[Standardization of Hypnotic Agents for Prevention of Falls: A Pharmacoeconomic Study].

To reduce the number of falls caused by hypnotic agents, the standardization of insomnia treatment was carried out at Yamaguchi University Hospital from April 2019. There were concerns that medical costs would increase due to the selected medicines-suvorexant and eszopiclone-being more expensive than conventional benzodiazepines. In this study, the standardization of insomnia treatment was evaluated by pharmacoeconomics. The costs of the hypnotic agents was considered, as was the cost of examination/treatment following falls. Effectiveness was evaluated as the incidence of falls within 24 hours of taking hypnotic agents. This analysis took the public healthcare payer's perspective. Propensity score matching based on patient background, showed that, per hospitalization the medicine costs of the recommended group increased by 1,020 yen, however, the examination/treatment costs following falls decreased by 487 yen when compared with the non-recommended group. Overall, the recommended group incurred costs of 533 yen more per hospitalization for patients prescribed hypnotic agents compared to the non-recommended group, but the incidence of falls for the recommended group was significantly lower than that in the non-recommended group (1.9% vs. 6.3%; p<0.01). These results suggest that in order to prevent the incidence of falls by 1 case, it is necessary to increase costs by 12,086 yen which is the subthreshold cost for switching to the recommended medicine as standardization. The selection of recommended medicines may be a cost-effectiveness option compared with non-recommended medicines.

Reimbursement of innovative pharmaceuticals in English and Spanish hospitals-The example of isavuconazole.

BACKGROUND: Kron et al (Mycoses, 64, 2021, 86) found cost savings for the use of the innovative pharmaceutical isavuconazole in the inpatient setting in Germany (Bismarck-based healthcare system). Little is known about the reimbursement of innovative pharmaceuticals in the inpatient setting of Beveridge-based healthcare systems. OBJECTIVES: The aim of this study was to evaluate the market access process and reimbursement of isavuconazole, exemplary for innovative pharmaceuticals, in England and Spain. PATIENTS/METHODS: Market access processes of both countries were described. Focussing on typical patient clusters for isavuconazole treatment, reimbursement data regarding inpatients with (i) allogeneic haematopoietic stem cell transplantation or (ii) acute myeloid leukaemia was considered. Data were publicly available and of high topicality (England 2020/2021, Spain 2018). Discounting and a currency conversion to Euro were applied. RESULTS: This study showed that market access processes of both countries are broadly similar. Further, full reimbursement of isavuconazole as an innovative pharmaceutical may lead to reduction in resource utilisation. Without medication costs, isavuconazole can thus result in cost savings for both patient clusters due to a reduction in length of stay. CONCLUSIONS: Expenses for innovative pharmaceuticals may be balanced or even lead to cost savings due to a reduction in length of stay. The latter contributes to a greater patient benefit. For both healthcare system, the analyses highlighted drugs' cost-effectiveness and assessing its added value into reimbursement decisions is highly relevant.

Principal-agent theory-based cost and reimbursement structures of isavuconazole treatment in German hospitals.

BACKGROUND: Isavuconazole (ISA) is a frequently used antifungal agent for the treatment of invasive fungal diseases (IFDs). However, hospital reimbursement data for ISA is limited. OBJECTIVES: The primary objective of this study was to analyse the different perspectives of relevant stakeholders and the (dis)incentives for the administration of ISA in Germany. To that aim, the health economic effects of using ISA from a hospital management perspective were analysed. PATIENTS/METHODS: Based on principal-agent theory (PAT), the perspectives of (a) the patient (principal) as well as (b) physicians, (c) pharmacists and iv. hospital managers (all agents) were analysed. For the evaluation of the cost-containment and reimbursement strategies of ISA, the German diagnosis-related group (G-DRG) system was used. RESULTS: Hospitals individually negotiating additional payments for innovative treatment procedures (zusatzentgelte [ZE]) within the G-DRG system is a key element of hospital management for the reduction of total healthcare expenditure. Our analysis demonstrated the beneficial role of ISA in healthcare resource utilisation, primarily due to a shortened overall length of hospital stay. Depending on underlying disease, coded G-DRG and ISA formulation, large differences in total reimbursement and the amount of ZE was shown. The PAT demonstrated disincentives for hospital managers to use innovative drugs. CONCLUSIONS: Based on the PAT, beneficial, detrimental and indifferent perspectives of different stakeholders regarding the usage of ISA were shown. A reduction of bureaucratic hurdles is needed in Germany for the extension of effective and innovative antifungal treatment strategies with ISA.

The cost-effectiveness of isavuconazole compared to the standard of care in the treatment of patients with invasive fungal infection prior to differential pathogen diagnosis in the United Kingdom.

Aims: To estimate the cost-effectiveness of isavuconazole compared with the standard of care, voriconazole, for the treatment of patients with invasive fungal infection disease when differential diagnosis of the causative pathogen has not yet been achieved at treatment initiation.Materials and methods: The economic model was developed from the perspective of the UK National Health Service (NHS) and used a decision-tree approach to reflect real-world treatment of patients with invasive fungal infection (IFI) prior to differential pathogen diagnosis. It was assumed that 7.8% of patients with IFI prior to differential pathogen diagnosis at treatment initiation actually had mucormycosis, and confirmation of pathogen identification was achieved for 50% of all patients during treatment. To extrapolate to a lifetime horizon, the model considered expected survival based on the patients' underlying condition. The model estimated the incremental costs (costs of drugs, laboratory analysis, hospitalization, and management of adverse events) and clinical outcomes (life-years (LYs) and quality-adjusted life-years (QALYs)) of first-line treatment with isavuconazole compared with voriconazole. The robustness of the results was assessed by conducting deterministic and probabilistic sensitivity analyses.Results: Isavuconazole delivered 0.48 more LYs and 0.39 more QALYs per patient at an incremental cost of £3,228, compared with voriconazole in the treatment of patients with IFI prior to differential pathogen diagnosis. This equates to an incremental cost-effectiveness ratio (ICER) of £8,242 per additional QALY gained and £6,759 per LY gained. These results were driven by a lack of efficacy of voriconazole in mucormycosis. Results were most sensitive to the mortality of IA patients and treatment durations.Conclusions: At a willingness to pay (WTP) threshold of £30,000 per additional QALY, the use of isavuconazole for the treatment of patients with IFI prior to differential pathogen diagnosis in the UK can be considered a cost-effective allocation of healthcare resources compared with voriconazole.

Second-line treatment with lesinurad and allopurinol versus febuxostat for management of hyperuricemia: a cost-effectiveness analysis for Spanish patients.

INTRODUCTION/OBJECTIVES: Lesinurad, in combination with allopurinol, has been approved for treatment of patients with gout which do not reach therapeutic serum urate target with xanthine oxidase inhibitors monotherapy. The study aimed to assess the incremental cost-effectiveness ratio of adding lesinurad to allopurinol as second-line therapy, compared to febuxostat for patients with gout in Spain. METHOD: A Markov model representing disease evolution was used to estimate the lifetime accumulated cost and benefits in terms of quality-adjusted-life-year (QALY). Patients could either continue with second-line treatment with lesinurad (200 mg/daily) plus allopurinol (400 mg/daily) or febuxostat (80 mg/daily) switch to allopurinol monotherapy (271 mg/daily) in case of intolerance or discontinue treatment. The treatment's efficacy captured in the transition probabilities between health states were derived from CLEAR and EXCEL trials. Quality of life related to gout severity and flare frequency was considered by means of utilities. The total cost estimation (€, 2019) included drug acquisition cost, disease monitoring, and flare management cost. Unitary local costs derived from databases and literature. A 3% annual discount rate was applied for cost and outcomes. RESULTS: Lesinurad plus allopurinol provided higher QALYs (14.79) than febuxostat (14.69). Total accrued cost/patient was lower with lesinurad and allopurinol (€50,631.51) versus febuxostat (€56,698.64). Lesinurad plus allopurinol resulted more effective and less costly (dominant option) versus febuxostat. CONCLUSIONS: Lesinurad plus allopurinol therapy compared with febuxostat seems an effective option for the management of hyperuricemia in patients who did not reach serum urate target to previous allopurinol monotherapy, associated to cost-savings for the Spanish Health System.Key Points• Lesinurad, in combination with allopurinol, has been recently authorized as second-line treatment of hyperuricemia in gout patients.• Lesinurad plus allopurinol provided higher effectiveness in terms of quality-adjusted-life-years (14.79) than febuxostat (14.69).• Lesinurad plus allopurinol resulted less costly (total cost/per patient) compared with febuxostat.• Lesinurad plus allopurinol resulted a dominant option compared with febuxostat.

Isavuconazole to prevent invasive fungal infection in immunocompromised adults: Initial experience at an academic medical centre.

OBJECTIVE: To evaluate clinical and economic outcomes associated with the use of isavuconazole as antifungal prophylaxis in high-risk immunocompromised patients. PATIENTS/METHODS: Retrospective, single-centre cohort study of patients who received isavuconazole prophylaxis. Outcomes assessed included breakthrough IFI, early discontinuation of isavuconazole for any reason and antifungal prophylaxis prescribed at discharge. The impact on inpatient drug expenditure was evaluated using current isavuconazole and posaconazole drug costs per observed isavuconazole days of therapy (DOT) during the study period. RESULTS: One hundred thirty-eight courses of isavuconazole prophylaxis were administered to 98 inpatients (2193 DOT). Relapsed/refractory acute myelogenous leukaemia was the indication for prophylaxis in over half (59.4%) of patients. Breakthrough IFI occurred in 8 (5.8%) courses. Suspected drug-related toxicities led to early discontinuation in 6 (4.3%) courses (five hepatotoxicity, one drug rash). At discharge, 24 (17.4%) courses lacked insurance coverage for isavuconazole. The formulary switch to isavuconazole prophylaxis resulted in an estimated mean drug cost savings of $128.25 per DOT relative to estimated posaconazole costs (P < 0.001). CONCLUSION: Isavuconazole may be an option for antifungal prophylaxis in high-risk immunocompromised adults and has the potential to produce significant inpatient drug cost savings. Further studies are needed to confirm the clinical efficacy and cost-effectiveness of isavuconazole in this role.

Cost-effectiveness analysis of isavuconazole versus voriconazole for the treatment of patients with possible invasive aspergillosis in Sweden.

BACKGROUND: Voriconazole is well established as standard treatment for invasive aspergillosis (IA). In 2017, isavuconazole, a new antifungal from the azole class, with a broader pathogen spectrum, was introduced in Sweden. A model has therefore been developed to compare the cost-effectiveness of isavuconazole and voriconazole in the treatment of possible IA in adults in Sweden. METHODS: The cost-effectiveness of isavuconazole versus voriconazole was evaluated using a decision-tree model. Patients with possible IA entered the model, with 6% assumed to actually have mucormycosis. It was also assumed that pathogen information would become available during the course of treatment for only 50% of patients, with differential diagnosis unavailable for the remainder. Patients who were considered unresponsive to first-line treatment were switched to second-line treatment with liposomal amphotericin-B. Data and clinical definitions included in the model were taken from the published randomised clinical trial comparing isavuconazole with voriconazole for the treatment of IA and other filamentous fungi (SECURE) and the single-arm, open-label trial and case-control analysis of isavuconazole for the treatment of mucormycosis (VITAL). A probabilistic sensitivity analysis was used to estimate the combined parameter uncertainty, and a deterministic sensitivity analysis and a scenario analysis were performed to test the robustness of the model assumptions. The model followed a Swedish healthcare payer perspective, therefore only considering direct medical costs. RESULTS: The base case analysis showed that isavuconazole resulted in an incremental cost-effectiveness ratio (ICER) of 174,890 Swedish krona (SEK) per additional quality adjusted life-year (QALY) gained. This was mainly due to the efficacy of isavuconazole against IA and mucormycosis, as opposed to voriconazole, which is only effective against IA. Sensitivity and scenario analyses of the data showed that the average ICER consistently fell below the willingness to pay (WTP) threshold of 1,000,000 SEK. The probability of isavuconazole being cost-effective at a WTP of 170,000 SEK per QALY gained was 50% and at a WTP of 500,000 SEK per QALY gained was 100%. CONCLUSIONS: This model suggests that the treatment of possible IA with isavuconazole is cost-effective compared with treatment with voriconazole from a Swedish healthcare payer perspective.

Impact of Non-Adherence and Flare Resolution on the Cost-Effectiveness of Treatments for Gout: Application of a Linked Pharmacometric/Pharmacoeconomic Model.

BACKGROUND: Dual urate-lowering therapy (ULT) with lesinurad in combination with either allopurinol or febuxostat is an option for patients with gout unsuccessfully treated on either monotherapy. Treatment failure is often a result of poor medication adherence. Imperfect adherence in clinical trials may lead to biased estimates of treatment effect and confound the results of cost-effectiveness analyses. OBJECTIVES: To estimate the impact of varying medication adherence on the cost effectiveness of lesinurad dual therapy and estimate the value-based price of lesinurad at which the incremental cost-effectiveness ratio is equal to £20,000 per quality-adjusted life-year (QALY). METHODS: Treatment effect was simulated using published pharmacokinetic-pharmacodynamic models and scenarios representing adherence in clinical trials, routine practice, and perfect use. The subsequent cost and health impacts, over the lifetime of a patient cohort, were estimated using a bespoke pharmacoeconomic model. RESULTS: The base-case incremental cost-effectiveness ratios comparing lesinurad dual ULT with monotherapy ranged from £39,184 to £78,350/QALY gained using allopurinol and £31,901 to £124,212/QALY gained using febuxostat, depending on the assumed medication adherence. Results assuming perfect medication adherence imply a per-quarter value-based price of lesinurad of £45.14 when used in dual ULT compared with allopurinol alone and £57.75 compared with febuxostat alone, falling to £25.41 and £3.49, respectively, in simulations of worsening medication adherence. CONCLUSIONS: The estimated value-based prices of lesinurad only exceeded that which has been proposed in the United Kingdom when assuming both perfect drug adherence and the eradication of gout flares in sustained treatment responders.

Nitric Oxide Releasing Nanoparticles as a Strategy to Improve Current Onychomycosis Treatments.

Topical antimicrobials are the ideal mode of onychomycosis treatment for efficient drug delivery and avoidance of sytemic effects associated with oral medications. However, high treatment costs, tissue penetration limitations, and low cure rates have continued to pose major challenges. To capitalize on the progress made by topical efinaconazole solution, efinaconazole was combined with inexpensive, previously-characterized nitric oxide releasing nanoparticles (NO-np), which have been shown to offer sustained nitric oxide release over time and enhanced barrier penetration, while exerting broad spectrum antimicrobial and immunomodulating properties. NO-np were combined with efinaconazole in varying concentrations and applied against reference strains of Trichophyton rubrum using a checkerboard method. Results demonstrated synergism of NO-np+efinaconazole against T. rubrum, which is noteworthy given the barriers present in the topical treatment of onychomycosis, and the multiple potential benefits offered by NO-np. Overall, this study illustrates the untapped potential of nanotechnology in the treatment of disorders of the skin, hair, and nails where drug delivery remains a challenge. J Drugs Dermatol. 2018;17(7):717-720.

Economic impact of treating invasive mold disease with isavuconazole compared with liposomal amphotericin B in the UK.

AIM: Invasive mold diseases (IMDs) are associated with significant morbidity and mortality. Approved treatments include voriconazole (VORI), liposomal amphotericin B (L-AMB), posaconazole (POSA) and isavuconazole (ISAV). A UK-based economic model was developed to explore the cost of treating IMDs with ISAV versus L-AMB followed by POSA. MATERIALS & METHODS: As indirect comparisons have demonstrated similar efficacy between the comparators, a cost-minimization approach was taken. Drug acquisition, administration & monitoring, and hospitalization costs were evaluated from the healthcare system perspective. RESULTS: Per-patient costs were UK£14,842 with ISAV versus UK£18,612 with L-AMB followed by POSA. Savings were driven by drug acquisition, and administration & monitoring costs. CONCLUSION: ISAV has the potential to reduce IMD treatment costs relative to L-AMB followed by POSA.

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 Ribociclib plus Letrozole Versus Palbociclib plus Letrozole and Letrozole Monotherapy in the First-Line Treatment of Postmenopausal Women with HR+/HER2- Advanced or Metastatic Breast Cancer: A U.S. Payer Perspective.

BACKGROUND: U.S. regulatory approvals of the cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors ribociclib and palbociclib as add-ons to letrozole greatly enhance the prospects for treating postmenopausal women with hormone receptor-positive (HR+)/human epidermal receptor 2-negative (HER2-) advanced or metastatic breast cancer. Clinical trials have established that the combination of a CDK 4/6 inhibitor with letrozole can significantly improve progression-free survival (PFS) versus letrozole monotherapy and is safe and well tolerated. Cost-effectiveness studies are required to inform payers and clinical decision makers on the money value of combination treatment in clinical practice. OBJECTIVE: To evaluate the cost-effectiveness of ribociclib plus letrozole versus palbociclib plus letrozole and versus letrozole monotherapy in the first-line treatment of postmenopausal women with HR+/HER2- advanced or metastatic breast cancer from a U.S. private third-party payer perspective. METHODS: A partitioned survival model including 3 health states (progression free, with either overall response or stable disease; progressed disease; and death) simulated lifetime costs and outcomes over a 40-year lifetime horizon with a 1-month cycle length. Clinical efficacy data (PFS and overall survival [OS]) were derived from a phase III trial of ribociclib plus letrozole (MONALEESA-2; NCT01958021), a phase II trial of palbociclib plus letrozole (PALOMA-1; NCT00721409), and a Bayesian network meta-analysis. Health care costs included drug acquisition and monitoring, disease management, subsequent therapies, and serious drug-related adverse events. Effectiveness was measured in life-years, derived from survival projections, and in quality-adjusted life-years (QALYs), calculated from time spent in each state combined with health-state utility values. A one-way deterministic sensitivity analysis explored the impact of uncertainty in key model parameters on results, and probabilistic uncertainty was assessed through a Monte Carlo probabilistic sensitivity analysis. RESULTS: Ribociclib plus letrozole was dominant versus palbociclib plus letrozole, with a cost saving of $43,037 and a gain of 0.086 QALYs. Compared with letrozole monotherapy, ribociclib plus letrozole was associated with an incremental cost of $144,915 and an incremental QALY of 0.689, equating to an incremental cost-effectiveness ratio of $210,369 per QALY. Key model drivers included OS HRs for palbociclib plus letrozole versus letrozole and for ribociclib plus letrozole versus letrozole, the PFS HR for palbociclib plus letrozole versus letrozole, PD health-state costs, utility of response, and cost discount rate. The probabilities that ribociclib plus letrozole was cost-effective versus letrozole at thresholds of $50,000, $100,000 and $200,000 per QALY gained were 1.6%, 6.3%, and 50.5%, respectively. CONCLUSIONS: In the United States, ribociclib plus letrozole is a cost-effective alternative to palbociclib plus letrozole for the first-line treatment of postmenopausal women with HR+/HER2- advanced or metastatic breast cancer. Ribociclib plus letrozole is also cost-effective versus letrozole monotherapy at willingness-to-pay thresholds greater than $198,000 per QALY (for probabilistic analysis). DISCLOSURES: Funding for this study was provided by Novartis, which manufactures ribociclib and provided input on the study design and data collection, analysis, and interpretation. Mistry, May, Suri, and Young are employees of PAREXEL. Tang, Mishra, D. Bhattacharyya, and Dalal are employees of Novartis. S. Bhattacharyya was an employee of Novartis during the study period. Tang and Dalal hold stock in Novartis. Brixner, Oderda, and Biskupiak were paid by Millcreek Outcomes Group as consultants for work on this project. Brixner has also consulted for AstraZeneca, UCB, Regeneron, and Abbott.

Budget impact of adding lesinurad for second-line treatment of gout: a US health plan perspective.

Aim: To estimate budget impact of adopting lesinurad as add-on to allopurinol for urate-lowering therapy in gout. Methods: A budget impact model was developed for a US payer perspective, using a Markov model to estimate costs, survival and discontinuation in a one-million-member health plan. The population included patients failing first-line gout therapy, followed for 5 years. Results: Incremental costs of adding lesinurad versus no lesinurad were US$241,907 and US$1,098,220 in first and fifth years, respectively. Cumulative 5-year incremental cost was US$3,633,440. Estimated incremental mean cost per treated patient with gout per year was US$112. The mean per-member per-month cost increased by US$0.06. Conclusion: Initiating lesinurad would result in an incremental per-member per-month cost of US$0.06 over 5 years.

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 analysis of suvorexant for the treatment of Japanese elderly patients with chronic insomnia in a virtual cohort.

AIMS: This study assessed the cost-effectiveness of the orexin receptor antagonist suvorexant against zolpidem, the most widely used hypnotic benzodiazepine receptor agonist in Japan. To this end, a model was used that factored in insomnia and the risk for hip fractures, which have devastating effects on the elderly. METHODS: Data were derived from published papers. The target population was a virtual cohort of elderly patients (≥65 years) with insomnia residing in Japan. Cost-effectiveness was evaluated using quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio as effectiveness measures. The investigators assumed the perspective of healthcare payers. RESULTS: In the base-case analysis, suvorexant was cost-saving (suvorexant: $252.3, zolpidem: $328.7) and had higher QALYs gained (suvorexant: 0.0641, zolpidem: 0.0635) for elderly Japanese patients with insomnia compared with zolpidem, indicating that suvorexant was dominant. In the sensitivity analysis, the outcome changed from dominant to dominated due to the relative risk for hip fractures associated with suvorexant. However, when the other parameters were varied from the lower to the upper limits of their ranges, suvorexant remained dominant compared to zolpidem. LIMITATIONS: The relative risk for hip fractures for suvorexant used in the model was based on data from pre-approval clinical trials. More precise data may be needed. CONCLUSIONS: Suvorexant seemed to be more cost-effective than the alternative zolpidem. The findings suggested that suvorexant might be a viable alternative to zolpidem for elderly patients with insomnia. A sensitivity analysis showed that outcome varied depending on the relative risk for hip fractures associated with suvorexant. Further investigations may be needed for more precise results.

Cost-Effectiveness Analysis of Lesinurad/Allopurinol Versus Febuxostat for the Management of Gout/Hyperuricemia in Italy.

BACKGROUND: Until very recently the only therapeutic alternative for the management of patients affected by gout/hyperuricemia that did not respond to a first-line treatment based on allopurinol alone or who cannot tolerate allopurinol was febuxostat, a xanthine oxidase non-purine-selective inhibitor. Lately, however, a new therapeutic alternative has become available for the management of this pathology: lesinurad, a urate transporter inhibitor. OBJECTIVE: To objective of this study was to evaluate the cost effectiveness of lesinurad/allopurinol in comparison with febuxostat as a second-line therapeutic strategy for the management of patients affected by gout and hyperuricemia that did not respond to a first-line therapy based on allopurinol alone. METHODS: A Markov model was built based on the natural history of the pathology; patients entered the model according to their level of serum uric acid concentration and flowed across it according to their response to the therapy. The analysis was carried out considering the perspective of the Italian National Health Service on a lifetime horizon and 6-month cycles. Costs and quality-adjusted life-years (QALYs) were discounted at a 3.5% yearly rate. The results of the model were expressed in terms of incremental cost-effectiveness ratio (ICER). Both a one-way and a multi-way Monte-Carlo analysis were carried out in order to check the robustness of the results achieved. RESULTS: The ICER derived from the comparison was equal to €77.53/QALY on the lifetime horizon, as there was a higher level of costs associated with the combination as compared with febuxostat (€10,658.27 vs. €10,645.87, for a differential of €12.40) and a higher level of QALYs achieved (7.77 vs. 7.61, for a differential of 0.16). CONCLUSIONS: The lesinurad/allopurinol combination is recommended for the treatment of patients affected by gout/hyperuricemia in the Italian Health System as it appears to be cost effective and thus sustainable for the Italian healthcare sector.

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.