Cost-Utility Analysis of Biologic Therapies to Treat Chronic Plaque Psoriasis in Italy: The Importance of Using Updated and Adequate Social Tariffs to Calculate Quality-Adjusted Life-Years

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Valutazione economica dello studio CARDS: un aggiornamento

Introduction: in the last decades, prevalence and incidence of type II diabetes mellitus have been rapidly growing worldwide. Most recent projections estimate that the number of people affected by diabetes is destined to double in 2030, producing a significant increase of the healthcare expenditure for the management of complications. Prevention of cardiovascular events in diabetes population represents a priority for decision makers, who have to evaluate the cost-effectiveness of therapeutic interventions. Objective: to provide an updated cost-effectiveness evaluation of treating type II diabetes patients with atorvastatin versus placebo, in the light of the imminent price reduction of atorvastatin due to loss of exclusivity and of other therapeutic and hospital costs. Material and Methods: we derived clinical information from the CARDS study, a randomized, multicenter clinical trial evaluating efficacy of atorvastatin versus placebo in preventing the occurrence of cardiovascular events in a cohort of type II diabetes patients without previous history of coronary events. A cost-effectiveness analysis in the perspective of the National Healthcare System (SSN) has been performed, under the hypothesis of the imminent price reduction of atorvastatin, due to the loss of exclusivity. Results: after a median follow up of 3.9 years, the number of patients with at least a major cardiovascular event requiring hospitalization was lower in the atorvastatin arm (5.8%) compared to the placebo arm (9.0%; p=0.001). Based on a cohort of 1,000 patients, treatment with atorvastatin permitted to gain 29.28 life years. The incremental cost of adding atorvastatin to the standard therapy amounted to €305,682, and was partially balanced by a cost reduction due to fewer hospitalizations, compared to the placebo arm (€ 168,313). Total direct costs were of €602.186 in the atorvastatin group and of € 464,818 in the placebo group, resulting into an incremental cost-effectiveness ratio of € 4,692 for Life Year Gained (LYG). Conclusion: the present study is an update of a previous economic analysis of the CARDS trial. Under the assumed new cost scenario, the cost-effectiveness profile of treating diabetic patients with atorvastatin becomes highly favourable, and leads to a significant reduction of the cost for Life Year Gained compared to the previous findings

Status of correlation between BMI and response to immunocheck-point inhibitor in advanced non-small-cell lung cancer

Recently, clinical evidence has raised BMI as an emerging prognostic factor for immunotherapy, regardless of cancer types. In this article we rewirw current data about correlation between BMI and response to immunocheck-point inhibitor in advanced non-small-cell lung cance

Cost-Effectiveness Analysis of Dimethyl Fumarate in the Treatment of Relapsing Remitting Multiple Sclerosis: An Italian Societal Perspective

BACKGROUND: Delayed-release dimethyl fumarate (also known as gastro-resistant dimethyl fumarate, hereafter dimethyl fumarate) is an oral disease-modifying therapy used for the treatment of Relapsing-Remitting Multiple Sclerosis (RRMS), an autoimmune chronic inflammatory condition of the central nervous system.OBJECTIVE: The objective of this economic analysis was to compare cost-effectiveness of dimethyl fumarate with the alternatives used as first-line treatment of RRMS in Italy.METHODS: The analysis was conducted from the Italian societal perspective. Health outcomes and costs were evaluated over a 50-year time horizon (equivalent to a lifetime horizon). Both health outcomes and costs were discounted at 3.5%. The cost-effectiveness analysis was conducted by adapting a Markov model, already used in previous similar economic analyses conducted in RRMS, to the Italian context. The Markov model estimated the clinical and economic consequences of treating RRMS patients with the following therapeutic options: dimethyl fumarate; interferon (IFN) beta-1a subcutaneous (SC) at two different doses, 22 mcg and 44 mcg; IFN beta-1b SC; glatiramer acetate (GA) SC 20 mg; oral teriflunomide. Clinical efficacy data were retrieved from an elaboration of an already published mixed treatment comparison (MTC). Both direct and indirect costs (disability, treatment acquisition, administration, monitoring, relapses, adverse events) were included in the analysis. One-way and probabilistic sensitivity analyses were carried out and cost-effectiveness acceptability curves generated.RESULTS: In the base-case analysis, dimethyl fumarate was more efficacious than alternatives, in terms of both survival (19.634 vs. 19.440-19.600 life years for alternatives), and quality-of-life-adjusted survival (6.526 vs. 5.143- 6.189 QALYs for alternatives). The total lifetime cost per patient treated with dimethyl fumarate (€ 954,286) was lower than that of the other DMTs included in the analysis. Therefore, dimethyl fumarate was dominant compared with all analyzed alternatives. Dimethyl fumarate was also the therapeutic option with the highest benefit on disease burden. In fact, costs of disability management were lower than those of all the other first-line drugs included in the analysis. The results of one-way deterministic sensitivity analysis and probabilistic sensitivity analysis confirmed the reliability of base-case results.CONCLUSIONS: The results of the cost-effectiveness analysis confirm that dimethyl fumarate is an optimal first-line treatment for RRMS in Italy, compared with the other first-line alternatives included in the economic analysis, when evaluated from the societal perspective

Critical Review of the Pivotal Studies of Four rFVIII Products for the Treatment of Hemophilia A Patients: The Role of Octocog Alfa

INTRODUCTION: Hemophilia A is a rare congenital bleeding disorder caused by a deficiency of clotting factor VIII (FVIII). The severe form of the disease is characterized by spontaneous bleeds, especially into the joints. Prophylaxis, based on regularly intravenous administration of the missing factor to avoid hemorrhages, represents the gold standard of treatment. In recent years, new products that significantly improve the treatment management options for patients with hemophilia have become available in the market.OBJECTIVE: To critically evaluate the pivotal studies of recombinant FVIII (rFVIII) products, approved in Europe within the first half of 2018 having obtained the indication for a prophylaxis dosing regimen based also on a twice weekly infusion frequency or even less, highlighting their limitations or strengths.METHODS: A systematic literature search was conducted, and several databases (PubMed and Embase) were consulted.RESULTS: Nine clinical trials involving patients with severe hemophilia A without inhibitor were included in this analysis. Four rFVIII products (Elocta®, Biogen, Cambridge, MA, USA; Kovaltry®, Bayer HealthCare Pharmaceuticals, Germany; Afstyla®, CSL Behring GmbH, Germany; Adynovi®, Baxalta Innovation GmbH, Austria) with different pharmacokinetic profiles were evaluated. The trials included in this analysis had different designs and heterogeneous methods were utilized to assess the study outcomes. The baseline characteristics of the patients enrolled in the studies were also often different and sometimes not adequately described. LEOPOLD II, a trial to compare prophylaxis to on-demand therapy with an unmodified rFVIII product (Kovaltry®, octocog alfa), was the only completely randomized trial that enrolled a more critical patient population in terms of compromised joint condition than the other studies. Based on these side-by-side comparison, Octocog alfa reported similar efficacy, in terms of annualized bleeding rate, to the other rFVIII products, including extended half-life.CONCLUSIONS: Even without structural modifications, octocog alfa may be considered a useful treatment option for two times a week prophylaxis in a selected population of haemophilia patients

The Value and Sustainability of Ocrelizumab in Relapsing Multiple Sclerosis: A Cost-Effectiveness and Budget Impact Analysis

INTRODUCTION: The availability of ocrelizumab for the relapsing forms of multiple sclerosis (MS) in the Italian markets raised some questions about its economic impact and value compared to the alternative treatment options available.AIM: To assess the cost-effectiveness and budget impact of ocrelizumab compared to the most used second line disease modifying therapies (DMTs) in Italy.METHODS: The study was divided in two phases: Phase 1 – based on the development of a decision analytical Markov model to assess the cost-effectiveness of ocrelizumab compared to natalizumab and fingolimod, and Phase 2 – based on the development of a budget impact model to assess the economic impact of ocrelizumab in Italy. Both models used the National Health System perspective; a lifetime horizon was applied in the cost-effectiveness analysis and a 3-year time horizon in the budget impact. The cost-effectiveness analysis results were reported as incremental cost-effectiveness ratio (ICER) expressed as € per Quality Adjusted Life Year (QALY) gained, the budget impact analysis results were reported as difference in the overall budget (€) between a scenario with and without ocrelizumab.RESULTS: The two analyses reported ocrelizumab as a cost-effective option compared to natalizumab and fingolimod with a positive impact on the overall NHS budget. In the base-case analysis, the ICER was € 2,023 for ocrelizumab compared to fingolimod; while ocrelizumab resulted cost-saving compared to natalizumab. The sensitivity analysis confirmed the base-case analysis results. Further, the use of ocrelizumab was associated to a budget decrease of € 21 million (-2.6%) in a 3-year time horizon.CONCLUSION: The results of our cost-effectiveness and budget impact models reported ocrelizumab as an effective and efficient treatment in patients with relapsing forms of MS who failed a first line DMTs from the Italian NHS perspective

Niosomes for Topical Application of Antioxidant Molecules: Design and In Vitro Behavior

In the present study, gels based on xanthan gum and poloxamer 407 have been developed and characterized in order to convey natural antioxidant molecules included in niosomes. Specifically, the studies were conducted to evaluate how the vesicular systems affect the release of the active ingredient and which formulation is most suitable for cutaneous application. Niosomes, composed of Span 20 or Tween 20, were produced through the direct hydration method, and therefore, borate buffer or a micellar solution of poloxamer 188 was used as the aqueous phase. The niosomes were firstly characterized in terms of morphology, dimensional and encapsulation stability. Afterwards, gels based on poloxamer 407 or xanthan gum were compared in terms of spreadability and adhesiveness. It was found to have greater spreadability for gels based on poloxamer 407 and 100% adhesiveness for those based on xanthan gum. The in vitro diffusion of drugs studied using Franz cells associated with membranes of mixed cellulose esters showed that the use of a poloxamer micellar hydration phase determined a lower release as well as the use of Span 20. The thickened niosomes ensured controlled diffusion of the antioxidant molecules. Lastly, the in vivo irritation test confirmed the safeness of niosomal gels after cutaneous application

Spinal Fusion Surgery: Epidemiologic and Economic Burden Attributable to First Intervention

IntroductionLow back pain (LBP) is the single most common cause for disability in individuals aged 50 years or younger with a high socioeconomic impact. In USA, LBP costs are estimated to exceed $1..

Ellagic acid containing Nanostructured Lipid Carriers for topical application: a preliminary study

Ellagic acid (EA) is a potent antioxidant substance of natural origin characterized by poor biopharmaceutical properties and low solubility in water that limit their use. The aim of the present study was to develop lipid based nanoparticle formulations able to encapsulate EA for dermal delivery purpose. The EA-loaded nanoparticles were prepared using two different lipid compositions, namely tristearin/tricaprylin (NLC-EA1) and tristearin/labrasol (NLC-EA2). The influence of formulations on size, entrapment efficiency and stability of EA-loaded nanoparticles was investigated. Cryo-TEM and SAXS analysess showed that no morphological differences are evident among all the types of loaded and unloaded NLC. The macroscopic aspect of both NLC-EA1 and NLC-EA2 did not change by time. No difference in size is appreciable between empty and drug-containing NLC, thus the nanoparticle diameter is not affected by the presence EA and in general no variations of the diameters occur during time. The percentage of entrapment efficiency of both EA-loaded nanoparticles was almost quantitative. In addition NLC-EA1 maintain EA stability for almost 2 months, while NLC-EA2 up to 40 days. FRAP assay showed an antioxidant activity around 60% for both the loaded NLC, as compared to the solution. Although both types of NLC are characterized by some toxicity, NLC-EA1 are less cytotoxic than NLC-EA2. Taken together these results demonstrated that the inclusion of EA within NLC could improve the water solubility, allowing for a reduction of the dosage. Moreover, the maintaining of high antioxidant effect and low toxicity were evidenced for both types of NLC-EA