[Budget impact analysis of empagliflozin for the treatment of type 2 diabetes in Italy]

BACKGROUND: Empagliflozin is the most recent molecule in the SGLT-2i class, new antidiabetic drugs that reduce renal glucose absorption by determining the excretion in the urine. The high prevalence of T2D, the chronicity of the condition and the severe economic and social burden caused by the disease, impose the need for a careful health economic assessment on each therapeutic innovation in this area.AIM: The aim of this study was to assess the budget impact of adopting empagliflozin in the diabetic population currently treated with sulfonylureas and potentially eligible for treatment with SGLT-2i.METHODS: The budget impact analysis was conducted from the perspective of the Italian National Health Service over a period of three years, through an analytic model developed in MS Excel. The target population was estimated in about 170,000 patients currently treated with sulfonylureas, based on the growth forecasts of the Italian population, epidemiological estimates and drug-use information available in the literature on diabetes in Italy. In the base case was assumed a replacement rate of sulfonylureas equal to 10%, 20% and 30% respectively at the first, second and third year of analysis. A scenario analysis was considered assuming a constant uptake of 100% since the first year. The following direct healthcare costs were considered: 1) acquisition of antidiabetic drugs as the main therapy and as rescue therapy; 2) self-monitoring of blood glucose; 3) management of severe hypoglycemic events and 4) management of major cardiovascular events. Clinical effectiveness data was based on the published literature and unit costs were derived from current prices and tariffs. Oneway sensitivity analysis was developed to assess the impact of input's uncertainty on the overall result.RESULTS: The base case analysis presented a substantially neutral impact on the budget. The 3-year cumulative impact was -454.337 €, corresponding to a 0.1% saving. This means that the replacement of sulphonylureas with empagliflozin determines an increase in acquisition costs of drugs, which is entirely offset by the reduction in costs of self-monitoring of blood glucose, management of hypoglycemic events and cardiovascular events. The scenario analysis, based on the assumption of a full substitution of sulphonylureas with empagliflozin at the first year, yielded a more enhanced savings. The cumulative impact was -2.269.517 €, corresponding to a 0.6% saving.CONCLUSIONS: The present study shows that the replacement of sulfonylureas (a class of generic products) with empagliflozin, motivated by the advantageous efficacy and safety profile, can take place optimizing healthcare expenditure for the management of DT2.[In Italian

Cost-effectiveness of ponatinib in chronic myeloid leukemia in Italy:

An area-under-the-curve Markov model was designed to evaluate the cost-effectiveness of ponatinib as a third line treatment of Chronic Myeloid Leukemia-Chronic Phase (CML-CP) with reference to Italy. As for current guidelines, comparators were dasatinib, nilotinib, bosutinib, allogeneic stem cell transplantation (SCT), hydroxyurea. The economic perspective was the Italian National Health Service's (NHS), where costs for treatment drugs, monitoring and follow-up, adverse events, SCT procedure were considered on a lifetime span. Costs (mainly based on current tariffs in Italy) and benefits (QALYs) were discounted at a 3.5% annual rate. Ponatinib resulted dominant versus SCT. The lowest ICER was €13,090 (ponatinib vs hydroxyurea); the highest was €22,529 (ponatinib vs dasatinib). Sensitivity analysis – both deterministic (one way) and probabilistic – was focused on the comparison between ponatinib and dasatinib. The deterministic analysis showed that the most critical parameter in the model was ponatinib pri..

Valutazione farmacoeconomica della prevenzione con picotamide vs acido acetilsalicilico dei pazienti diabetici con vasculopatia periferica

Type 2 diabetes mellitus (DM) and peripheral arterial disease (PAD) are two very relevant cardiovascular (CV) risk factors, which can often be found concurrently in the same patient. The DAVID trial, a double-blind, randomized, aspirin(ASA)-controlled study, has demonstrated that the use of picotamide, a thromboxane A2 synthase and receptor dual inhibitor, is associated with lesser CV morbidity and mortality in this type of patients in comparison to ASA, considered the standard antiplatelet agent. In order to estimate clinical and economic impacts of picotamide in the Italian health care setting, we developed a pharmacoeconomic model based on clinical data from DAVID and national economic parameters and demographics. The base case scenario, which reflects current prices and reimbursement policy (i.e. ASA fully paid for, picotamide out-of-pocket for patients) yielded an incremental cost/effectiveness ratio (ICER) of about 8,500 euro/year of life (YOL) saved, which falls below conventionally adopted willingness to pay thresholds. This cost, however, is totally born by the patient, while the savings on health care expenditures for avoided events (and less ASA) benefit the national health service (NHS). These results may help the physician in explaining the consequences of this choice to his/her patients, facilitating a fully-informed choice. The availability of a theoretical model allowed to explore some alternative scenarios, that indicate that the ICER can be further lowered and the economical burden better distributed through policy changes. In conclusion, the pharmacoeconomic model indicated that picotamide is likely to be a cost/effective option for CV mortality and morbidity prevention in patients with concurrent type 2 DM and PAD and that the level of adoption of this strategy will depend on willingness to pay and policy priorities of the NHS and patients themselves

Sviluppo e implementazione di un modello farmacoeconomico per valutare la costo efficacia di un ACE-inibitore nella prevenzione del rischio cardiovascolare

Cardiovascular disease (CVD) remains one of the leading causes of mortality and morbidity worldwide. Since several pharmacological approaches are available for the reduction of incidence and severity of cardiovascular events and health resources in modern managed care systems are limited, the evaluation of the clinical and economical consequences of any treatment is very valuable for decison-makers and physicians. In this article we present a flexible pharmacoeconomic model that permits the calculation of the marginal costeffectiveness of cardiovascular prevention with ramipril, a drug of the class of ACE-inhibitors. The clinical data used for the modelization are derived from the HOPE (Heart Outcomes Prevention Evaluation) study, a landmark cardiovascular prevention study that showed how the benefits of ACE-inhibition with ramipril go beyond the effects on blood pressure, while Italian epidemiological, demographic and economical data make the results appliable to the Italian population. The model, structured as a decision tree comparing the alternatives "to treat" or "not to treat" with Markow chains at the terminal nodes, calculates the marginal cost-effectiveness of the preventive treatment in terms of cost/year of live saved. The model is characterized by high flexibility, as it allows health decision-makers to set epidemiological and economical data in order to reflect the local population at high risk for developing cardiovascular diseas. The model was tested on a high risk population, formed by all acute myocardial infarction survivors in Italy, and indicated that life-long treatment of this patients would yield significant clinical benefits, with a cost/ effectiveness of 3,932 euro/year of life saved. This value is well below the standards that are considered acceptable, and offsprings from the partial offset of pharmaceutical costs caused by the reduction in the expenses for diagnosis and treatment of the cardiovascular events avoided with the preventive therapy

An Integrated Management Model of Patients With Atrial Fibrillation: The Experience of the Local Health Unit Tuscany North-West

Atrial fibrillation (AF) is the most prevalent form of alteration in cardiac rhythm and is associated with a high economic burden resulting from both clinical consequences and impact on patients’ quality of life. Goals of treatment include symptom control and, in the high-risk patients, the prevention of thromboembolic complications. The advent of novel oral anticoagulant agents (NOACs) has improved the management of patients with non-valvular AF (NVAF) by overcoming limitations associated with traditional oral anticoagulation drugs. NOACs are associated with a lower risk of stroke, systemic embolism, and mortality compared to vitamin K antagonists (VKAs) and with a lower risk of fatal, major, and intracranial bleeding. This supplement aims at sharing the virtuous management model of AF patients in the Local Health Unit Tuscany North-West and promoting the importance of a multidisciplinary management, which involves cardiologists and general practitioners (GPs), not only in terms of clinical outcomes, but also of therapeutic appropriateness and economic sustainability

Cost-effectiveness analysis of empagliflozin in the treatment of patients with type 2 diabetes and established cardiovascular disease in Italy, based on the results of the EMPA-REG OUTCOME study

INTRODUCTION: The EMPA-REG OUTCOME trial demonstrated the efficacy of empagliflozin in the treatment of type 2 diabetes (T2D) with a previous history of cardiovascular (CV) disease. The drug is currently reimbursed for T2D Italian patients, but the reduction of CV mortality and morbidity shown in the trial opens a new treatment perspective in those patients with associated high CV risk.OBJECTIVE: Cost-effectiveness analysis of empagliflozin for the treatment of T2D patients with a previous history of CV disease, from the Italian National Health Service (NHS) perspective.METHODS: The analysis was performed with an individual simulation model, which can predict the time to CV events or death through a set of time-dependent regressions estimated on the patient-level data of the EMPA-REG OUTCOME trial. This design allows the direct simulation of long-term outcomes and costs without the need for surrogate endpoints.The model was adapted to the Italian setting, considering local epidemiological data, baseline quality of life (QoL) utility, background mortality and unit costs from current prices and tariffs. The cost perspective was that of the Italian NHS and the horizon of the simulation was lifetime. Costs and benefits were discounted at a 3.5% rate.RESULTS: Base case results were estimated on a cohort of 5,000 patients, which ensured the convergence of the simulation. Patients treated with empagliflozin in add-on to the standard of care (SoC) lived on the average 13.8 undiscounted years as compared to 11.8 years of patients on SoC alone. The gain in discounted quality-adjusted life years (QALYs) was 1.0, due to improved survival and QoL linked to the reduced incidence of CV events and CV mortality. The incremental cost-effectiveness ratio (ICER) was 4,811 €/QALY, well below the commonly applied threshold of 30,000-50,000 €/QALY.CONCLUSION: Empagliflozin in add-on to the SoC is a highly cost-effective strategy for the treatment of T2D patients with known CV disease in the Italian setting

[Budget impact analysis for peginterferon beta-1a in relapsing remitting multiple sclerosis in Italy]

 BACKGROUND: Peginterferon beta-1a, injected every two weeks, is the first approved pegylated interferon beta-1a for the treatment of relapsing remitting multiple sclerosis (RRMS). The objective of this analysis was to estimate the economic impact due to the introduction of peginterferon beta-1a in Italy.METHODS: This analysis was conducted with a three-year time horizon with the support of a simple decision-analytic model adopting the perspective of the Italian National Healthcare Service (NHS). Healthcare costs sustained by the Italian NHS to manage the RRMS population (drug treatment, monitoring, relapse management, adverse events management) were calculated over 3 years and compared in two scenarios: the base scenario where interferons-beta and glatiramer acetate (GA) are used to treat RRMS patients, and an alternative scenario where peginterferon beta-1a can also be used to treat RRMS patients. The target population was approximately 35,500, 37,500 and 39,500 patients at year 1, 2 and 3 respectively, based on the published literature and market data. The efficacy of treatments was simulated as a reduction of relapse rates and was derived from a Network Meta-analysis. Unit costs were based on current prices and tariffs, and the published literature. A one-way sensitivity analysis was developed.RESULTS: According to current price and described assumptions, it was estimated that the introduction of peginterferon beta-1a would result in a decrease of total costs when compared with the base scenario. The cost in the base scenario was estimated to be  € 321.5, € 339.7 and € 357.8 million in years 1, 2, and 3, respectively. In the alternative scenario, the same costs resulted in about € 321.1, € 338.6 and € 356.2 million, respectively. The cumulative budget impact over three years period was approximately a cost saving of € 3.1 million (about 0.3% saving).CONCLUSION: The adoption of peginterferon beta-1a for the treatment of RRMS would be viewed as economically sustainable by the Italian NHS.[Article in Italian

Analisi di costo efficacia nella terapia della BPCO

Current practice guidelines for the treatment of COPD recommend the use of combined inhaled corticosteroids and long-acting bronchodilators in severe and very severe patients (GOLD stages III and IV). OBJECTIVES: To analyze the economical and clinical impact of this recommendation, the affordability of its widespread application, as well as the relative pharmacoeconomical performance of the available options for severe and very severe COPD in Italy. METHODS: Published data on the Italian COPD population were fitted in a disease progression model based on a Markov chain representing severity stages and death. Alternative therapeutic options (salmeterol/ fluticasone - SF, formoterol/budesonide - FB, salmeterol alone - S, fluticasone alone - F and control - C) were represented as competing arms in a decision tree. Efficacy data from international trials were expressed in terms of risk reduction. Clinical parameters used were number of exacerbations and symptom-free days. Direct and indirect costs were considered and valued according to present prices and tarifs. The analyses were conducted from National Health System, societal and patient perspectives with time horizons of 1,5, and 10 years, and lifelong. RESULTS: The yearly total direct costs of treating COPD patients in Italy is estimated in approximately 7 billion Euro, with a mean cost/patient/year around 2,400 Euro. Mean survival of the cohort is 11,5 years. The C and F strategies are dominated (i.e. are associated with worse outcomes and higher costs) by all alternatives. S/F and F/B are the most effective strategies, with a slight clinical superiority of the latter, but are also marginally more expensive than S. Incremental cost/effectiveness of S/F vs. S is 679,55 Euro/avoided exacerbation and 3,31Euro/gained symptom-free day. CONCLUSIONS: The recommended use of combined inhaled corticosteroids and long-acting bronchodilators for severe and very severe COPD patients, as compared with current practice, has the potential of improving clinical outcomes without increasing health care costs

[Budget impact analysis of idarucizumab for the management of patients treated with dabigatran in emergency / urgent situations in Italy]

BACKGROUND: Each drug therapy with an anticoagulant effect may require, in emergency conditions, a rapid and specific strategy for a prompt restoration of coagulation. Dabigatran is the first-in-class of the so-called new oral anticoagulants (NAO), that have been made available in recent years in addition to traditionally-used vitamin K antagonists (VKA). Idarucizumab is a monoclonal antibody that binds to dabigatran, neutralizing its anticoagulant effect.OBJECTIVE: To assess the economic effect of idarucizumab in patients treated with dabigatran when the rapid reversal of its anticoagulant effect is required.METHODS: The analysis was carried over through the development of a budget impact model specifically adapted to the context of Italian care. The analysis was conducted along a time horizon of five years. The target population was defined by those patients on dabigatran treatment presenting uncontrolled and life-threatening bleedings (gastro-intestinal, intracranial or other) or requiring emergency surgery or urgent procedures. The estimation of healthcare resources (i.e. diagnostic procedures, medications, and other in-hospital services) needed for the management of uncontrolled bleeding and emergency surgery in patients treated with dabigatran was obtained from a panel of five Italian Clinical Experts. Unit costs were derived from current prices and tariffs.RESULTS: The total cost of management with the current therapeutic modalities ranged from € 16.5 million in year 1 to € 20.1 million in year 5. In the scenario with idarucizumab the total cost ranged from € 15.4 million in year 1 to € 18.7 million in year 5. The adoption of idarucizumab resulted in a cumulative 5-year savings of 6.5 million euro corresponding to 7.1% of the total expense.CONCLUSION: Idarucizumab for the management of patients treated with dabigatran in emergency / urgent situations has the potential for substantial savings, compared to treatments currently available. This preliminary assessment will require further confirmatory evidence when the product will become available in Italian healthcare setting.[Article in Italian