Economic evaluation of apixaban for the prevention of stroke in non-valvular atrial fibrillation in the Netherlands.

BACKGROUND: Stroke prevention is the main goal of treating patients with atrial fibrillation (AF). Vitamin-K antagonists (VKAs) present an effective treatment in stroke prevention, however, the risk of bleeding and the requirement for regular coagulation monitoring are limiting their use. Apixaban is a novel oral anticoagulant associated with significantly lower hazard rates for stroke, major bleedings and treatment discontinuations, compared to VKAs. OBJECTIVE: To estimate the cost-effectiveness of apixaban compared to VKAs in non-valvular AF patients in the Netherlands. METHODS: Previously published lifetime Markov model using efficacy data from the ARISTOTLE and the AVERROES trial was modified to reflect the use of oral anticoagulants in the Netherlands. Dutch specific costs, baseline population stroke risk and coagulation monitoring levels were incorporated. Univariate, probabilistic sensitivity and scenario analyses on the impact of different coagulation monitoring levels were performed on the incremental cost-effectiveness ratio (ICER). RESULTS: Treatment with apixaban compared to VKAs resulted in an ICER of €10,576 per quality adjusted life year (QALY). Those findings correspond with lower number of strokes and bleedings associated with the use of apixaban compared to VKAs. Univariate sensitivity analyses revealed model sensitivity to the absolute stroke risk with apixaban and treatment discontinuations risks with apixaban and VKAs. The probability that apixaban is cost-effective at a willingness-to-pay threshold of €20,000/QALY was 68%. Results of the scenario analyses on the impact of different coagulation monitoring levels were quite robust. CONCLUSIONS: In patients with non-valvular AF, apixaban is likely to be a cost-effective alternative to VKAs in the Netherlands.

Cost-effectiveness of rituximab as maintenance treatment for relapsed follicular lymphoma: results of a population-based study.

OBJECTIVES: On the basis of two population-based registries, our study aims to calculate the real-world cost-effectiveness of rituximab maintenance compared with observation in relapsed or refractory follicular lymphoma patients who responded to second-line chemotherapy. METHODS: Data were obtained from the EORTC20981 trial, the Netherlands Cancer Registry and two population-based registries. A Markov model was developed to calculate cost per life year gained (LYG) and quality-adjusted life years (QALYs) for three scenarios. RESULTS: Our real-world patients were (62 years) 6 to 7 years older and had higher complete response rates to second-line chemotherapy than the trial population. Differences between the real-world rituximab and observation group were observed for second-line chemotherapy and disease progression. Groups were more balanced after using propensity matching. Relying entirely on updated trial results (scenario1) in combination with local cost data resulted in ratios of €11,259 per LYG and €12,655 per QALY. For scenario2, consisting of trial efficacy and matched real-world costs, ratios of €21,202 per LYG and €23,821 per QALY were calculated. Using real-world matched evidence (scenario3) for both effectiveness and costs showed ratios of €10,591 per LYG and €11,245 per QALY. CONCLUSION: Although differences in real-world and trial population were found, using real-world data as well as results from long-term trial follow-up showed favourable ICERs for rituximab maintenance. Nevertheless, results showed that caution is required with data synthesis, interpretation and generalisability of results. As different scenarios provide answers to different questions, we recommend healthcare decision-makers to recognise the importance of calculating several cost-effectiveness scenarios.

Cost effectiveness of adding dapagliflozin to insulin for the treatment of type 2 diabetes mellitus in the Netherlands.

BACKGROUND AND OBJECTIVE: Many patients with type 2 diabetes mellitus (T2DM) on insulin therapy have inadequate glycaemic control. In such cases, Dutch guidelines recommend unlimited up-titration of insulin, yet in practice many patients never reach their glycaemic target. Clinical evidence shows that dapagliflozin-a highly selective sodium-glucose cotransporter 2 inhibitor-meets a need for these patients, i.e. by reducing glycated haemoglobin levels and bodyweight. We estimated the cost effectiveness and cost utility of adding dapagliflozin to insulin compared with not adding dapagliflozin in patients with T2DM who have inadequate glycaemic control while on insulin. METHODS: The cost effectiveness of dapagliflozin was estimated using the Cardiff Diabetes Model, using direct comparative efficacy data from a randomized placebo-controlled trial (ClinicalTrials.gov identifier NCT00673231). In this trial, up-titration of insulin was allowed in case of severe glycaemic imbalance. Risk factor progression and the occurrence of future vascular events were estimated using the United Kingdom Prospective Diabetes Study 68 risk equations. Costs and utilities were derived from the literature. The analysis was conducted from the societal perspective, simulating the remaining lifetime of the patients. RESULTS: The overall incidence of macro- and microvascular complications was lower, and life expectancy was greater (19.43 versus 19.35 life-years [LYs]) in patients receiving dapagliflozin than in those not receiving dapagliflozin. Patients in the dapagliflozin arm obtained an incremental benefit of 0.42 quality-adjusted life-years (QALYs). The lifetime incremental cost per patient in the dapagliflozin arm was €2,293, resulting in an incremental cost-effectiveness ratio of €27,779 per LY gained and an incremental cost-utility ratio of €5,502 per QALY gained. Sensitivity and scenario analyses showed that the results were insensitive to variations in modelling assumptions and input variables. CONCLUSION: Dapagliflozin in combination with insulin was estimated to be a cost-effective treatment option for patients with T2DM whose insulin treatment regimen does not provide adequate glycaemic control in a Dutch healthcare setting.

Transferability of model-based economic evaluations: the case of trastuzumab for the adjuvant treatment of HER2-positive early breast cancer in the Netherlands.

INTRODUCTION: Geographic transferability of model-based cost-effectiveness results may facilitate and shorten the reimbursement process of new pharmaceuticals. This study provides a real world example of transferring a cost-effectiveness study of trastuzumab for the adjuvant treatment of HER2-positive early breast cancer from the United Kingdom to The Netherlands. METHODS: Three successive steps were taken. Step 1: Collect available information with regard to the original model, and assess transferability using existing checklists. Step 2: Adapt transferability-limiting factors. Step 3: Obtain a country-specific estimate of cost-effectiveness. RESULTS: The structure of the UK model was transferable, although some of the model inputs needed adaptation. From a health-care perspective, the Dutch estimate amounted to euro5828/quality-adjusted life-year gained. From a societal perspective, the incremental cost-effectiveness ratio was dominant. CONCLUSION: Transferability of a model-based UK-study in three steps proved to be an efficient method to provide an early indication of the cost-effectiveness of trastuzumab and has led to the provisional reimbursement of the treatment.

Direct costs associated with the disease management of patients with unresectable advanced non-small-cell lung cancer in The Netherlands.

INTRODUCTION: Disease management and costs of treatment of patients with unresectable advanced non-small-cell lung cancer (NSCLC) in The Netherlands are not well known. METHODS: A retrospective medical chart review was performed by collecting data from the time of diagnosis until the time of death or the end of the evaluation period. In addition to the demographic data, information was collected on the overall management of the patient. Hospital resource utilisation data collected included number of outpatient specialist visits, number and length of hospitalisation, type and number of diagnostic and laboratory procedures, type and number of radiotherapy cycles and detailed information on chemotherapy. To evaluate the economic impact of second-line treatment, a distinction was made between patients who received only best supportive care (BSC, group A) and those who received chemotherapy as a second-line treatment in addition to BSC (group B). The study was performed from the hospital perspective and reports on 2005 costs. RESULTS: Of 102 patients, 74 belonged to group A and 28 to group B. Patient management included a multidisciplinary approach, the extent of which depended on symptoms of the disease and presence of metastases. The average total treatment cost per patient per year of unresectable advanced NSCLC in The Netherlands was euro32,840 in group A and euro31,187 in group B. In both groups, hospitalisation was the major cost driver. In group B second-line chemotherapy was the second largest contributor of the costs. In spite of the difference in numbers of treatment lines provided to patients in groups A and B the total average costs per patient per year were comparable. Overall, the management of unresectable advanced NSCLC appeared to conform with current guidelines in The Netherlands. CONCLUSION: These patients show high medical resource consumption, with hospitalisation being the main cost driver in both groups. As economic arguments are becoming increasingly important in medical decision making on both national and local levels, this information is relevant for both policy makers and specialists. These data can also be used in future research to evaluate the economic impact of new therapies in NSCLC, especially of those that aim to treat patients in an outpatient setting.

Healthcare utilization, quality of life and patient-reported outcomes during two years of GH replacement therapy in GH-deficient adults--comparison between Sweden, The Netherlands and Germany.

OBJECTIVE: This study set out to determine the change in quality of life (QoL) and healthcare utilization during 2 years of growth hormone (GH) replacement therapy in adults with GH deficiency. Data were compared from three European countries. DESIGN: Analysis was made from KIMS, the Pfizer International Metabolic Database on adult GH deficiency. METHODS: QoL and healthcare utilization were measured at baseline and after 1 and 2 years of GH replacement in patient cohorts from Sweden (n = 302), The Netherlands (n = 103) and Germany (n = 98). QoL was assessed by the QoL-Assessment in Growth Hormone Deficient Adults (QoL-AGHDA) questionnaire, and the KIMS Patient Life Situation Form was used to evaluate healthcare utilization. RESULTS: QoL improved significantly (P < 0.0001) and comparably in all three cohorts. The improvement was seen during the first year of treatment and QoL remained improved during the second year. The number of days in hospital was reduced by 83% (P < 0.0001) during GH replacement. There were no country-specific differences either at baseline or during follow-up. The same was true for the number of days of sick leave (reduction of 63%; P = 0.0004). Significant reductions were recorded in the number of doctor visits in each of the three cohorts after 2 years of GH replacement (P < 0.05). CONCLUSIONS: This study provides a detailed comparative analysis of GH replacement therapy in GHD patients in three European countries. Despite some differences in treatment strategies, the beneficial effects on QoL, patient-reported outcomes and healthcare utilization are essentially similar in the healthcare environment of Western European countries.

Products from human mast cell line cells enhance the production of interferon-gamma by CD8+ and CD4+ T cells.

In patients with allergic asthma, T-cell cytokines are implicated in the regulation of the local inflammation in the airways. The ability of sensitized mast cells to release mediators and cytokines early upon allergen stimulation makes them important candidates for local immunoregulation. We have studied the effects of human mast cells on T cells with the use of the human mast cell line HMC-1. We showed that activated human mast cells or their soluble products induced and enhanced the interferon-gamma (IFN-gamma) production by T cells up to about 60-fold. The production of interleukin (IL)-4 was hardly affected and that of IL-5 was slightly enhanced. The enhancement of IFN-gamma production was induced both in polyclonal CD4+ and CD8+ T cells and in CD4+ and CD8+ T-cell clones. Further characterization of the factors involved demonstrated a molecular mass above 30 000. Our results implicate that by this mechanism mast cells may account for a negative feedback system locally down-regulating allergen-induced T helper 2 responses via IFN-gamma production by the T cells.