-echinocandins with the three available echinocandins. This study was aimed to assess the cost-effectiveness of individual echinocandins, namely caspofungin, micafungin, and anidulafungin, versus non-echinocandins for C. albicans and non-albicans Candida species, respectively. METHODS: A decision tree model was constructed to assess the cost-effectiveness of echinocandins and non-echinocandins for invasive candidiasis. The probability of treatment success, mortality rate, and adverse drug events were extracted from published clinical trials. The cost variables (i.e., drug acquisition) were based on Taiwan's healthcare system from the perspective of a medical payer. One-way sensitivity analyses and probability sensitivity analyses were conducted. RESULTS: For treating invasive candidiasis (all species), as compared to fluconazole, micafungin and caspofungin are dominated (less effective, more expensive), whereas anidulafungin is cost-effective (more effective, more expensive), costing US$3666.09 for each life-year gained, which was below the implicit threshold of the incremental cost-effectiveness ratio in Taiwan. For C. albicans, echinocandins are cost-saving as compared to non-echinocandins. For non-albicans Candida species, echinocandins are cost-effective as compared to non-echinocandins, costing US$652 for each life-year gained. The results were robust over a wide range of sensitivity analyses and were most sensitive to the clinical efficacy of antifungal treatment. CONCLUSIONS: Echinocandins, especially anidulafungin, appear to be cost-effective for invasive candidiasis caused by C. albicans and non-albicans Candida species in Taiwan.

Cost-effectiveness analysis of anidulafungin vs fluconazole for the treatment of invasive candidiasis (IC) in Turkey.

Anidulafungin has been shown to be non-inferior to, and possibly more efficacious, than fluconazole in treating patients with invasive candidiasis (IC). This study aimed to determine the cost-effectiveness of anidulafungin vs fluconazole for treatment of IC in the Turkish setting. A decision analytic model was constructed to depict downstream economic consequences of using anidulafungin or fluconazole for treatment of IC in the Turkish hospitals. Transition probabilities (ie treatment success, observed or indeterminate treatment failures) were obtained from a published randomised clinical trial. Cost inputs were from the latest Turkish resources. Data not available in the literature were estimated by expert panels. Sensitivity analyses were performed to assess the robustness of the model outcome. While anidulafungin [TL 17 171 (USD 4589)] incurred a higher total cost than fluconazole [TL 8233 (USD 2200) per treated patient, treatment with anidulafungin was estimated to save an additional 0.58 life-years, with an incremental cost-effectiveness ratio of TL 15 410 (USD 4118) per life-years saved. Drug acquisition cost and hospitalisation were the main cost drivers for anidulafungin and fluconazole arms respectively. The model findings were robust over a wide range of input variables except for anidulafungin drug cost. Anidulafungin appears to be a cost-effective therapy in treating IC from the Turkish hospital perspective.

Recent advances in AIDS-related cryptococcal meningitis treatment with an emphasis on resource limited settings.

INTRODUCTION: Recent advances in the treatment and prevention of cryptococcal meningitis have the potential to decrease AIDS-related deaths. Areas covered: Targeted screening for asymptomatic cryptococcal antigenemia in persons with AIDS is a cost effective method for reducing early mortality in patients on antiretroviral therapy. For persons with symptomatic cryptococcal meningitis, optimal initial management with amphotericin and flucytosine improves survival compared to alternative therapies; however, amphotsericin is difficult to administer and flucytosine has not been available in middle or low income countries, where cryptococcal meningitis is most prevalent. Expert commentary: Improved care for cryptococcal meningitis patients in resource-limited settings is possible, and new treatment possibilities are emerging.

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.

Cryptococcal Meningitis Treatment Strategies Affected by the Explosive Cost of Flucytosine in the United States: A Cost-effectiveness Analysis.

BACKGROUND: In the United States, cryptococcal meningitis causes approximately 3400 hospitalizations and approximately 330 deaths annually. The US guidelines recommend treatment with amphotericin B plus flucytosine for at least 2 weeks, followed by fluconazole for a minimum of 8 weeks. Due to generic drug manufacturer monopolization, flucytosine currently costs approximately $2000 per day in the United States, with a 2-week flucytosine treatment course costing approximately $28 000. The daily flucytosine treatment cost in the United Kingdom is approximately $22. Cost-effectiveness analysis was performed to determine the value of flucytosine relative to alternative regimens. METHODS: We estimated the incremental cost-effectiveness ratio (ICER) of 3 cryptococcal induction regimens: (1) amphotericin B deoxycholate for 4 weeks; (2) amphotericin and flucytosine (100 mg/kg/day) for 2 weeks; and (3) amphotericin and fluconazole (800 mg/day) for 2 weeks. Costs of care were calculated using 2015 US prices and the medication costs. Survival estimates were derived from a randomized trial and scaled relative to published US survival data. RESULTS: Cost estimates were $83 227 for amphotericin monotherapy, $75 121 for amphotericin plus flucytosine, and $44 605 for amphotericin plus fluconazole. The ICER of amphotericin plus flucytosine was $23 842 per quality-adjusted life-year. CONCLUSIONS: Flucytosine is currently cost-effective in the United States despite a dramatic increase in price in recent years. Combination therapy with amphotericin and flucytosine is the most attractive treatment strategy for cryptococcal meningitis, though the rising price may be creating access issues that will exacerbate if the trend of profiteering continues.

Cost Analysis of Fluconazole Prophylaxis for Prevention of Neonatal Invasive Candidiasis.

BACKGROUND: Fluconazole prophylaxis (FP) in premature infants is well studied and has been shown to decrease invasive candidiasis (ICs). IC in neonates has significant financial costs; determining the cost-benefit of FP may provide additional justification for targeting high-risk neonates. We aimed to determine the IC rate in premature infants at which FP is cost-beneficial. METHODS: A decision tree cost-analysis model using cost of FP related to costs associated with IC was used. We searched PubMed for all papers that used intravenous FP and reported rates of IC in very low birth weight neonates. Average IC rates in those who received FP (2.0%; range, 0-6.1%) and in those who did not receive FP (9.2%; range, 0-20.5%) were used. Incremental hospital costs because of IC and for FP were retrieved from the literature. Sensitivity analysis was performed to determine the incremental cost of FP across the range of published IC rates. RESULTS: The average cost per patient attributed to IC in patients receiving FP was $785 versus $2617 in those not receiving FP. Sensitivity analysis demonstrates the rate of IC would need to be <2.8% for FP to lose its cost-benefit. In Monte Carlo simulation, targeting infants <1000 g would lead to $50,304,333 in cost savings per year in the United States. CONCLUSIONS: FP provides a cost-advantage across most IC rates seen in the youngest premature infants. Using a rate of 2.8% for their individual high-risk neonatal intensive care unit patients, providers can determine if FP is cost-beneficial in determining for whom to provide IC prophylaxis.

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.

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.

Cost-effectiveness analysis of anidulafungin for the treatment of candidaemia and other forms of invasive candidiasis.

BACKGROUND: Candidaemia and other forms of invasive candidiasis (C/IC) in the intensive care unit are challenging conditions that are associated with high rates of mortality. New guidelines from the European Society for Clinical Microbiology and Infectious Diseases strongly recommend echinocandins for the first-line treatment of C/IC. Here, a cost-effectiveness model was developed from the United Kingdom perspective to examine the costs and outcomes of antifungal treatment for C/IC based on the European Society for Clinical Microbiology and Infectious Diseases guidelines. METHODS: Costs and treatment outcomes with the echinocandin anidulafungin were compared with those for caspofungin, micafungin and fluconazole. The model included non-neutropenic patients aged ≥16 years with confirmed C/IC who were receiving intravenous first-line treatment. Patients were categorised as either a clinical success or failure (patients with persistent/breakthrough infection); successfully treated patients switched to oral therapy, while patients categorised as clinical failures switched to a different antifungal class. Other inputs were all-cause mortality at 6 weeks, costs of treatment-related adverse events and other medical resource utilisation costs. Resource use was derived from the published literature and from discussion with clinical experts. Drug-acquisition/administration costs were taken from standard United Kingdom costing sources. RESULTS: The model indicated that first-line anidulafungin could be considered cost-effective versus fluconazole (incremental cost-effectiveness ratio £813 per life-year gained) for the treatment of C/IC. Anidulafungin was cost-saving versus caspofungin and micafungin due to lower total costs and a higher rate of survival combined with a higher probability of clinical success. DISCUSSION: European Society for Clinical Microbiology and Infectious Diseases guidelines recommend echinocandins for the first-line treatment of C/IC; our model indicated that anidulafungin marries clinical effectiveness and cost-effectiveness. CONCLUSIONS: From the United Kingdom perspective, anidulafungin was cost-effective compared with fluconazole for the treatment of C/IC and was cost-saving versus the other echinocandins.

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.