Bridges Between Spiking Neural Membrane Systems and Virus Machines.

Spiking Neural P Systems (SNP) are well-established computing models that take inspiration from spikes between biological neurons; these models have been widely used for both theoretical studies and practical applications. Virus machines (VMs) are an emerging computing paradigm inspired by viral transmission and replication. In this work, a novel extension of VMs inspired by SNPs is presented, called Virus Machines with Host Excitation (VMHEs). In addition, the universality and explicit results between SNPs and VMHEs are compared in both generating and computing mode. The VMHEs defined in this work are shown to be more efficient than SNPs, requiring fewer memory units (hosts in VMHEs and neurons in SNPs) in several tasks, such as a universal machine, which was constructed with 18 hosts less than the 84 neurons in SNPs, and less than other spiking models discussed in the work.

Multitask Adversarial Networks Based on Extensive Nonlinear Spiking Neuron Models.

Deep learning technology has been successfully used in Chest X-ray (CXR) images of COVID-19 patients. However, due to the characteristics of COVID-19 pneumonia and X-ray imaging, the deep learning methods still face many challenges, such as lower imaging quality, fewer training samples, complex radiological features and irregular shapes. To address these challenges, this study first introduces an extensive NSNP-like neuron model, and then proposes a multitask adversarial network architecture based on ENSNP-like neurons for chest X-ray images of COVID-19, called MAE-Net. The MAE-Net serves two tasks: (i) converting low-quality CXR images to high-quality images; (ii) classifying CXR images of COVID-19. The adversarial architecture of MAE-Net uses two generators and two discriminators, and two new loss functions have been introduced to guide the optimization of the network. The MAE-Net is tested on four benchmark COVID-19 CXR image datasets and compared them with eight deep learning models. The experimental results show that the proposed MAE-Net can enhance the conversion quality and the accuracy of image classification results.

Key considerations for modelling the long-term costs and benefits of treatments for ANCA-associated vasculitis.

OBJECTIVES: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of severe and chronic autoimmune diseases. Patients undergo two treatment phases: inducing remission and maintaining remission to prevent organ damage. Immunosuppressants, including glucocorticoids (GCs) are used as first-line treatment, but long-term GC use is associated with toxic effects. Novel treatments reduce or replace the need for long-term GC, and therefore can reduce GC-related toxicity. The evolving treatment landscape has presented new challenges for health technology assessment (HTA) of new treatments in AAV and long-term modelling of costs and outcomes in this disease. METHODS: Using the appraisal of avacopan in England (NICE) as a case study, this paper aims to identify the key challenges involved in the economic evaluation of new treatments for AAV, with a particular focus on the long-term modelling of the treatment costs and benefits for the purpose of HTA. The outcome of this study is a set of recommendations for modelling the cost-effectiveness of new treatments for AAV from the HTA perspective. RESULTS: The discussion focuses on the appropriate model structure, approach to modelling end-stage renal disease (ESRD) as a key determinant of costeffectiveness, capturing the impact of GC-related adverse events, and estimation of short and long-term costs of AAV. CONCLUSIONS: Economic evaluation of new treatments for AAV needs to capture all relevant downstream effects. ESRD is a key driver of cost-effectiveness but is associated with major uncertainty. Future observational studies need to offer sufficient detail to allow for differentiation in event rates across treatment options.

A Parallel Convolutional Network Based on Spiking Neural Systems.

Deep convolutional neural networks have shown advanced performance in accurately segmenting images. In this paper, an SNP-like convolutional neuron structure is introduced, abstracted from the nonlinear mechanism in nonlinear spiking neural P (NSNP) systems. Then, a U-shaped convolutional neural network named SNP-like parallel-convolutional network, or SPC-Net, is constructed for segmentation tasks. The dual-convolution concatenate (DCC) and dual-convolution addition (DCA) network blocks are designed, respectively, in the encoder and decoder stages. The two blocks employ parallel convolution with different kernel sizes to improve feature representation ability and make full use of spatial detail information. Meanwhile, different feature fusion strategies are used to fuse their features to achieve feature complementarity and augmentation. Furthermore, a dual-scale pooling (DSP) module in the bottleneck is designed to improve the feature extraction capability, which can extract multi-scale contextual information and reduce information loss while extracting salient features. The SPC-Net is applied in medical image segmentation tasks and is compared with several recent segmentation methods on the GlaS and CRAG datasets. The proposed SPC-Net achieves 90.77% DICE coefficient, 83.76% IoU score and 83.93% F1 score, 86.33% ObjDice coefficient, 135.60 Obj-Hausdorff distance, respectively. The experimental results show that the proposed model can achieve good segmentation performance.

Attacking cryptosystems by means of virus machines.

The security that resides in the public-key cryptosystems relies on the presumed computational hardness of mathematical problems behind the systems themselves (e.g. the semiprime factorization problem in the RSA cryptosystem), that is because there is not known any polynomial time (classical) algorithm to solve them. The paper focuses on the computing paradigm of virus machines within the area of Unconventional Computing and Natural Computing. Virus machines, which incorporate concepts of virology and computer science, are considered as number computing devices with the environment. The paper designs a virus machine that solves a generalization of the semiprime factorization problem and verifies it formally.

Profile, Healthcare Resource Consumption and Related Costs in ANCA-Associated Vasculitis Patients: A Real-World Analysis in Italy.

INTRODUCTION: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are rare autoimmune diseases triggering inflammation of small vessels. This real-world analysis was focused on the most common AAV forms, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), to describe patients' demographic and clinical characteristics, therapeutic management, disease progression, and the related economic burden. METHODS: A retrospective analysis was conducted on administrative databases of a representative sample of Italian healthcare entities, covering approximately 12 million residents. Between January 2010 and December 2020, adult GPA patients were identified by payment waiver code or hospitalization discharge diagnosis, and MPA patients by payment waiver code with or without hospitalization discharge diagnosis. Clinical outcomes were evaluated through AAV-related hospitalizations, renal failure onset, and mortality. Economic analysis included healthcare resource utilization deriving from drugs, hospitalizations, and outpatient specialist services. The related mean direct costs year/patient were also calculated in patients stratified by presence/absence of glucocorticoid therapy and type of inclusion criterion (hospitalization/payment waiver code). RESULTS: Overall, 859 AAV patients were divided into GPA (n = 713; 83%) and MPA (n = 146; 17%) cohorts. Outcome indicators highlighted a clinically worse phenotype associated with GPA compared to MPA. Cost analysis during follow-up showed tendentially increased expenditures in glucocorticoid-treated patients versus untreated (overall AAV: €8728 vs. €7911; GPA: €9292 vs. €9143; MPA: €5967 vs. €2390), mainly driven by drugs (AAV: €2404 vs. €874; GPA: €2510 vs. €878; MPA: €1881 vs. €854) and hospitalizations. CONCLUSION: Among AAV forms, GPA resulted in a worse clinical picture, higher mortality, and increased costs. This is the first real-world pharmaco-economic analysis on AAV patients stratified by glucocorticoid use on disease management expenditures. In both GPA and MPA patients, glucocorticoid treatment resulted in higher healthcare costs, mostly attributable to medications, and then hospitalizations, confirming the clinical complexity and economic burden for management of patients with autoimmune diseases under chronic immunosuppression.

Using Virus Machines to Compute Pairing Functions.

Virus machines are computational devices inspired by the movement of viruses between hosts and their capacity to replicate using the resources of the hosts. This behavior is controlled by an external graph of instructions that opens different channels of the system to make viruses capable of moving. This model of computation has been demonstrated to be as powerful as turing machines by different methods: by generating Diophantine sets, by computing partial recursive functions and by simulating register machines. It is interesting to investigate the practical use cases of this model in terms of possibilities and efficiency. In this work, we give the basic modules to create an arithmetic calculator. As a practical application, two pairing functions are calculated by means of two different virus machines. Pairing functions are important resources in the field of cryptography. The functions calculated are the Cantor pairing function and the Gödel pairing function.

Clinical and economic impact of ferric carboxymaltose treatment for iron deficiency in patients stabilized following acute heart failure: a multinational study.

OBJECTIVE: To estimate clinical events and evaluate the financial implications of introducing ferric carboxymaltose (FCM) to treat iron deficiency (ID) at discharge in patients hospitalized for acute heart failure (AHF) with left ventricular ejection fraction (LVEF) <50% in the UK, Switzerland and Italy. METHODS: A decision analytic cost-offset model was developed to evaluate the costs associated with introducing FCM for all eligible patients in three countries compared to a world without FCM, over a five-year time horizon. Data from AFFIRM-AHF clinical trial were used to model clinical outcomes, using an established cohort state-transition Markov model. Country-specific prevalence estimates were derived using data from real-world studies to extrapolate number of events and consequent cost totals to the population at risk on a national scale. RESULTS: The cost-offset modeling demonstrated that FCM is projected to be a cost-saving intervention in all three country settings over a five-year time horizon. Savings were driven primarily by reduced hospitalizations and avoided cardiovascular deaths, with net cost savings of -£14,008,238, -CHF25,456,455 and -€105,295,146 incurred to the UK, Switzerland and Italy, respectively. LIMITATIONS: Although AFFIRM-AHF was a multinational trial, efficacy data per country was not sufficiently large to enable country-specific analysis, therefore overall clinical parameters have been assumed to apply to all countries. CONCLUSIONS: This study provides further evidence of the potential cost savings achievable by treating ID with FCM at discharge in patients hospitalized for AHF with LVEF <50%. The value of FCM treatment within the healthcare systems of the UK, Switzerland and Italy was demonstrated even within a limited time frame of one year, with consistent cost savings indicated over a longer term.

Incidence, Treatment and Clinical Impact of Iron Deficiency in Chronic Heart Failure: A Longitudinal Analysis.

In patients with heart failure (HF), iron deficiency (ID) is a well-recognized therapeutic target; information about its incidence, patterns of iron repletion, and clinical impact is scarce. This single-centre longitudinal cohort study assessed the rates of ID testing and diagnosis in patients with stable HF, patterns of treatment with intravenous iron, and clinical impact of intravenous iron on HF rehospitalization risk. We included 711 consecutive outpatients (4400 visits) with stable chronic HF from 2014 to 2019 (median [interquartile range] visits per patient: 2 [2−7]. ID was defined as serum ferritin <100 µg/L, or 100−299 µg/L with transferrin saturation (TSAT) < 20%. During a median follow-up of 2.20 (1.11−3.78) years, ferritin and TSAT were measured at 2230 (50.7%) and 2183 visits (49.6%), respectively. ID was found at 846 (37.9%) visits, with ferritin and TSAT available (2230/4400), and intravenous iron was administered at 321/4400 (7.3%) visits; 233 (32.8%) patients received intravenous iron during follow-up. After multivariate analyses, iron repletion at any time during follow-up was associated with a lower risk of recurrent HF hospitalization (hazard ratio [HR] = 0.50, 95% confidence interval [CI] = 0.28−0.88; p = 0.016). Thus, ID was a frequent finding in patients with HF, and its repletion reduced the risk of recurrent HF hospitalizations.

A cost-effectiveness analysis of patiromer for the treatment of hyperkalemia in chronic kidney disease patients with and without heart failure in Spain.

AIMS: Renin-angiotensin-aldosterone system inhibitors (RAASi) therapy is commonly used to reduce the risk of death and to slow down disease progression in patients with chronic kidney disease (CKD), heart failure (HF) and hypertension. However, the cardio-renal benefits of RAASi therapy are also associated with an increased risk of hyperkalemia (HK), which may lead to dose reduction or discontinuation of therapy. Patiromer has demonstrated to reduce the risk of HK, which enables to maintain optimal doses of RAASi therapy. This study aimed to assess the cost-effectiveness of patiromer for the management of HK in CKD patients with and without HF in Spain. METHODS: A Markov model was developed to evaluate the costs and benefits of patiromer for the management of HK in patients with CKD stages 3-4 with and without HF treated with RAASi over a lifetime horizon. The main outcomes included total direct costs (€2021), quality-adjusted life-years (QALYs), life-years gained (LYG) and incremental cost-effectiveness ratio (ICER). Deterministic one-way and probabilistic sensitivity analyses were performed to assess the robustness of the results. RESULTS: Patiromer was more effective compared to no patiromer (5.76 vs 5.57 QALYs; 7.73 vs 7.50 LYG), and resulted in an incremental cost of €3,574, yielding an ICER of €19,092/QALY gained and of €15,236/LYG. Sensitivity analyses suggested that the results were robust to changes in most input parameters. CONCLUSIONS: Patiromer is a cost-effective intervention in maintaining normokalemia and enabling optimal RAASi therapy in patients with CKD stages 3-4 with and without HF in Spain.

Estimating hospital inpatient cost-savings with sucroferric oxyhydroxide in patients on chronic hemodialysis in five European countries: a cost analysis.

AIMS: Hyperphosphatemia is common among patients with advanced chronic kidney disease (CKD) undergoing dialysis. The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SO), has a low daily pill burden and is indicated for the control of serum phosphorus in these patients. In a retrospective database study, hemodialysis patients switched to long-term SO therapy had fewer hospitalizations compared with patients switched to other PB therapies. This economic analysis aimed to quantify potential cost-savings of reduced hospitalizations associated with SO for healthcare systems in five European countries. MATERIALS AND METHODS: All-cause hospital admissions incidence data were sourced from a real-world retrospective database study comparing adult, in-center hemodialysis patients maintained on 2 years of SO therapy (mSO) versus patients who discontinued SO (dSO) within 90 days of their first prescription and switched to other PBs. A literature search was conducted to determine the cost per hospital admission for dialysis patients in the healthcare setting of each European country. A cost-model combined the incidence rate of all-cause hospital admissions and the cost per admission to estimate the country-specific inpatient costs for the mSO and dSO groups. RESULTS: Annual inpatient cost-savings per patient in the mSO group versus the dSO group were €1,201, €2,097, €2,059, €1,512, and €3,068 in France, Germany, Italy, Spain, and the UK, respectively. When annual PB drug costs per patient were considered, the net annual economic cost-savings per patient were €327, €1,585, €1,022, €1,100, and €2,204, respectively. LIMITATIONS: Hospital admissions data used in the analysis were observational in nature and derived from a US hemodialysis patient population; the effect of SO therapy on hospitalization rates for US and European hemodialysis patients may differ. The analysis did not consider indirect healthcare costs associated with hospitalizations. CONCLUSION: SO therapy may offer substantial inpatient cost-savings by reducing all-cause hospital admissions attributable to uncontrolled hyperphosphatemia.

Ferric carboxymaltose for the treatment of iron deficiency in heart failure: a multinational cost-effectiveness analysis utilising AFFIRM-AHF.

AIMS: Iron deficiency is common in patients with heart failure (HF). In AFFIRM-AHF, ferric carboxymaltose (FCM) reduced the risk of hospitalisations for HF (HHF) and improved quality of life vs. placebo in iron-deficient patients with a recent episode of acute HF. The objective of this study was to estimate the cost-effectiveness of FCM compared with placebo in iron-deficient patients with left ventricular ejection fraction <50%, stabilised after an episode of acute HF, using data from the AFFIRM-AHF trial from Italian, UK, US and Swiss payer perspectives. METHODS AND RESULTS: A lifetime Markov model was built to characterise outcomes in patients according to the AFFIRM-AHF trial. Health states were defined using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Subsequent HHF were incorporated using a negative binomial regression model with cardiovascular and all-cause mortality incorporated via parametric survival analysis. Direct healthcare costs (2020 GBP/USD/EUR/CHF) and utility values were sourced from published literature and AFFIRM-AHF. Modelled outcomes indicated that treatment with FCM was dominant (cost saving with additional health gains) in the UK, USA and Switzerland, and highly cost-effective in Italy [incremental cost-effectiveness ratio (ICER) EUR 1269 per quality-adjusted life-year (QALY)]. Results were driven by reduced costs for HHF events combined with QALY gains of 0.43-0.44, attributable to increased time in higher KCCQ states (representing better functional outcomes). Sensitivity and subgroup analyses demonstrated data robustness, with the ICER remaining dominant or highly cost-effective under a wide range of scenarios, including increasing treatment costs and various patient subgroups, despite a moderate increase in costs for de novo HF and smaller QALY gains for ischaemic aetiology. CONCLUSION: Ferric carboxymaltose is estimated to be a highly cost-effective treatment across countries (Italy, UK, USA and Switzerland) representing different healthcare systems.

Iron Formulations for the Treatment of Iron Deficiency Anemia in Patients with Inflammatory Bowel Disease: A Cost-Effectiveness Analysis in Switzerland.

INTRODUCTION: Iron deficiency anemia (IDA) is a common complication of inflammatory bowel disease (IBD) and can result in reduced quality of life and increased healthcare costs. IDA is treated with iron supplementation, either with oral iron therapy (OI) or intravenous iron formulations, including ferric carboxymaltose (FCM), iron isomaltoside 1000 (IIM), and iron sucrose (IS). This analysis compared the cost-effectiveness of FCM versus IIM, IS, and OI in terms of additional cost per additional responder in Switzerland. METHODS: A health economic model was developed to assess the additional cost per additional responder, defined as normalization or an increase of at least 2 g/dL in hemoglobin levels, for FCM versus IIM, IS, and OI. To date, no single head-to-head trial comparing all therapies is available, and therefore relative efficacy data were taken from a published network meta-analysis. Costs of treatment were calculated in 2020 Swiss francs (CHF) using a microcosting approach, and included the costs of iron, healthcare professional time, and consumables. Costs are also presented in euros (EUR) based on an exchange rate of CHF 1 = EUR 0.94. RESULTS: Response rates with FCM, IIM, IS, and OI were 81%, 74%, 75%, and 69%, respectively, with FCM projected to be the most effective treatment. FCM was associated with cost savings of CHF 24 (EUR 23) versus IIM and of CHF 147 (EUR 138) versus IS, and increased costs by CHF 345 (EUR 324) versus OI. Therefore FCM was considered dominant versus both IIM and IS, improving clinical outcomes with cost savings. FCM was associated with an incremental cost-effectiveness ratio of CHF 2970 (EUR 2792) per additional responder versus OI. CONCLUSIONS: FCM was projected to be the most cost-effective intravenous iron therapy in Switzerland, increasing the number of responders and leading to cost savings for healthcare payers.

Estimating the Epidemiological and Economic Impact of Implementing Preoperative Anaemia Measures in the German Healthcare System: The Health Economic Footprint of Patient Blood Management.

INTRODUCTION: This study aimed to quantify the potential epidemiological and health economic benefits of implementing preoperative anaemia measures (PAMs) in clinical practice in the German healthcare system. METHODS: An evidence-based health economic model was developed to assess the possible impact of implementing PAMs, the first pillar of patient blood management (PBM), in a German population. The analysis of two risk factors-iron-deficiency anaemia (IDA) and receipt of a red blood cell concentrate (RBC) transfusion during elective surgery-allowed the estimation of relative risks (RRs), average cost per patient, average length of hospital stay, and avoided hospital deaths after the implementation of PAMs. RESULTS: A total of 4,591,060 patients who had undergone elective surgery during 2015 were identified, of which 29,170 (0.64%) were diagnosed with preoperative IDA. These patients had an increased RR of receiving a RBC transfusion during surgery (RR 5.031; 95% confidence interval [CI] 4.928, 5.136) and increased mortality risk (RR 3.630; 95% CI 3.401, 3.874) versus patients without IDA. Patients who received a RBC transfusion during surgery had a 24.6-times higher risk of death than those who did not (RR 24.593; 95% CI 24.121, 25.075). Average cost of treatment was €7883 in patients with IDA, €21,744 in patients with IDA and RBC transfusion, and €4560 in patients without risk factors. The model identified 29,714 patients (0.65%) who had received a RBC transfusion and who potentially had IDA but remained undiagnosed before surgery. Hypothetical implementation of PAMs would have resulted in an estimated annual net hospital direct cost saving of €1029 million (1.58%) of total hospital direct costs of the German healthcare system and 3036 hospital deaths (0.07%) avoided. CONCLUSIONS: This model estimated the impact of implementing PAMs for patients with IDA undergoing elective surgery. A significant number of deaths, costly treatments, and hospital days could have been avoided by the introduction of PAMs in routine clinical practice in Germany.

Cost-effectiveness analysis of IDegLira versus basal-bolus insulin for patients with type 2 diabetes in the Slovak health system.

AIMS: To investigate the cost-effectiveness of once-daily insulin degludec/liraglutide (IDegLira) versus basal-bolus therapy in patients with type 2 diabetes not meeting glycemic targets on basal insulin from a healthcare payer perspective in Slovakia. METHODS: Long-term clinical and economic outcomes for patients receiving IDegLira and basal-bolus therapy were estimated using the IMS CORE Diabetes Model based on a published pooled analysis of patient-level data. RESULTS: IDegLira was associated with an improvement in quality-adjusted life expectancy of 0.29 quality-adjusted life years (QALYs) compared with basal-bolus therapy. The average lifetime cost per patient in the IDegLira arm was EUR 2,449 higher than in the basal-bolus therapy arm. Increased treatment costs with IDegLira were partially offset by cost savings from avoided diabetes-related complications. IDegLira was highly cost-effective versus basal-bolus therapy with an incremental cost-effectiveness ratio of EUR 8,590 per QALY gained, which is well below the cost-effectiveness threshold set by the law in Slovakia. CONCLUSION: IDegLira is cost-effective in Slovakia, providing a simple option for intensification of basal insulin therapy without increasing the risk of hypoglycemia or weight gain and with fewer daily injections than a basal-bolus regimen.

The Economic Burden of Insulin-Related Hypoglycemia in Spain.

INTRODUCTION: An analysis was conducted to estimate the economic burden of insulin-related hypoglycemia in adults in Spain, derived from a novel concept developed for the UK known as the Local Impact of Hypoglycemia Tool. METHODS: Costs per severe and non-severe hypoglycemic episode were calculated for patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM). The costs per episode were applied to the population of adults with T1DM and T2DM using insulin in Spain according to the number of severe and non-severe episodes experienced per year. Costs were calculated using Spanish-specific resource costs and published values for resource utilization, including ambulance, accident and emergency (A&E) department, hospitalization, healthcare professional visits, and extra self-monitoring of blood glucose (SMBG) tests used in the week following the episode. A one-way sensitivity analysis on all model inputs was then performed. RESULTS: The cost of insulin-related hypoglycemia in Spain is estimated as €662.0 m per year, €292.6 m of which is due to severe episodes and €369.4 m to non-severe episodes. The cost per episode varies from €1.25 for patients with T1DM and €1.48 for patients with T2DM for a non-severe episode where extra SMBG testing after the episode is the only action taken, to €4378.22 for T1DM and €3005.74 for T2DM for a severe episode that was treated in hospital and requires an ambulance, A&E visit, hospitalization, and a diabetes specialist visit. A reduction in severe and non-severe hypoglycemia rates of just 20% could lead to considerable cost savings of €284,925 per 100,000 general population. CONCLUSION: This analysis highlights the substantial economic burden of hypoglycemia in Spain, and gives budget holders the ability to assess the costs of new treatments or patient education programs in relation to the potential cost savings due to lower hypoglycemia rates.

Cost-effectiveness analysis of insulin degludec compared with insulin glargine u100 for the management of type 1 and type 2 diabetes mellitus - from the Spanish National Health System perspective.

BACKGROUND: The objective of this study was to assess the cost-effectiveness of insulin degludec versus insulin glargine, from the Spanish NHS in three groups of patients. METHODS: A short-term cost utility model was developed to estimate effectiveness results in terms of the total number of hypoglycaemic events and their disutility impact throughout the year on the initial level of quality of life for patients in each treatment. RESULTS: Degludec was the dominant strategy for T2DM BOT and exhibited an incremental cost-effectiveness ratio of 52.70€/QALY and 11,240.88€/QALY for T1DM B/B and T2DM B/B, respectively. Lower costs are primarily driven by lower nocturnal and severe hypoglycaemic events, which were reduced versus IGlar. Improvements in clinical outcomes in all three patient groups are result of the reduced number of hypoglycaemic events showing 0.0211, 0.0328 and 0.0248 QALYs gained when compared to IGlar for T1DM B/B, T2DM BOT and T2DM B/B, respectively. Different scenario analyses showed that the ICERS were stable to plausible variations in the analysed parameters, except when the same number of SMBG for both treatments is used, with T2DM B/B showing an ICER over the accepted threshold. CONCLUSION: This analysis demonstrates that degludec is a cost-effective option in the Spanish NHS, when used in patients currently treated with long-acting insulin.

Liraglutide Versus Lixisenatide: Long-Term Cost-Effectiveness of GLP-1 Receptor Agonist Therapy for the Treatment of Type 2 Diabetes in Spain.

INTRODUCTION: Glucagon-like peptide-1 (GLP-1) receptor agonists are used successfully in the treatment of patients with type 2 diabetes as they are associated with low hypoglycemia rates, weight loss and improved glycemic control. This study compared, in the Spanish setting, the cost-effectiveness of liraglutide 1.8 mg versus lixisenatide 20 µg, both GLP-1 receptor agonists, for patients with type 2 diabetes who had not achieved glycemic control targets on metformin monotherapy. METHODS: The IMS CORE Diabetes Model was used to project clinical outcomes and costs, expressed in 2015 Euros, over patient lifetimes. Baseline cohort data and treatment effects were taken from the 26-week, open-label LIRA-LIXI™ trial (NCT01973231). Treatment and management costs of diabetes-related complications were retrieved from published sources and databases. Future benefits and costs were discounted by 3% annually. Sensitivity analyses were conducted. RESULTS: Compared with lixisenatide 20 µg, liraglutide 1.8 mg was associated with higher life expectancy (14.42 vs. 14.29 years), higher quality-adjusted life expectancy [9.40 versus 9.26 quality-adjusted life years (QALYs)] and a reduced incidence of diabetes-related complications. Higher acquisition costs resulted in higher total costs for liraglutide 1.8 mg (EUR 42,689) than for lixisenatide 20 µg (EUR 42,143), but these were partly offset by reduced costs of treating diabetes-related complications (EUR 29,613 vs. EUR 30,636). Projected clinical outcomes and costs resulted in an incremental cost-effectiveness ratio of EUR 4113 per QALY gained for liraglutide 1.8 mg versus lixisenatide 20 µg. CONCLUSIONS: Long-term projections in the Spanish setting suggest that liraglutide 1.8 mg is likely to be cost-effective compared with lixisenatide 20 µg in type 2 diabetes patients who have not achieved glycemic control targets on metformin monotherapy. Liraglutide 1.8 mg presents a clinically and economically attractive treatment option in the Spanish setting.