Economic Burden of Non-Alcoholic Steatohepatitis (NASH) Among Diabetic Population in Italy: Analysis and Perspectives.

Background: Aim of our study is to evaluate the economic impact of NASH among diabetic population in Italy and potential benefits of treatments that can slow the disease progression. Methods: A Markov model was conducted from the Italian National Healthcare System perspective reporting results at 3, 5, 10 and 15 years. The model included NASH and T2DM patients with all stages of fibrosis (F0-F3), compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC), liver transplant (LT), post-LT and death. A 1-year model cycle length was considered, with each patient passing through the stages and exiting the model when reached one of mortality states. Transition probabilities and annual cost related to health states were derived from published literature. Moreover, the model made it possible to develop a scenario analysis to simulate the impact of treatments capable of slowing the disease progression in phases F0-F4 (CC). Results: The results highlighted an economic burden of NASH in T2DM patients of approximately € 1.4 billion, € 3.1 billion, and € 9.4 billion, respectively, after 3, 5 and 10 years, reaching about € 17.3 billion after 15 years. The slowing down of the progression in the early stages of the disease (fibrosis F0-CC) has led to significant savings corresponding to € 2.3 billion at 15 years. These savings were generated by the reduction of the patients in the advanced stages of the disease, which is linked to a reduction in deaths, equal to 92,208 deaths avoided over a 15-year time horizon. Conclusion: Patients with NASH and T2DM reported an important burden in Italy. It is important to investigate the potential clinical and economic benefits of antidiabetic drugs that have been shown to be effective in preventing the transition to advanced disease, simultaneously acting on the therapeutic goals of diabetic disease.

Probiotic Therapy With VSL#3® in Patients With NAFLD: A Randomized Clinical Trial.

Aim: To evaluate if VSL#3® [a high-concentration multi-strain probiotic mix containing one strain of Streptococcus thermophilus BT01, three strains of Bifidobacteria (B. breve BB02; B. animalis subspecies [subsp.] lactis BL03, previously identified as B. longum BL03; and B. animalis subsp. lactis BI04, previously identified as B. infantis BI04), and four strains of Lactobacilli (L. acidophilus BA05, L. plantarum BP06, L. paracasei BP07, and L. helveticus BD08, previously identified as L. delbrueckii subsp. bulgaricus BD08)] therapy could improve hepatic parameters. Methods: We enrolled 60 Caucasian patients aged ≥ 18 years of either sex with the diagnosis of non-alcoholic fatty liver disease (NAFLD), according to practice guidance, in a double-blind, placebo-controlled study. Patients were randomized to take placebo or VSL#3®, 2 sachets/day in the morning for 3 months. VSL#3® and placebo were self-administered. Results: We did not observe any change in body mass index (BMI), circumferences, fasting plasma glucose (FPG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and adiponectin (ADN) with neither treatment. A statistically significant triglycerides (Tg) decrease (p < 0.05 vs. baseline, and p < 0.05 vs. placebo, respectively) and high-sensitivity C-reactive protein (Hs-CRP) decrease (p < 0.05 vs. baseline) was observed in the group of patients being treated with VSL#3® compared with placebo. Transaminases and gamma-glutamyltransferase (γ-GT) were significantly reduced in VSL#3® group (p < 0.05 vs. baseline and placebo, respectively) compared with the placebo group. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio and hepatic steatosis index (HSI) were significantly lower than the VSL#3® group (p < 0.05 vs. baseline and placebo, respectively) compared with the placebo group. All patients reported an improvement or the disappearance of hepatic steatosis. Conclusion: Probiotic therapy with VSL#3® ameliorates hepatic parameters and echography grading, while reducing Tg and the inflammatory status, without any difference between men and women.

Vitamin D3 supplementation improves glycemic control in type 2 diabetic patients: Results from an Italian clinical trial.

Background: to evaluate the effects of Vitamin D3 on glyco-metabolic control in type 2 diabetic patients with Vitamin D deficiency. Methods: one hundred and seventeen patients were randomized to placebo and 122 patients to Vitamin D3. We evaluated anthropometric parameters, glyco-metabolic control, and parathormone (PTH) value at baseline, after 3, and 6 months. Results: a significant reduction of fasting, and post-prandial glucose was recorded in Vitamin D3 group after 6 months. A significant HbA1c decrease was observed in Vitamin D3 (from 7.6% or 60 mmol/mol to 7.1% or 54 mmol) at 6 months compared to baseline, and to placebo (p < 0.05 for both). At the end of the study period, we noticed a change in the amount in doses of oral or subcutaneous hypoglycemic agents and insulin, respectively. The use of metformin, acarbose, and pioglitazone was significantly lower (p = 0.037, p = 0.048, and p = 0.042, respectively) than at the beginning of the study in the Vitamin D3 therapy group. The units of Lispro, Aspart, and Glargine insulin were lower in the Vitamin D3 group at the end of the study (p = 0.031, p = 0.037, and p = 0.035, respectively) than in the placebo group. Conclusions: in type 2 diabetic patients with Vitamin D deficiency, the restoration of value in the Vitamin D standard has led not only to an improvement in the glyco-metabolic compensation, but also to a reduced posology of some oral hypoglycemic agents and some types of insulin used.

Economic Impact of COVID-19 Lockdown on Italian NHS: Focus on Diabetes Mellitus.

BACKGROUND: In Italy, the adoption of a total lockdown has generated almost total suspension of outpatient visits except for emergencies. Even after lockdown, the pandemic fear created additional barriers to access the health services. The aim of our study is to evaluate the economic impact of the lockdown for COVID-19 on public health in Italy, focusing on its effects on diabetic population. MATERIALS AND METHODS: We analyzed the impact of the lockdown on excess mortality and morbidity in the Italian diabetic population during 2020. The analysis was divided into several steps: a quantification of specialist visit reduction, the calculation of excess mortality in the diabetic population, the economic evaluation of the slowdown in the use of innovative diabetic therapies. Furthermore, the impact of the lockdown on the reduction of procedures and follow-up visits in diabetic population was evaluated. The overall impact of the pandemic and lockdown effects on costs and quality of life was then calculated. RESULTS: During 2020, a drop of 28% in patient access has been observed. Diabetic patients recorded a twice higher mortality value compared to general population (20.4% vs 10.2%). The analysis of market data revealed a slowdown in consumption of new antidiabetic therapies (-14%, 27% vs 41%). We estimated an expense of €26.6 million for NHS and a loss of 257 utilities in diabetic population due to the missed benefits related to slowdown in innovative antidiabetic drugs use and non-optimal follow-up and control of diabetes complications. In simulation scenarios, we also estimated an overall expenditure ranging from €38.7 to 94.0 million and a loss of 294-836 utilities. CONCLUSION: Diabetic population paid a high tribute to pandemic and lockdown, both in terms of number of deaths and burden of diabetic complications, together with an overall deterioration of quality of life.

Cost-Utility Analysis of Saxagliptin/Dapagliflozin Versus Gliclazide and Insulin Glargine: Economic Implications of the Outcomes of the CVD-Real Studies I and II.

Diabetes treatment cost represents an ever-growing problem. The adoption of new drugs in therapy, although they can guarantee an improvement in patient's quality of life, can meet obstacles when it involves an increase in costs. We decided to compare the costs and benefits of the new saxagliptin and dapagliflozin combination versus traditional therapies. Bodyweight loss and the sharp reduction in hypoglycemic episodes were the 2 main clinical outcomes that emerged from registered studies of saxagliptin and dapagliflozin compared with the sulfonylureas. These results, combined with the good cardiovascular risk profile, led to develop a cost-utility analysis. We aimed to show the economic value of this new association therapy. We carried out a cost-utility analysis from the Italian National Healthcare System (NHS) perspective, focused on direct costs related to the treatment and management of main diabetes complications. Utility scores adopted have been measured based on the patient's perception of weight changes. In light of the better durability profile of saxagliptin/dapagliflozin compared with gliclazide, we also considered a simulation scenario to assess the impact on costs of switching to basal insulin, starting from gliclazide and the fixed combination, respectively, and based on the related probabilities to switch. To assess the robustness of the results, a 1-way sensitivity analysis was performed by changing the main parameters by ±20%. Furthermore, the sensitivity of the results was tested considering the addition of a percent discount, because the purchase costs of drugs are usually subject to hidden discounts. We calculated the total direct annual cost per patient of saxagliptin/dapagliflozin versus gliclazide and insulin glargine for patients with type 2 diabetes mellitus not achieving glycemic control on metformin plus saxagliptin alone, dapagliflozin alone, or gliclazide at a lower dosage. Total treatment costs have been obtained adding the direct cost of the drug, needles, glycemic self-monitoring, hypoglycemic events, cardiovascular complications, and effect on consumption of other drugs. The total direct cost of saxagliptin/dapagliflozin fixed dose combination was €414.62 higher than gliclazide (€1.067.72 vs €653.10), and greater than basal insulin, with a difference of €166.99 (€1067.72 vs €900.72). Despite the higher annual direct total cost, the additional cost per quality-adjusted life year (QALY) gained, compared with gliclazide, has been €11 517, and €4639, when compared with insulin glargine in the base-case scenario, and the robustness of the results has been shown in the sensitivity analysis. The results of our cost-utility analysis, expressed as incremental cost-effectiveness ratios, were fully compliant with the threshold adopted for Italy. Then, saxagliptin/dapagliflozin can be considered a cost-effective oral hypoglycemic agent. The positive effect of this drug on the quality of life, induced by the bodyweight loss, has allowed this outcome, despite the higher annual cost per patient, mainly determined by the drug purchase cost.

Economic Evaluation of Dulaglutide vs Traditional Therapies: Implications of the Outcomes of the Rewind Study.

BACKGROUND: Diabetes represents a relevant public health problem worldwide due to its growing prevalence and socioeconomic burden, principally due to the development of macrovascular and microvascular complications as well as to the continuous launch of new and even more expensive drugs. The aim of our study is to evaluate the economic impact of dulaglutide, a weekly GLP-1 receptor agonist, on the treatment of diabetic patients as an alternative to both high dose sulphonylureas and insulin basalization at the failure of oral therapies alone. We carried out a cost-effectiveness analysis developed considering the economic implications of recent clinical studies regarding cardiovascular risk drug effects and especially of REWIND studies outcomes, focusing on the impact of weight changes on HRQoL. MATERIAL AND METHOD: In our analysis, we have applied the cost-utility technique to the above reported clinical outcomes and compared the global costs of dulaglutide versus sulfonylurea or basal insulin, all in add-on with metformin. We have chosen gliclazide, as a sulfonylurea and Abasaglar®, the less expensive among basal insulin analogues. Abasaglar was titrated to 20 IU, corresponding to the mean dosage used in the treatment of type II diabetic patients. The model aims to estimate total direct costs related to the above-reported treatments and find out the real gap in costs between dulaglutide, the apparently cheaper gliclazide and basal insulin glargine (IGlargine) based on the Italian National Healthcare System (INHS). RESULTS: The total cost of dulaglutide has resulted in €859.66 higher than gliclazide (€1,579.73 vs €720.07) and basal insulin, although less significantly, reporting a difference of €396.54 (€1,579.73 vs 1,183.19). Except for the purchase cost, dulaglutide has reported reduced costs compared to insulin IGlargine and gliclazide. Dulaglutide showed lower self-monitoring blood glucose and hypoglycaemia costs, a significant reduction in costs related to cardiovascular complications, as well as savings in costs in other drugs. Dulaglutide can be considered a cost-effective antidiabetic therapy, due to the positive impact on the quality of life induced by weight reduction, despite the higher annual cost per patient, mainly influenced by drug purchase cost. DISCUSSION AND CONCLUSION: In this cost-utility analysis, dulaglutide has shown to be a cost-effective treatment option from the Italian healthcare system perspective as add-on therapy to metformin in patients with inadequately controlled type 2 diabetes mellitus. Study findings can provide stakeholders valuable evidence to support the adoption of this cost-effective second- or third-line therapy compared to gliclazide or basal insulin glargine. Dulaglutide cost-effectiveness has been particularly evident in the comparison with basal insulin glargine, indicating that, in patients who have treatment indication, this therapy may be preferred to basalization avoiding related complications and costs.

Omalizumab for Severe Allergic Asthma Treatment in Italy: A Cost-Effectiveness Analysis from PROXIMA Study.

INTRODUCTION: Inadequately controlled severe asthma patients require additional therapy accounting for significant clinical and economic burden. Our analysis aims to determine the cost-effectiveness of omalizumab in the management of severe allergic asthma in Italy based on observational data from the PROXIMA study. METHODS: Observational data on efficacy, healthcare resource utilization and changes in quality of life at 12 months after the initiation of omalizumab were examined to estimate the cost-effectiveness compared to pre-omalizumab period and results were expressed with Incremental Cost-Effectiveness Ratio (ICER). The cost-utility analysis estimated the cost per quality-adjusted life-year (QALY) gained. Direct health costs were assessed from the perspective of the Italian National Health Service (NHS). RESULTS: Omalizumab reduced the incidence of exacerbations, number of hospitalizations, physician visits, and improved quality of life after 12 months of treatment. Omalizumab had a greater effectiveness than pre-omalizumab treatment involving 0.132 QALYs gained and led to a €3729 per patient reduction in direct healthcare costs, excluding the add-on treatment cost. Nevertheless, the addition of omalizumab cost led to €7478 increase in total direct costs with respect to pre-omalizumab period. Based on difference in total direct cost and difference in QALY between post and pre-omalizumab period, the ICER was €56,847. According to sensitivity analysis, omalizumab provided a cost-effective use of NHS resources, already at 20% discounted price. CONCLUSION: This study offers a real-world evidence of omalizumab effectiveness in Italy. Despite the high acquisition cost of the innovative drug, omalizumab is a sustainable treatment option for patients with uncontrolled severe allergic asthma.

Omalizumab and long-term quality of life outcomes in patients with moderate-to-severe allergic asthma: a systematic review.

BACKGROUND: Asthma is a highly prevalent chronic inflammatory airways disease, with a considerable impact on quality of life (QoL). To express the effects of asthma on patients' subjective experience, patient-reported outcomes (PROs) represent an important instrument. The asthma QoL questionnaire (AQLQ) is one of the main PROs among these. MATERIALS AND METHODS: To identify long-term asthma-related QoL outcomes associated with omalizumab therapy in patients with moderate-to-severe asthma, we developed a systematic review according to the PRISMA guidelines. Published real-world effectiveness studies of adults or adolescents (12 years or older) with moderate-to-severe allergic asthma treated with omalizumab for at least 48 weeks were reviewed. Sources used were Medline ( PubMed), the Cochrane Library and Google Scholar up to February 2018. In addition, a cross-referencing search was conducted to complete the revision. RESULTS: A total of 255 potential papers were identified in the first search through the database. After full-text viewing, eight articles were finally included in the review. We summarized the results according to the study design, patient baseline characteristics and effectiveness outcomes assessed by AQLQ score results: variation from baseline to the end of study. Results confirmed the long-term benefits of omalizumab as an add-on therapy in patients with uncontrolled moderate-to-severe allergic asthma. Since there is a lot of evidence on omalizumab effectiveness, we aimed to focus on how a therapy can change patient's QoL in a long time period. Data showed long-term effects of omalizumab treatment on subjective (PROs) and objective (lung function, corticosteroid use, hospitalizations, asthma exacerbation) effectiveness measures. CONCLUSION: Studies included in our review were observational trials that, due to their design, present a potential risk of selection bias in the patients included. Beyond this limit, the evaluation of QoL using the AQLQ showed a clear increase over time, following both 48 weeks and 9 years of observation, where QoL improvements still were significant over baseline values.

Shadow cost of oral corticosteroids-related adverse events: A pharmacoeconomic evaluation applied to real-life data from the Severe Asthma Network in Italy (SANI) registry.

BACKGROUND: Asthma is one of the most common non-communicable respiratory diseases, affecting about 6% of the general population. Severe asthma, even if afflicts a minority of asthmatics, drives the majority of costs of the disease. The aim of this study is to create a pharmacoeconomic model to predict the costs of corticosteroid-related adverse events in severe asthmatics and applying it to the first published epidemiologic data from the Severe Asthma Network in Italy (SANI) registry. METHODS: The analysis was conducted from the perspective of the Italian National Healthcare System (INHS). Model inputs, derived from literature, included: asthma epidemiology data, frequency of adverse events, percentage of severe asthma treated with OCS and adverse event cost (Diagnosis-Related Group (DRG) national tariffs). We estimated costs per different patient groups: non-asthma controls, mild/moderate and severe asthmatics. Final results report estimated direct cost per patient and total direct cost for overall target population, showing economic impact related to corticosteroid complication. RESULTS: Based on epidemiological data input, in Italy, asthmatic subjects resulted about 3,999,600, of which 199,980 with severe asthma. The number of patients with severe asthma OCS-treated was estimated at 123,988. Compared to the non-asthma control cohort and to that with moderate asthma annual cost per severe asthmatic patient resulted respectively about €892 and €606 higher, showing a corticosteroids shadow cost ranging from 45% to 30%.Applying the cost per patient to the target population identified for Italy, the budget impact model estimated a total annual cost related to OCS-related adverse events of €242.7 million for severe asthmatics. In respect with non-asthmatic and moderate population, an incremental expenditure of about € 110.6 million and €75.2, respectively, were shown. CONCLUSIONS: Our study provides the first estimates of additional healthcare costs related to corticosteroid induced adverse events in severe asthma patient. Budget impact model results highlighted the relevant economic impact of OCS-related adverse events in severe asthma patients. The future extrapolation of additional data from SANI registry will support the development of a model to investigate the role of corticosteroids sparing drugs.

Budget impact model of secukinumab for the treatment of moderate-to-severe psoriasis, psoriatic arthritis, and ankylosing spondylitis in Italy: a cross-indication initiative.

OBJECTIVE: Secukinumab, a fully human monoclonal IgG1 antibody that selectively neutralizes the proinflammatory cytokine IL-17A, has been approved in Europe in 2015 for the treatment of adult patients with moderate-to-severe plaque psoriasis, psoriatic arthritis (PsA), and ankylosing spondylitis (AS). This analysis assessed the budget impact of introduction of secukinumab to the Italian market for all three indications from the perspective of the Italian National Health Service. MATERIALS AND METHODS: A cross-indication budget impact model was developed and included biologic-treated adult patients diagnosed with psoriasis, PsA, and AS. The analyses were conducted over a 3-year time horizon and included direct costs (drug therapy costs, administration costs, diseases-related costs, and adverse events costs). Model input parameters (epidemiology, market share projections, resource use, and costs) were obtained from the published literature and other Italian sources. The robustness of the results was tested via one-way sensitivity analyses: secukinumab cost, secukinumab market share, intravenous administration costs, and adverse events costs were varied by ±10%. RESULTS: The total patient population for secukinumab over the 3-year timeframe was projected to be 6,648 in the first year, increasing to 12,001 in the third year, for all three indications combined (psoriasis, PsA, and AS). Compared to a scenario without secukinumab in the market, the introduction of secukinumab in the market for the treatment of psoriasis, PsA, and AS showed a cumulative 3-year incremental budget impact of -5%, corresponding to savings of €66.1 million and per patient savings of about €1,855. The majority of the cost savings came from the adoption of secukinumab in AS (58%), followed by PsA (29%) and psoriasis (13%). Sensitivity analyses confirmed the robustness of the results. CONCLUSION: Results from this cross-indication budget impact model show that secukinumab is a cost-saving option for the treatment of PsA, AS, and psoriasis patients in Italy.

Cost-minimization analysis of degludec/liraglutide versus glargine/aspart: economic implications of the DUAL VII study outcomes.

BACKGROUND: Diabetes represents a relevant public health problem worldwide due to its increasing prevalence and socioeconomic burden. There is no doubt that tight glycemic control reduces the development of diabetic complications such as the long-term costs related to the disease. The aim of our model was to calculate total direct costs associated with the two treatments considered in DUAL VII study, and hence evaluate the potential economic benefits for the National Health System (NHS) deriving from the use of insulin degludec plus liraglutide (IDegLira) in a once-daily fixed combination. MATERIALS AND METHODS: We applied the cost-minimization technique adopting the NHS point of view to the DUAL VII trial outcomes. In the model, developed in Microsoft Excel®, we calculated and compared annual costs per patient of the two therapeutic options for type 2 diabetes (T2D) patients not achieving glycemic control on basal insulin and metformin described in the trial, including costs of therapy management and side effects, both negative and positive. Annual treatment costs were calculated based on IDegLira and basal bolus end-of-trial doses resulting in a 1:2 ratio (40.4 U vs 84.1 U). Therefore, maintaining the IDegLira/basal bolus at 1:2 dose ratio, we calculated the correlation between the dose reduction and costs compared to DUAL VII doses base case scenario. RESULTS: Total treatment costs were obtained by adding annual cost of drug, needles, glycemic self-monitoring, hypoglycemic events, and effect on consumption of other drugs. Total annual costs of IDegLira combination resulted in €434 higher than basal bolus in DUAL VII base case (40.4 U); the two treatments reported equal costs at 34% dose reduction (26.7 U), while below this value IDegLira treatment became less expensive, with about €215 gain at 50% dose reduction (20.2 U). It is also important to notice that above the break-even point, until an IDegLira dose of 30 U, the cost difference is negligible in view of the clinical benefit provided by the fixed combination highlighted in DUAL VII trial. CONCLUSION: Adding the significant clinical findings derived from DUAL VII trial to our economic evaluation, IDegLira seems to offer an important alternative to basal-bolus therapy.

The preventive effect on respiratory tract infections of Oscillococcinum®. A cost-effectiveness analysis.

BACKGROUND: Anas barbariae hepatis et cordis extractum 200K (Oscillococcinum®) is used to treat and prevent seasonal colds and airway inflammatory affections, improve symptom control, and reduce the frequency of respiratory tract infection (RTI) episodes. The objective of this controlled observational study is to investigate, from the Italian National Health Service (NHS) point of view, the role of Anas barbariae hepatis et cordis extractum 200K in preventing RTIs and estimate the annual average cost per patient due to visits and medicines in a real-world setting, investigating whether this method of treatment can bring savings for the NHS. METHODS: Data from a single center from 2002 to 2011 were used. The analysis examined 455 patients who suffered from respiratory diseases. Of the total number of patients, 246 were treated with Anas barbariae hepatis et cordis extractum 200K while 209 were not treated (Control group). All the data concerning RTI episodes, pharmacological treatments, and pneumological visits were extracted from the database. RESULTS: It was found that, regardless of the diagnosis, the frequency of RTI episodes was always lower in patients treated with Anas barbariae hepatis et cordis extractum 200K; the difference between the numbers of events occurring was statistically significant in every class of patients (p<0.001). The costs that the NHS had to incur were significantly lower in the classes of patients treated (p<0.001). DISCUSSION: The results indicate that Anas barbariae hepatis et cordis extractum 200K has a preventive effect on the onset of RTI episodes. The analysis shows that treating patients with Anas barbariae hepatis et cordis extractum 200K lowers costs for the NHS; this is primarily due to the fact that the medication causes fewer episodes of RTI to develop. This study suggests that the treatment with Anas barbariae hepatis et cordis extractum 200K could be helpful in preventing RTIs and improving the health status of patients who suffer from respiratory diseases, and it could lead to savings to the Italian NHS.