Extemporaneous combination therapy with nebivolol/ramipril for the treatment of hypertension: a real-world evidence study in Europe.

OBJECTIVES: To describe the clinical characteristics and treatment adherence in European adult hypertensive patients starting treatment with the extemporaneous combination of nebivolol and ramipril (NR-EXC). METHODS: Retrospective database analysis of patients receiving NR-EXC treatment across five European countries (Italy, Germany, France, Poland, Hungary) over a period ranging from 3 to 9 years (until 30 June 2020) according to data availability for the different data sources. Patient demographics, comorbidities, and treatment adherence were evaluated. RESULTS: We identified 592,472 patients starting NR-EXC. Most of them were over 60 years of age, with ramipril most commonly prescribed at 5 mg (from 30.0 to 57.2% of patients across the databases). Notable comorbidities included diabetes (19.2%) and dyslipidemia (18.2%). The study population was also highly subjected to polytherapy with antithrombotics, lipid-lowering agents, and other lowering blood pressure agents as the most co-prescribed medications, as resulted from Italian database. Up to 59% of the patients did not request a cardiologic visit during the study period. Adherence to therapy was low in 56.3% of the patients, and it was high only in 11.1% of them. CONCLUSIONS: The combination of nebivolol and ramipril is frequently prescribed in Europe, but adherence to treatment is suboptimal. The transition to a single pill combination could enhance treatment adherence and streamline regimens, potentially leading to significant benefits. Improved adherence not only correlates with better blood pressure control but also reduces the risk of cardiovascular events, underscoring the importance of this development.

Extemporaneous combination therapy with nebivolol/valsartan for the treatment of hypertension: a study of real-world evidence in Europe.

OBJECTIVE: To explore real-life use of the extemporaneous combination of nebivolol and valsartan (NV-EXC) in adult hypertensive patients in Europe. METHODS: Retrospective analysis of patients starting NV-EXC treatment conducted using prescription databases in Italy, Germany, Hungary, and Poland. The selection period during which study patients were identified covered a time span ranging from 3 to 9 years (until 30 June 2020) according to availability of the different data sources. Patient demographics, clinical information, and treatment adherence, measured by proportion of days covered, were evaluated. Additionally, the potential eligibility of Italian patients for the single pill combination (SPC) of nebivolol and valsartan over a one-year period was estimated. RESULTS: The study included 170,682 patients initiating NV-EXC across the databases. Most patients were females (from 51 to 60%) and primarily aged over 60 years. Few patients received prescriptions of both available dosages of valsartan (80 and 160 mg) during follow-up (from 3.2 to 8.5%). Common comorbidities included dyslipidemia (19.2%) and diabetes (19.1%). Around 59.5% of patients did not require cardiologic visits during the study period. Adherence to NV-EXC, as indicated by the Italian database, was low in 53.3% of patients, with only 16.1% showing high adherence. The Italian database revealed 680 prevalent NV-EXC users in 2019, estimating a potential 30,222 adult patients eligible for the nebivolol/valsartan SPC. CONCLUSIONS: The combination of nebivolol and valsartan is frequently prescribed for hypertension, but adherence remains a challenge. A potential nebivolol/valsartan SPC holds promise in enhancing adherence and optimizing therapeutic outcomes for hypertension management.

Extemporaneous combination therapy with nebivolol/amlodipine for the treatment of hypertension: a real-world evidence study in Europe.

OBJECTIVE: The investigation of the real-world use of the extemporaneous combination of nebivolol and amlodipine (NA-EXC) in adult patients diagnosed with hypertension in Europe. METHODS: Retrospective analysis of data extracted from seven databases of patient medical records and prescriptions from Italy, Germany, France, Hungary, and Poland, to determine the prevalence and incidence of NA-EXC use and to estimate the number of patients potentially eligible for a single-pill combination of the two antihypertensives. Secondary objectives included: the description of the population of NA-EXC users and the assessment of their adherence to treatment based on the proportion of days covered. RESULTS: The use of NA-EXC was found to be common in Europe and ranged between 2.9% to 9.9% of all patients identified in the databases with a prescription of nebivolol and/or amlodipine. The estimated numbers of patients potentially eligible in 2019 for a single-pill combination of nebivolol and amlodipine in Italy and Germany were, respectively, 178,133 and 113,240. Users of NA-EXC were mostly aged 70-79 years, had metabolic disorders and other comorbidities; >70% of them had received ≥2 concomitant medications before starting NA-EXC. Adherence to NA-EXC was defined as high only in 15.6% to 35% of patients. CONCLUSIONS: The extemporaneous combination of nebivolol and amlodipine is commonly prescribed in Europe, however adherence to the therapy is poor. The development of a single-pill combination of nebivolol and amlodipine may improve adherence by reducing the number of pills administered to patients and thus simplifying treatment regimens.

Efficacy and safety of biosimilar Peg-filgrastim after autologous stem cell transplant in myeloma and lymphoma patients: a comparative study with biosimilar Filgrastim, Lenograstim, and originator Peg-filgrastim.

Data about biosimilar Peg-filgrastim (bioPEG) in autologous stem cell transplant (ASCT) are still scarce. The aim of this study has been to assess efficacy and safety of bioPEG among lymphoma and myeloma patients undergoing ASCT, comparing these data with historical controls receiving other G-CSFs. Furthermore, an economic evaluation has been included to estimate the savings by using bioPEG. This is a prospective cohort study comparing lymphoma and myeloma patients undergoing ASCT and receiving bioPEG (n = 73) with three historical consecutive cohorts collected retrospectively who received other G-CSFs (Lenograstim - Leno - n = 101, biosimilar Filgrastim - bioFIL n = 392, and originator Peg-filgrastim - oriPEG n = 60). We observed a significantly shorter time to neutrophils and platelet engraftment (p < 0.001) in patients treated with bioPEG and oriPEG. Moreover, patients who received bioPEG showed a shorter hospitalization time (p < 0.001) and a lower transfusion need (p < 0.001). We did not observe any significant difference in terms of transplant-related mortality, mucositis, and diarrhea among the four groups. No serious adverse events were associated with bioPEG. Similar data were obtained after running a stratified analysis for lymphomas and myeloma separately conducted by using a propensity score matching. The average total cost per patient of bioPEG was € 18218.9 compared to € 23707.8, € 20677.3 and € 19754.9 of Leno, oriPEG, and bioFIL, respectively. In conclusion, bioPEG seems to be as effective as the originator and more effective than short-acting G-CSFs in terms of post-transplant engraftment in myeloma and lymphoma patients undergoing ASCT. Moreover, bioPEG was cost-effective when compared with the other G-CSFs.

Epidemiology of primary biliary cholangitis in Italy: Evidence from a real-world database.

BACKGROUND: Primary biliary cholangitis is an autoimmune disease affecting the interlobular bile ducts. Limited information is available on its epidemiology and treatment in Italy. AIMS: To describe primary biliary cholangitis epidemiology and investigate treatment patterns for Italian patients with this disease. METHODS: Electronic medical records from 900 general practitioners (part of the QuintilesIMS™ Longitudinal Patient Databases) were examined. Demographics were compared with those from the Italian National Institute of Statistics dataset. The International Classification of Diseases, Ninth Revision, biliary cirrhosis code 571.6 was used for diagnosis, and data on comorbidities, concomitant medications, medical examinations, specialist referrals, and treatments were collected. RESULTS: This dataset was representative of the Italian population. Point prevalence of primary biliary cholangitis was calculated as 27.90 per 100,000 and incidence as 5.31 per 100,000 inhabitants/year. Some associations between the disease and comorbidities were sex specific. The most common laboratory assays requested were for liver enzymes, and the majority of patients were not referred to a specialist. Ursodeoxycholic acid was the most common therapy. CONCLUSION: This can be used as a benchmark for monitoring and identifying unmet needs to improve treatment in Italy.

A cost-effectiveness modeling evaluation comparing a biosimilar follitropin alfa preparation with its reference product for live birth outcome in Germany, Italy and Spain.

BACKGROUND/OBJECTIVE: Although biosimilar drugs may be cheaper to purchase than reference biological products, they may not be the most cost-effective treatment to achieve a desired outcome. The analysis reported here compared the overall costs to achieve live birth using the reference follitropin alfa (GONAL-f) or a biosimilar (Ovaleap) in Spain, Italy and Germany. METHODS: Patient and treatment data was obtained from published sources; assisted-reproductive technology, gonadotropin, follow-up and adverse-event-related costs were calculated from tariffs and reimbursement frameworks for each country. Incremental cost-effectiveness ratios (ICERs) were calculated from the difference in costs between reference and biosimilar in each country, divided by the difference in live-birth rates. Mean cost per live birth was calculated as total costs divided by the live-birth rate. RESULTS: The published live birth rates were 32.2% (reference) and 26.8% (biosimilar). Drug costs per patient were higher for the reference recombinant human follicle-stimulating hormone in all three countries, with larger cost differences in Germany (€157.38) and Italy (€141.50) than in Spain (€22.41). The ICER for the reference product compared with the biosimilar was €2917.47 in Germany, €415.43 in Spain and €2623.09 in Italy. However, the overall cost per live birth was higher for the biosimilar in all three countries (Germany €8135.04 vs. €9185.34; Italy €8545.22 vs. €9733.37; Spain €14,859.53 vs. €17,767.19). Uncertainty in efficacy, mean gonadotropin dose and costs did not have a strong effect on the ICERs. CONCLUSIONS: When considering live birth outcomes, treatment with the reference follitropin alfa was more cost effective than treatment with the biosimilar follitropin alfa.

Non-persistence risk and health care resource utilization of Italian patients with non-valvular atrial fibrillation

The aim of this study is to compare discontinuation risk and health care resource utilization between vitamin K antagonists (VKAs) and non-vitamin K antagonist oral anticoagulants (NOACs) in newly treated patients with non-valvular atrial fibrillation (NVAF). Based on administrative databases of five Italian Local Healthcare Units, all patients with a discharge diagnosis of NVAF between 2011 and 2014 were selected. Among them, the incident users of NOACs and VKAs in 2014 were followed-up to from the first prescription date to the occurrence of anyone of the following events: a 90-day gap in therapy, switch to a different molecule or add-on of a different molecule into the regimen, death of patient, end of follow-up (December 2015). All-cause hospitalizations, outpatient visits and examinations within the persistence period were also evaluated. The final cohort was composed of 2909 and 765 incident users of VKA and NOACs, respectively. Cox regression to model time to non-persistence within 12 months showed a 62% reduction in risk of drug discontinuation in NOAC patients compared to VKA patients (HR,0.38 [0.33-0.44]). In the adjusted analyses with warfarin as reference, apixaban patients (HR, 0.35 [0.24-0.50]) had the lowest risk of non-persistence, followed by rivaroxoban (HR, 0.42 [0.33-0.54]) and dabigatran users (HR, 0.51 [0.43-0.61]). The mean total numbers of all-cause hospitalization records in 12-month persistent patients were significantly less in NOACs users compared with VKA users (0.36 vs 0.47, p-value:0.03). Similarly, the differences in the mean numbers of all-cause visits and examinations were statistically significant between VKA and NOAC patients, who registered on average 2.33 vs 1.84 visits (p-value: 0.01) and 24.4 vs 9.2 exams referrals (p-value: <0.0001), respectively. NOACs showed a better profile in terms of both resource utilization and persistence compared with VKAs. In particular, apixaban returned the lowest risk of discontinuation than dabigatran and rivaroxaban.

Severe intestinal malabsorption associated with ACE inhibitor or angiotensin receptor blocker treatment. An observational cohort study in Germany and Italy.

PURPOSE: The angiotensin II receptor blocker (ARB) olmesartan has been recently associated with sprue-like enteropathy (SLE), a gastrointestinal condition characterized by intestinal malabsorption (IM) and severe diarrhea. Whether the increased risk of SLE is substance-specific or a class effect involving all ARBs is uncertain. The aim of this study is to assess the risk of enteropathy associated with ARBs and angiotensin converting enzyme inhibitors (ACE-i) by using data from large administrative and claim databases. METHODS: We obtained data from Italian local health-care units and a large German claim database and included patients treated with olmesartan, other ARBs, and ACE-i. In the absence of a specific diagnosis code for SLE, International Classification of Diseases codes for IM were used. Analysis implemented a Poisson regression with robust error variance procedure, which allowed accounting for different clusters (local health-care units and countries) and correctly estimating the standard error for the relative risk of rare event occurrence. RESULTS: Patients were divided into 3 groups: olmesartan (25.591, 5.5%), other ARBs (104.901, 22.5%), and ACE-i patients (334.951, 72.0%). Baseline characteristics were similar overall. The incidence of unspecified IM in ACE-i patients was not different compared with that of olmesartan, whereas a higher rate ratio was observed when comparing ARB patients with the olmesartan group (RR: 2.50, 95% CI 1.21 to 5.19, P .01). When International Classification of Diseases codes for coeliac disease were included, no differences were observed. CONCLUSIONS: We could not confirm previous findings of a higher risk of malabsorption in olmesartan-only patients, and drug-induced enteropathy should be considered the result of exposure to the class of ARBs rather than a specific drug-related effect.

Unspecified intestinal malabsorption in patients treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers: a retrospective analysis in primary care settings.

OBJECTIVE: To investigate the possible relationship between the use of Angiotensin II Receptor Blockers (ARBs) or Angiotensin-Converting-Enzyme Inhibitors (ACE-i) and unspecified intestinal malabsorption (IM) within the Italian and German real-life context. RESEARCH DESIGN AND METHODS: a retrospective cohort of patients with a new unspecified IM diagnosis during the period 1 January 2010-31 December 2013 was extracted from Italian IMS Health Longitudinal Patient Database and German IMS Disease Analyzer. Only patients with at least one prescription of ARB or ACE-i medication during the 6 months preceding the IM diagnosis were included and then followed up for 12 months to assess treatment exposure. RESULTS: After stratification by year and molecule, the proportion of patients experiencing an unspecified IM diagnosis on total patients receiving ARBs or ACE-i ranged from 0% to 0.14%, showing no relevant differences between molecules and no time trends. CONCLUSIONS: this study indicates that ACE-i or ARBs were rarely associated to an unspecified IM diagnosis. No relevant difference between each specific ACE-i and ARB was highlighted.

Characteristics of newly diagnosed COPD patients treated with triple inhaled therapy by general practitioners: a real world Italian study.

Factors predicting prescriptions of triple therapy were investigated in a large group of general practitioners in Italy. In the population treated by identified general practitioners, a cohort of newly diagnosed chronic obstructive pulmonary disease patients was extracted from IMS Health Longitudinal Database during the period 2010-2013. From the diagnosis, 1-year follow-up was evaluated. Thirty-two thousand forty-six newly diagnosed chronic obstructive pulmonary disease patients were evaluated (57.7% male, mean age 67 years). During 2 years prior to diagnosis less than 13% of patients were requested with a pulmonology evaluation and less than 5% with a spirometry; 65.1% cases were prescribed with a respiratory drug, which in 9.6% of cases was inhaled corticosteroid/long-acting ß2-agonist fixed-dose combination. Two thousand and twenty eight patients (6.3% of the newly diagnosed chronic obstructive pulmonary disease patients) were treated with triple therapy during the first year of follow-up, whose 858 (42.3%) starting immediately, and 762 (37.6%) following an initial treatment with inhaled corticosteroid/long-acting ß2-agonist fixed-dose combination. Being older, being requested with pulmonologist evaluation or spirometry, being prescribed with a inhaled corticosteroid/long-acting ß2-agonist fixed-dose combination at diagnosis resulted independent predictors of triple therapy use. CHRONIC LUNG DISEASE: ENSURING CORRECT PRESCRIPTIONS FOR EARLY-STAGE DISEASE: An improved education program for doctors promoting correct use of medication for chronic lung disease is needed in Italy. Current guidelines state that inhaled corticosteroids (ICSs) should be reserved for patients with severe chronic obstructive pulmonary disease (COPD), but it appears that doctors do not always follow this advice. Fabiano Di Marco, at San Paolo Hospital-Università degli Studi di Milano, and co-workers analyzed data from 32,046 COPD patients newly-diagnosed by family doctors in Italy between 2010 and 2013. When the researchers followed up on patients after 1 year, 2028 (6.3%) of newly-diagnosed patients were being treated with triple inhaled therapy incorporating ICSs-42% of these patients had started triple therapy immediately upon diagnosis. Being an older male and having been prescribed with a ICS/LABA FDC at diagnosis were strong predictors of triple therapy use within 1 year from the diagnosis.

A cost-effectiveness evaluation comparing originator follitropin alfa to the biosimilar for the treatment of infertility.

OBJECTIVES: To perform a cost-effectiveness evaluation comparing the originator follitropin alfa (Gonal-f®) to the biosimilar (Bemfola®) in the Italian and Spanish contexts, with an assessment of the German and UK backgrounds. METHODS: Starting from the study by Rettenbacher et al, a cost-effectiveness model was developed in the Italian and Spanish contexts. Clinical data on subjects, doses of gonadotropin, pregnancies, live-born children, and ovarian hyperstimulation syndrome were used to feed the model. Costs related to drugs, hospitalizations, specialist visits, and examinations were retrieved from Italian and Spanish tariffs. Gonadotropin acquisition costs for Germany and the UK were also taken into account to expand the economical assessment to the other countries. The evaluation was done based on the National Health Service perspective. Sensitivity analyses, both univariate and probabilistic, as long as scenario analyses, tested the robustness of the model. RESULTS: Originator follicle-stimulating hormone (FSH) costs were €3,663 and €6,387 in Italy and Spain, respectively, whereas biosimilar FSH costs were €3,483 and €6,342. The efficacy was found to be 0.52 for the originator and 0.47 for the biosimilar. The average cost per live birth was estimated to be €7,044 and €12,283 for the originator FSH and €7,411 and €13,494 for the biosimilar for Italy and Spain, respectively. Furthermore, the originator FSH generated an incremental cost-effectiveness ratio of €3,600 for Italy and €900 for Spain compared to the biosimilar. Sensitivity analyses confirmed the results of the base case model. CONCLUSION: This analysis indicated that the originator FSH is a cost-efficient treatment strategy for Italian and Spanish health services compared to the biosimilar and it would be worthwhile extending this evaluation to other countries.

Clinical Implications of Switching Lipid Lowering Treatment from Rosuvastatin to Other Agents in Primary Care.

INTRODUCTION: Switching from any statin to another non-equipotent lipid lowering treatment (LLT) may cause a low-density lipoprotein cholesterol increase and has been associated with a higher probability of negative cardiovascular outcomes. The aim of the study was to assess the impact of switching from rosuvastatin to any other LLT on clinical outcomes in primary care. METHODS: This was a retrospective analysis based on data from IMS Health Longitudinal Patient Database, which is a general practice database including information of more than 1.0 million patients representative of the Italian population by age, and medical conditions. Patients that started on rosuvastatin (10-40 mg/day) between January 2011 and December 2013 were considered. The date of the first prescription was defined as the index date (ID). The observation period lasted from the ID to September 2015 or until LLT discontinuation, or the occurrence of an acute myocardial infarction (AMI), or death. RESULTS: The primary end point of the study was the occurrence of an AMI during the observation period. The final study population included 10,368 patients. During the observation period, 2452 (23.6%) patients were switched from rosuvastatin to another LLT. The majority of patients (55.6%) were switched to atorvastatin, followed by simvastatin (24.9%), simvastatin/ezetimibe combination (10.0%) and other statins (9.5%). Female gender (HR, hazard ratio, 1.10, 95% CI, confidence interval, 1.02-1.19, p = 0.04) and the presence of chronic kidney disease (HR 1.47, 95% CI 1.16-1.86, p = 0.05) were associated with a higher probability of switch. During the observation period, 113 patients experienced an AMI (incidence of 6.7 AMI/1000 patient-years). Multivariate analysis with Cox proportional hazards method, including switching as a time-dependent covariate, demonstrated that changing from rosuvastatin to another LLT was an independent predictor of AMI (HR 2.2, 95% CI 1.4-3.5, p = 0.001). CONCLUSION: We conclude that switching from rosuvastatin to another non-equipotent LLT may impart an increased risk of AMI and should be avoided. FUNDING: AstraZeneca SpA.

An assessment of chemotherapy-induced nausea and vomiting direct costs in three EU countries.

BACKGROUND: chemotherapy-induced nausea and vomiting (CINV) has been commonly reported as one of the most distressing adverse effects among treated patients with cancer. Inadequately treated, CINV can lead to increased resource utilization and severely impair patients' daily functioning and quality of life. Direct costs include acquisition cost of antiemetic drugs and rescue medication, administration devices, add-on treatments, such as hydration, and additional patient care, that is, nursing and physician time, unscheduled office visits, emergency room admissions, and, in some cases, extended hospitalization or readmission. There are many reports on the cost-effectiveness of antiemetic drugs, but information on the total cost per patient associated with CINV is limited. The costs associated with severe CINV episodes are considered responsible for the most significant part of the expenditures. SCOPE: The aim of this study was to investigate the management of CINV episodes in three European health-care environments and to estimate direct costs associated with severe CINV episodes. METHODS: An online survey addressed to Italian, German, and French oncologists and oncology nurses was performed. The survey included 41 questions about the management and the resource utilization for patients experiencing any CINV episode during the 6-month period preceding the survey. Furthermore, the cost associated with severe CINV episode management was estimated by adopting the National Health Service's perspective. FINDINGS: A large proportion of patients receiving chemotherapy experienced a CINV episode (34.4% in Italy, 50.2% in France, and 40.4% in Germany); among those, 8.8% in Italy, 11.6% in France, and 19.2% in Germany experienced a severe CINV episode. Compared with Italy, Germany and France presented a greater hospitalization rate following an unplanned visit to the oncology ward or an emergency room access due to CINV. In Italy, the mean cost per patient with a severe CINV episode resulted in approximately €389, about half of the mean cost in France (€750) and a third of the mean cost in Germany (€1,017). CONCLUSIONS: Severe CINV episodes requiring hospitalization, day hospital, or hospitalization extension involve a significant cost for the National Health Services; additional studies should be conducted in order to evaluate potential ways to offset these expenses.

Cost-effectiveness of asenapine in the treatment of patients with bipolar I disorder with mixed episodes in an Italian context.

INTRODUCTION: Bipolar disorder is a chronic disease characterized by periods of mania or hypomania, depression, or a combination of both (mixed state). Because bipolar disorder is one of the leading causes of disability, it represents an important economic burden on society. Asenapine (ASE) is a new second-generation antipsychotic developed and approved for the treatment of manic or mixed episodes associated with bipolar disorder. The objective of the present study was to assess the cost-effectiveness of ASE compared to olanzapine (OLA) in the treatment of patients experiencing mixed episodes associated with bipolar I disorder in the context of the Italian National Health Service (NHS). METHODS: A pharmacoeconomic model was developed to simulate the management of Italian bipolar I patients with mixed episodes over a 5-year time horizon by combining clinical parameters with resource utilization. An expert panel of Italian psychiatrists and health economists was responsible for adapting a UK model to the Italian context. The primary outcome measure of the economic evaluation was the incremental cost effectiveness ratio, where effectiveness is measured in terms of quality adjusted life-years gained. Scenario analyses, sensitivity analyses, and a probabilistic sensitivity analysis were performed to test the robustness of the model. RESULTS: This pharmacoeconomic model showed that ASE resulted to be dominant over OLA; in fact, ASE was associated with lower direct costs (derived largely by the savings from hospitalizations avoided) and also generated a better quality of life. Results were robust to changes in key parameters; both scenario analyses and sensitivity analyses demonstrated model reliability. CONCLUSIONS: Results from this study suggest that the management of bipolar I patients with mixed episodes using ASE as alternative to OLA can lead to cost saving for the Italian NHS and improve patients quality of life.

Cost-effectiveness analysis on the use of rFSH + rLH for the treatment of anovulation in hypogonadotropic hypogonadal women.

BACKGROUND: Hypogonadotropic hypogonadal women are characterized by ovarian functionality deficiency, caused by low concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). To recover reproduction functionality, recommended therapies for ovarian induction involve injections of FSH and LH medications. OBJECTIVE: Since important differences exist between recombinant and urinary gonadotropin therapies in terms of efficacy and cost, the objective of this study was to develop a cost-effectiveness model to compare recombinant FSH (rFSH) + recombinant LH (rLH) and highly purified human menopausal gonadotropin (HP-HMG). METHODS: A Markov model was developed, considering three cycles of therapy; probability of pregnancy and miscarriage were considered, and the efficacy was evaluated in terms of pregnancy occurrence. The perspective of the model was that of the Italian Health Service, so only direct cost (drugs, specialist visits, patient examinations, and hospitalizations) were included. RESULTS: rFSH + rLH is associated with a higher total cost (€3,453.50) and higher efficacy (0.87) compared with HP-HMG (€2,719.70 and 0.50). rFSH + rLH generated an incremental cost effectiveness ratio equal to €2,007.30 compared to HP-HMG; the average cost per pregnancy is estimated to be €3,990.00 for recombinant strategy and €5,439.80 for urinary strategy. Results of probabilistic sensitivity analysis were consistent with the abovementioned findings. CONCLUSION: Despite the higher acquisition cost in comparison to HP-HMG, rFSH + rLH resulted in a higher pregnancy rate, which makes it the recommended choice when considering cost-effectiveness of LH in supporting FSH-induced follicular gonadotropins in hypogonadotropic hypogonadal women.

The risk of metabolic disorders in patients treated with asenapine or olanzapine: a study conducted on real-world data in Italy and Spain.

BACKGROUND: Atypical antipsychotics are the main treatment for a large number of psychiatric illnesses, with fewer extrapyramidal effects than conventional antipsychotics. However, it has been suggested that their use is associated with increased risk of dyslipidemia and type 2 diabetes mellitus. OBJECTIVE: The risk of metabolic adverse effects associated with asenapine was assessed in comparison with that associated with olanzapine using real-world data. METHODS: This study was a retrospective analysis based on data extracted from the Italian and Spanish Cegedim Strategic Data Longitudinal Patient-Data databases. Patients with asenapine or olanzapine prescriptions were retrieved from September 2010 to December 2012 using strict inclusion criteria to guarantee minimization of confounders. Patients with type 2 diabetes mellitus and dyslipidemia were identified by using ICD9 codes and by antidiabetic and dyslipidemic drug prescriptions. The presence or absence of the metabolic condition was compared before and after treatment, and between cohorts. RESULTS: The retrospective analysis showed a lower risk of developing type 2 diabetes with asenapine than with olanzapine (2.2 vs 3.5%, respectively; p value: 0.0002) and of developing dyslipidemia (2.8 vs 6.8%, respectively; p value: 0.0001). CONCLUSIONS: Asenapine is associated with a lower risk of metabolic adverse effects than olanzapine, demonstrating its improved safety profile.

C-QUALITY: cost and quality-of-life pharmacoeconomic analysis of antidepressants used in major depressive disorder in the regional Italian settings of Veneto and Sardinia.

BACKGROUND: Major depression is a commonly occurring, seriously impairing, and often recurrent mental disorder. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are the treatments most commonly used for major depressive disorder. The objective of this study was to assess the cost-effectiveness of SSRIs and SNRIs in the treatment of major depressive disorder in two Italian regional settings, ie, Veneto and Sardinia. METHODS: A decision analytic model was adapted from the Swedish Dental and Pharmaceutical Benefits Agency to reflect current clinical practice in the treatment of major depressive disorder in the most significant Italian regions. This adaptation was possible as a result of collaboration with an expert panel of Italian psychiatrists and health economists. The population comprised patients with a first diagnosis of major depressive disorder and initiating one SSRI or SNRI drug for the first time. The time frame used was 12 months. Efficacy and utility data for the model were retrieved from the literature and validated by the expert panel. Local data were used for resource utilization and for treatment costs based on the perspective of each regional health service. Scenario analyses and probabilistic sensitivity analyses were performed to test the robustness of the model. RESULTS: Base case analysis showed that escitalopram is associated with the largest health gain (in quality-adjusted life years) and a lower total cost at one year for Sardinia (except for sertraline, against which it was cost-effective) and for Veneto, and therefore dominates the other treatment strategies, given that more quality-adjusted life years are achieved at a lower total cost. Scenario analyses and probabilistic sensitivity analyses support the robustness of the model. CONCLUSION: The results indicate that escitalopram is the most cost-effective pharmacologic treatment strategy for both regional health services compared with all SSRIs and all SNRIs used in the first-line treatment of major depressive disorder.

C-QUALITY: cost and quality-of-life pharmacoeconomic analysis of antidepressants in major depressive disorder in Italy.

INTRODUCTION: Major depressive disorder (MDD) is a common and disabling condition across the world. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are the most commonly used antidepressants. The objective of this study was to assess the cost-effectiveness [€ per quality-adjusted life year (QALY)] of all SSRIs and all SNRIs for the treatment of MDD in Italy. METHODS: A decision analytic model was adapted from the Swedish Dental and Pharmaceutical Benefits agency model to reflect current clinical practice in the treatment of MDD in the largest Italian regions. This adaptation was possible thanks to the collaboration of an expert panel of Italian psychiatrists and health economists. The model evaluated patients with a first diagnosis of MDD and initiating an SSRI or an SNRI for the first time. The time horizon was 12 months. Efficacy and utility data for the model were retrieved from the literature and validated by the expert panel. Local data were considered for resource utilization and for treatment costs based on each regional health service perspective. Population-weighted regional data were used to define a national model. Scenario simulations, one-way sensitivity analyses, and Monte Carlo simulations were performed to test the robustness of the model. RESULTS: The base case analysis showed that escitalopram was associated with a lower total cost (€ 1,562) and a larger health gain (QALYs) at 1 year (0.732) per patient and dominated the other treatment strategies since more QALYs were achieved at a lower total cost. Sensitivity analyses support the robustness of the model. CONCLUSION: The results indicate that escitalopram is the most cost-effective pharmacological treatment strategy for the Italian health service compared with other SSRIs and all SNRIs used in the first-line treatment of MDD.

Cost-effectiveness evaluation of escitalopram in major depressive disorder in Italy.

BACKGROUND: Depression has a lifetime prevalence of 10%-25% among women and 5%-12% among men. Selective serotonin reuptake inhibitors (SSRIs) are the most used and the most cost-effective treatment for long-term major depressive disorder. Since the introduction of generic SSRIs, the costs of branded drugs have been questioned. The objective of this study was to assess the cost-effectiveness (€ per quality-adjusted life year [QALY]) of escitalopram (which is still covered by a patent) compared with paroxetine, sertraline, and citalopram, the patents for which have expired. METHODS: A decision analytic model was adapted from the Swedish Dental and Pharmaceutical benefits agency model to reflect current clinical practice in the treatment of depression in Italy in collaboration with an expert panel of Italian psychiatrists and health economists. The population comprised patients with a first diagnosis of major depressive disorder and receiving for the first time one of the following SSRIs: escitalopram, sertraline, paroxetine, and citalopram. The time frame used was 12 months. Efficacy and utility data for the original model were validated by our expert panel. Local data were considered for resource utilization and for treatment costs based on the Lombardy region health service perspective. Several scenario simulations, oneway sensitivity analyses, and Monte Carlo simulations were performed to test the robustness of the model. RESULTS: The base case scenario showed that escitalopram had an incremental cost-effectiveness ratio (ICER) of €4395 and €1080 per QALY compared with sertraline and paroxetine, respectively. Escitalopram was dominant over citalopram, which was confirmed by most one-way sensitivity analyses. The escitalopram strategy gained 0.011 QALYs more than citalopram, 0.008 more than paroxetine, and around 0.007 more than sertraline. Monte Carlo simulations indicated that ICER values for escitalopram were centered around €1100 and €4400 per QALY compared with paroxetine and sertraline, respectively. Although there is no official cost-effectiveness threshold in Italy, the value of €25,000 per QALY could be acceptable. All ICER values retrieved in all analyses were lower than this threshold. CONCLUSION: The findings from this cost-effectiveness analysis indicate that escitalopram could be accepted as a cost-effective strategy for the Lombardy region health service compared with the other SSRIs studied. The present assessment is based on ICER values resulting from this analysis, which are lower than the thresholds proposed by health care authorities in other European Union countries. These benefits are driven by the effectiveness of escitalopram, which result in an improved health-related quality of life, a higher probability of sustained remission, and better utilization of health care resources. The study results are robust and in line with other pharmacoeconomic analyses comparing escitalopram with other SSRIs.