Posaconazole vs fluconazole/itraconazole in the prophylaxis of invasive fungal infections in immunocompromised patients: A cost-effectiveness analysis in Greece

Abstract

Background:

Invasive fungal infections (IFIs) present a major issue in clinical practice, due to their high morbidity and mortality rates. In a pivotal multi-centre, randomized clinical trial, posaconazole prophylaxis prevented IFIs more effectively than did either fluconazole or itraconazole, and improved overall survival.

Objective:

The aim of this study was to perform an economic evaluation of the aforementioned therapeutic strategies for IFI prophylaxis in neutropenic patients, in the Greek healthcare setting.

Method:

A decision analytic model was developed, which described the course of neutropenic patients under posaconazole or standard azole (fluconazole or itraconazole) treatment. Effectiveness data for each treatment regimen were derived from published results of a pivotal, multi-centre, randomized clinical trial. Cost and healthcare resources utilization data depict Greek clinical practice and are derived from official Greek sources, from a third party payer perspective.

Results:

Prophylaxis with posaconazole resulted in fewer IFIs (0.05 vs 0.11 per patient) compared to treatment with fluconazole or itraconazole, during the first 100 days from initiation of prophylaxis treatment. The cost per avoided IFI with posaconazole was €6455, while the incremental cost per life year gained (LYG) was estimated at €24,196. Extensive sensitivity analyses corroborated the base-case results. Possible limitations of the study are the exclusion of indirect and outpatient costs from the analysis and the inherent uncertainty with regards to the transferability of the clinical efficacy results of the clinical trial to the Greek healthcare setting.

Conclusions:

The utilization of posaconazole for prophylaxis of IFIs neutropenic patients is a therapeutic strategy that provides superior clinical efficacy, while being cost-effective compared to alternative therapies.     

Cost-effectiveness of primary antifungal prophylaxis with posaconazole versus itraconazole in allogeneic hematopoietic stem cell transplantation

Abstract

Purpose:

To evaluate the cost-effectiveness of posaconazole vs itraconazole in the prevention of invasive fungal infections (IFIs) in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods:

Total hospital-based costs from initial admission for allo-HSCT until day 100 after transplantation were evaluated for 49 patients in whom the clinical efficacy of antifungal prophylaxis with posaconazole vs itraconazole had been previously analyzed and reported. Clinical and economic data were used to determine the incremental costs per IFI avoided and per life-year gained for posaconazole compared with itraconazole. Confidence intervals for the incremental cost-effectiveness ratio (ICER) and a cost-effectiveness acceptability curve were estimated through bootstrapping with the bias-corrected percentile method.

Results:

According to our analysis, the total cost of allo-HSCT per patient during the 100-day fixed-treatment period was €46,562 in the posaconazole group (n?=?33) and €45,080 in the itraconazole group (n?=?16). However, the reduction in the incidence of IFI and the improved outcome with posaconazole resulted in a favorable ICER of €11,856 per IFI avoided and €5218 per life-year gained. With the outcomes of the bootstrap procedure, the cost-effectiveness acceptability curve was constructed. Assuming a threshold of €30,000 per life-year gained, the ICER based on life-years gained is acceptable with 75% certainty.

Limitations:

This evaluation is based on data from a single-center, non-randomized study. Preference weights or utilities were not available to calculate quality-adjusted life-years. Extra-mural costs were only partially evaluated from a hospital perspective. Indirect costs and economic consequences are not included.

Conclusions:

This economic evaluation compared direct medical costs associated with posaconazole or itraconazole treatment; the data suggest that posaconazole may be cost-effective as antifungal prophylaxis during the early high-risk neutropenic period and up to 100 days after allo-HSCT.     

Adapting a global cost-effectiveness model to local country requirements: posaconazole case study

Abstract

Background:

Many countries have various requirements for local economic analyses to assess the value of a new health technology and/or to secure reimbursement. This study presents a case study of an economic model developed to assess the cost-effectiveness of posaconazole vs standard azole therapy (fluconazole/itraconazole) to prevent invasive fungal infections (IFIs), which was adapted by at least 11 countries.

Methods:

Modeling techniques were used to assess the cost-effectiveness of posaconazole vs fluconazole/itraconazole as IFI prophylaxis in patients with acute myelogenous leukemia or myelodysplastic syndromes and chemotherapy-induced neutropenia. For the core model, the probabilities of experiencing an IFI, IFI-related death, and death from other causes were estimated from clinical trial data. Long-term mortality, drug costs, and IFI treatment costs were obtained from secondary sources. Locally changed parameters were probabilities of long-term death and survival, currency, drug costs, health utility, IFI treatment costs, and discount rate.

Results:

Locally adapted cost-effective modeling studies indicate that prophylaxis with posaconazole, compared with fluconazole/itraconazole, prolongs survival, and, in most countries, is cost-saving. In all countries, the model predicted that prophylaxis with posaconazole would be associated with an increase in life-years, with increases ranging from 0.016–0.1 life-year saved. In all countries, use of the model led to posaconazole being approved by the appropriate reimbursement authority.

Limitations:

The study did not have power to detect differences between posaconazole and fluconazole or itraconazole separately. The risk of death after 100 days was assumed to be equal for those who did and did not develop an IFI, and equal probabilities of IFI-related and other death during the trial period were used for both groups.

Conclusions:

A core economic model was successfully adapted locally by several countries. The model showed that posaconazole was cost-saving or cost-effective vs fluconazole/itraconazole and led to positive reimbursement listings.     

Cost effectiveness of zoledronic acid in the management of skeletal metastases in hormone-refractory prostate cancer patients in France,Germany, Portugal,and the Netherlands

Abstract

Objective:

Zoledronic acid (ZOL) reduces the risk of skeletal related events (SREs) in hormone-refractory prostate cancer (HRPC) patients with bone metastases. This study assessed the cost effectiveness of ZOL for SRE management in French, German, Portuguese, and Dutch HRPC patients.

Methods:

This analysis was based on the results of a randomized phase III clinical trial wherein HRPC patients received up to 15 months of ZOL (n?=?214) or placebo (n?=?208). Clinical inputs were obtained from the trial. Costs were estimated using hospital tariffs, published, and internet sources. Quality adjusted life-years (QALYs) gained were estimated from a separate analysis of EQ-5D scores reported in the trial. Uncertainty surrounding outcomes was addressed via univariate sensitivity analyses.

Results:

ZOL patients experienced an estimated 0.759 fewer SREs and gained an estimated 0.03566 QALYs versus placebo patients. ZOL was associated with reduced SRE-related costs [net costs] (?€2396 [€1284] in France, ?€2606 [€841] in Germany, ?€3326 [€309] in Portugal and ?€3617 [€87] in the Netherlands). Costs per QALY ranged from €2430 (Netherlands) to €36,007 (France).

Conclusions:

This analysis is subject to the limitations of most cost-effectiveness analyses: it combines data from multiple sources. Nevertheless, the results strongly suggest that ZOL is cost effective versus placebo in French, German, Portuguese, and Dutch HRPC patients.     

Comparison of treatment costs in inadequately controlled type 2 diabetes in Germany based on the APOLLO trial with insulin glargine

Abstract

Objective: A cost analysis of once-daily insulin glargine versus three-times daily insulin lispro in combination with oral antidiabetic drugs (OADs) for insulin-naive type 2 diabetes patients in Germany based on the APOLLO trial (A Parallel design comparing an Oral antidiabetic drug combination therapy with either Lantus once daily or Lispro at mealtime in type 2 diabetes patients failing Oral treatment).

Methods: Annual direct treatment costs were estimated from the perspective of the German statutory health insurance (SHI). Costs accounted for included insulin medication, disposable pens and consumable items (needles, blood glucose test strips and lancets). Sensitivity analyses (on resource use and unit costs) were performed to reflect current German practice.

Results: Average treatment costs per patient per year in the base case were €1,073 for glargine and €1,794 for lispro. Insulin costs represented 65% vs. 37% of total costs respectively. Acquisition costs of glargine were offset by the lower costs of consumable items (€380 vs. €1,139). Sensitivity analyses confirmed the robustness of the results in favour of glargine. All scenarios yielded cost savings in total treatment costs ranging from €84 to €727.

Conclusions: Combination therapy of once-daily insulin glargine versus three-times daily insulin lispro both with OADs, in the management of insulin-dependent type 2 diabetes offers the potential for substantial cost savings from the German SHI perspective.     

Inverse probability weighting to control for censoring in a post hoc analysis of quality-adjusted survival data from a clinical trial of temsirolimus for renal cell carcinoma

Abstract

Objectives: The Belgian third-party payer wishes to set reimbursement tariffs at a level that reflects the costs of orthotic braces. This article aims to calculate production and distribution costs of a prefabricated hard neck and knee brace and to explore whether Belgian tariffs and actual retail prices correspond with estimated costs of these two braces.

Methods: The cost model considered manufacturing costs, general overheads, research and development costs, warehousing costs, profit and distribution margins. Data were gathered from manufacturers, a production site visit, desk research, a decomposition of finished products and stakeholder interviews. The price year was 2007.

Results: The cost model estimated a retail price of €55–€150 for the neck brace, depending on assumptions. The estimated retail price for the neck brace was lower than the reimbursement tariff of €194 and the actual retail price of €241. The estimated retail price of €331–€694 for the knee brace was lower than the actual retail price of €948.

Conclusions: Actual retail prices and reimbursement tariffs for a neck brace and a knee brace exceeded prices based on estimated costs. Therefore, there appears to be scope for reducing tariffs.     

Comparative cost analysis of management of secondary hyperparathyroidism with paricalcitol or cinacalcet with low-dose vitamin D in hemodialysis patients

Abstract

Objective:

The objective of this analysis was to compare costs of paricalcitol or cinacalcet plus low dose vitamin D, and of phosphate binders, in patients in the IMPACT SHPT study; and to extrapolate those to estimate expected annual maintenance costs.

Methods:

IMPACT SHPT was a 28-week, randomized, open-label trial. Subjects from 12 countries received intravenous (IV) or oral paricalcitol, or oral cinacalcet plus fixed IV doxercalciferol or oral alfacalcidol. The primary end-point was the proportion of subjects who achieved a mean intact parathyroid hormone (iPTH) value of 150–300?pg/mL during weeks 21–28 (evaluation period). This study compares the costs of study drugs and phosphate binders among participants during the study and annualized. This analysis includes only those subjects that reached the evaluation period (134 in each group).

Results:

The mean total drug costs over the study period were €2606 (SD?=?€2000) in the paricalcitol group and €3034 (SD?=?€3006) in the cinacalcet group (difference €428, p?=?0.1712). The estimated annualized costs were €5387 (SD?=?€4139) in the paricalcitol group and €6870 (SD?=?€6256) in the cinacalcet group (difference €1492, p?=?0.0395). In addition, a significantly greater proportion (p?=?0.010) of subjects in the paricalcitol arm (56.0%) achieved an iPTH of 150–300?pg/mL during the evaluation period compared to the cinacalcet arm (38.2%).

Limitations:

This was a secondary analysis of the IMPACT SHPT study which was not designed or powered for costs as an outcome. The dosing of study drugs and phosphate binders in the IMPACT study may not reflect actual practice, and patients were followed for 28 weeks, while the treatment of SHPT is long-term.

Conclusion:

Patients with SHPT requiring hemodialysis who were treated with a paricalcitol-based regimen for iPTH control had lower estimated annual drug costs compared to those treated with cinacalcet plus low-dose vitamin D.     

Economic evaluation of dabigatran etexilate for the primary prevention of venous tromboembolic events following major orthopedic surgery in the Netherlands

Abstract

Objectives:

Dabigatran etexilate is a new oral direct thrombin inhibitor for prophylaxis of venous thromboembolism (VTE) in patients who have elective surgery for total hip replacement (THR) or total knee replacement (TKR). Among the advantages of dabigatran etexilate over subcutaneous prophylaxis with Low Molecular Weight Heparin (LMWH) are reduced resource uses for (i) teaching patients to self-inject; (ii) home-care visits for subcutaneous administration; and (iii) absence of heparin-induced thrombocytopenia (HIT). Based on the demonstrated non-inferiority, the aim of this study was to conduct a cost-minimization analysis of oral dabigatran etexilate vs subcutaneous low-molecular weight heparin (LMWH) and fondaparinux from the Dutch healthcare perspective.

Methods:

A retrospective cohort study was conducted to measure resource use associated with subcutaneous prophylaxis. Results of this study were used in the model to elucidate specific advantages of dabigatran etexilate, next to reduced needs for self-inject teaching and lack of Heparin-Induced Thrombocytopenia. Drug and other resource utilization data were combined with local unit costs. Probabilistic sensitivity analysis was performed to account for uncertainty around relevant parameters included.

Results:

Home-care visits for subcutaneous administration problems were needed in 9.9% (95% CI?=?6.4–13.4) and 9.6% (95% CI?=?5.8–13.4) of THR and TKR patients, respectively. Based on costs for 1000 patients treated with dabigatran etexilate vs LMWHs, per patient cost-savings with dabigatran etexilate were estimated at €30.68 (95% CI?=?2.01–65.52) and €23.19 (95% CI?=?0.69–48.48) for THR and TKR, respectively. The probability that dabigatran etexilate would be cost-saving was estimated at 98.3% and 97.9% for THR and TKR, respectively. These cost-savings were even higher when including fondaparinux in the analysis, with per patient cost-savings of €69.87 (43.42–106.10) and €18.33 (1.63–41.26) for THR and TKR, respectively. Separate calculations for dabigatran etexilate vs nadroparin and dalteparin in THR resulted in probabilities of achieving cost-savings with dabigatran etexilate of 36.2% and 100%, respectively. For TKR these probabilities were estimated at 54.3% and 100%, respectively.

Conclusions:

Thromboprophylaxis with dabigatran etexilate is cost-saving in patients undergoing THR and TKR from the Dutch healthcare perspective, compared to subcutaneous LMWHs.     

Cost effectiveness analysis of immunotherapy in patients with grass pollen allergic rhinoconjunctivitis in Germany

Abstract

Objectives:

An economic evaluation was conducted to assess the outcomes and costs as well as cost-effectiveness of the following grass-pollen immunotherapies: OA (Oralair; Stallergenes S.A., Antony, France) vs GRZ (Grazax; ALK-Abelló, Hørsholm, Denmark), and ALD (Alk Depot SQ; ALK-Abelló) (immunotherapy agents alongside symptomatic medication) and symptomatic treatment alone for grass pollen allergic rhinoconjunctivitis.

Methods:

The costs and outcomes of 3-year treatment were assessed for a period of 9 years using a Markov model. Treatment efficacy was estimated using an indirect comparison of available clinical trials with placebo as a common comparator. Estimates for immunotherapy discontinuation, occurrence of asthma, health state utilities, drug costs, resource use, and healthcare costs were derived from published sources. The analysis was conducted from the insurant’s perspective including public and private health insurance payments and co-payments by insurants. Outcomes were reported as quality-adjusted life years (QALYs) and symptom-free days. The uncertainty around incremental model results was tested by means of extensive deterministic univariate and probabilistic multivariate sensitivity analyses.

Results:

In the base case analysis the model predicted a cost-utility ratio of OA vs symptomatic treatment of €14,728 per QALY; incremental costs were €1356 (95%CI: €1230; €1484) and incremental QALYs 0.092 (95%CI: 0.052; 0.140). OA was the dominant strategy compared to GRZ and ALD, with estimated incremental costs of ?€1142 (95%CI: ?€1255; ?€1038) and ?€54 (95%CI: ?€188; €85) and incremental QALYs of 0.015 (95%CI: ?0.025; 0.056) and 0.027 (95%CI: ?0.022; 0.075), respectively. At a willingness-to-pay threshold of €20,000, the probability of OA being the most cost-effective treatment was predicted to be 79%. Univariate sensitivity analyses show that incremental outcomes were moderately sensitive to changes in efficacy estimates. The main study limitation was the requirement of an indirect comparison involving several steps to assess relative treatment effects.

Conclusion:

The analysis suggests OA to be cost-effective compared to GRZ and ALD, and a symptomatic treatment. Sensitivity analyses showed that uncertainty surrounding treatment efficacy estimates affected the model outcomes.     

Cost-effectiveness of dabigatran etexilate in the prevention of stroke and systemic embolism in patients with atrial fibrillation in Belgium

Abstract

Objective:

To assess the cost-effectiveness of dabigatran etexilate (‘dabigatran’) vs vitamin K antagonists (VKAs) in the Belgian healthcare setting for the prevention of stroke and systemic embolism (SE) in patients with non-valvular atrial fibrillation (AF).

Research design and methods:

A Markov model was used to calculate the cost-effectiveness of dabigatran vs VKAs in Belgium, whereby warfarin was considered representative for the VKA class. Efficacy and safety data were taken from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial and a network meta-analysis. Local resource use and unit costs were included in the model. Effectiveness was expressed in Quality Adjusted Life-Years (QALYs). The model outcomes were total costs, total QALYs, incremental costs, incremental QALYs and the incremental cost-effectiveness ratio (ICER). The level of International Normalized Ratio (INR) control and the use of other antithrombotic therapies observed in Belgian clinical practice were reflected in two scenario analyses.

Results:

In the base case analysis, total costs per patient were €13,333 for dabigatran and €12,454 for warfarin. Total QALYs per patient were 9.51 for dabigatran and 9.19 for warfarin. The corresponding ICER was €2807/QALY. The ICER of dabigatran was €970/QALY vs warfarin with real-world INR control and €5296/QALY vs a mix of warfarin, aspirin, and no treatment. Results were shown to be robust in one-way and probabilistic sensitivity analyses.

Limitations:

The analysis does not include long-term costs for clinical events, as these data were not available for Belgium. As in any economic model based on data from a randomized clinical trial, several assumptions had to be made when extrapolating results to routine clinical practice in Belgium.

Conclusion:

This analysis suggests that dabigatran, a novel oral anticoagulant, is a cost-effective treatment for the prevention of stroke and SE in patients with non-valvular AF in the Belgian healthcare setting.     

Modelling the lifetime economic consequences of glaucoma in France

Abstract

Objective: To estimate the lifetime economic consequences of glaucoma in France.

Methods: A Markov model estimated the average discounted outcome and cost of glaucoma treatment over a patient's lifetime. Clinical states were defined as first- to fourth-line drugs, no treatment, laser therapy, surgery, blindness and death. After each failure (always after the fourth-line drug) patients could receive either laser treatment or surgery followed by no treatment, or a new treatment. A societal perspective was adopted. Sensitivity analyses were performed.

Results: Discounted medical costs were €7,322 for ocular hypertension treatment (OHT) and €8,488 for a glaucoma patient. Social costs of OHT and glaucoma patients exceeded medical costs. First-line use of the most effective drug would reduce medical and social costs. Societal willingness to pay for the vision benefit would equal the medical costs. Treatment initiated with the most effective drug is a cost saving strategy.

Conclusions: Public health decisions in glaucoma treatment should take a broad economic view embracing the lifetime duration of the disease. There is still a place both within and outside the healthcare system for therapeutic innovations with important economic consequences that bring high added value to patients.     

A review of international pharmacoeconomic models assessing the use of aspirin in primary prevention

Abstract

Purpose:

The aim of this narrative review was to summarise the cost analyses and supporting trial data for aspirin prophylaxis in primary prevention.

Methods:

A PubMed search using the term ‘aspirin and cost-effective and primary prevention’ was performed. Professional meetings (2009) were also searched for any relevant abstracts contacting the terms ‘aspirin’ and ‘cost effectiveness’. Where possible, outcomes were discussed in terms of cost implications (expressed as quality-adjusted life-year [QALY], disability-adjusted life-year or incremental cost-effectiveness ratio) in relation to the annual risk of cardiovascular disease. Aspirin was included in cost-effectiveness models that determined direct cost savings.

Results:

A total of 67 papers were identified using PubMed, and 17 cost-effectiveness studies, which assessed aspirin in primary prevention (largely based on the key primary prevention studies), and two abstracts were included in the review. These analyses showed that low-dose aspirin was cost effective in a variety of scenarios. In the UK, Germany, Spain, Italy and Japan, the mean 10-year direct cost saving (including follow-up costs and aspirin costs) per patient was €201, €281, €797, €427 and €889 with aspirin use in patients with an annual coronary heart disease risk of 1.5%. Cost-effectiveness analyses were affected by age, risk level for stroke and myocardial infarction (MI), risk of bleeds and adherence to aspirin. Underutilisation is a major limiting factor, as the appropriate use of aspirin in an eligible population (n?=?301,658) based on the NHANES database would prevent 1273 MIs, 2184 angina episodes and 565 ischaemic strokes in patients without previous events; this would result in a direct cost saving of $79.6?million (€54.7?million; 2010 values), which includes aspirin costs.

Conclusions:

Most analyses in primary prevention have shown that low-dose aspirin is a cost-effective option, and is likely to meet the willingness of a healthcare system to pay for any additional QALY gained in the majority of healthcare systems.     

Cost of adverse events during treatment with everolimus plus exemestane or single-agent chemotherapy in patients with advanced breast cancer in Western Europe

Objective:

Treatment options for recurrent or progressive hormone receptor-positive (HR+) advanced breast cancer include chemotherapy and everolimus plus exemestane (EVE?+?EXE). This study estimates the costs of managing adverse events (AEs) during EVE?+?EXE therapy and single-agent chemotherapy in Western Europe.

Methods:

An economic model was developed to estimate the per patient cost of managing grade 3/4 AEs for patients who were treated with EVE?+?EXE or chemotherapies. AE rates for patients receiving EVE?+?EXE were collected from the phase III BOLERO-2 trial. AE rates for single-agent chemotherapy, capecitabine, docetaxel, or doxorubicin were collected from published clinical trial data. AEs with at least 2% prevalence for any of the treatments were included in the model. A literature search was conducted to obtain costs of managing each AE, which were then averaged across Western European countries (when available). Per patient costs for managing AEs among patients receiving different therapies were reported in 2012 euros (€).

Results:

The EVE?+?EXE combination had the lowest average per patient cost of managing AEs (€730) compared to all chemotherapies during the first year of treatment (doxorubicin: €1230; capecitabine: €1721; docetaxel: €2390). The most costly adverse event among all patients treated with EVE?+?EXE was anemia (on average €152 per patient). The most costly adverse event among all patients treated with capecitabine, docetaxel, or doxorubicin was lymphocytopenia (€861 per patient), neutropenia (€821 per patient), and leukopenia (€382 per patient), respectively.

Conclusions:

The current model estimates that AE management during the treatment of HR+ advanced breast cancer will cost one-half to one-third less for EVE?+?EXE patients than for chemotherapy patients. The consideration of AE costs could have important implications in the context of healthcare spending for advanced breast cancer treatment.     

Costs of managing severe hypoglycaemia in three European countries

Abstract

Objectives: To assess the costs of severe hypoglycaemic events (SHEs) in diabetes patients in Germany, Spain and the UK.

Methods: Healthcare resource use was measured by surveying 639 patients aged ≥16 years, receiving insulin for type 1 (n=319) or type 2 diabetes (n=320), who experienced ≥1 SHE in the preceding year. Patients were grouped by location of SHE treatment: group 1, community (family/domestic); group 2, community (healthcare professional); group 3, hospital. Costs were calculated from published unit costs applied to estimated resource use. Costs per SHE were derived from patient numbers per subgroup. Weighted average costs were derived using a prevalence database.

Results: Hospital treatment was a major cost in all countries. In Germany and Spain, costs per SHE for type 1 patients differed from those for type 2 patients in each group. Average SHE treatment costs were higher for patients with type 2 diabetes (Germany, €533; Spain, €691; UK, €537) than type 1 diabetes patients (€441, €577 and €236, respectively). Telephone calls, visits to doctors, blood glucose monitoring and patient education contributed substantially to costs for non-hospitalised patients.

Conclusions: Treatment of SHEs adds significantly to healthcare costs. Average costs were lower for type 1 than for insulin-treated type 2 diabetes, in all three countries.     

Clinical and economic burden of extra-articular manifestations in ankylosing spondylitis patients treated with anti-tumor necrosis factor agents

Abstract

Objective:

To assess concomitant extra-articular manifestation (EAM) rates in patients with ankylosing spondylitis (AS) treated with anti-tumor necrosis factor (anti-TNF) agents and examine the economic burden of uveitis and inflammatory bowel disease (IBD) in French and German AS patients.

Methods:

Previous analyses of uveitis and IBD in AS patients treated with infliximab, etanercept or adalimumab were identified in PubMed/Medline (January 2000 to August 2011). A supplemental analysis incorporated more recent adalimumab clinical trial data (ATLAS [NCT00085644] and RHAPSODY [NCT00478660]). For resource utilization/costs associated with EAMs, the search was expanded to general spondyloarthritis (SpA) conditions (i.e., AS, reactive or psoriatic arthritis, psoriatic spondylitis, IBD and undifferentiated SpA). Direct and indirect yearly costs associated with AS-associated uveitis and IBD were estimated based on interviews with French and German clinicians and literature review.

Results:

The pooled average rate of anterior uveitis (AU) flares for patients treated with anti-TNF therapy in two meta-analyses and supplemental adalimumab clinical trials was 4.9/100-patient-years (PYs). AU rates (per 100-PYs) were 3.4, 3.7 and 5.7 for infliximab (p?=?0.26 vs etanercept; p?=?0.86 vs adalimumab), adalimumab (p?=?0.033 vs etanercept) and etanercept, respectively. IBD flares (per 100-PYs) were 0.2 for infliximab (p?<?0.001 vs etanercept; p?=?0.18 vs adalimumab), 0.63 for adalimumab (p?=?0.009 vs etanercept) and 2.2 for etanercept. No studies assessing EAM-associated resource utilization or costs in AS patients were found. Direct medical costs associated with IBD treatment ranged from €483 (Germany) to €6443 (France). Clinician-estimated AS-related uveitis direct medical costs were €1410 (Germany) and €1812 (France).

Conclusions:

Clinical data synthesis demonstrated significantly lower AU flare rates with adalimumab vs etanercept and significantly lower IBD rates with both adalimumab and infliximab vs etanercept. Economic analysis indicated substantial costs associated with AU and IBD flares secondary to AS in France and Germany. Future economic evaluations of anti-TNF agents should incorporate EAMs and subsequent treatment costs. Limitations include restricted availability of randomized, placebo-controlled clinical trial data, inclusion of data from open-label studies, lack of real-world (i.e., non-trial-based) EAM rates and a lack of EAM-specific direct and indirect costs with which to compare the results presented herein.     

Evaluation of cost savings with ferric carboxymaltose in anemia treatment through its impact on erythropoiesis-stimulating agents and blood transfusion: French healthcare payer perspective

Abstract

Objective:

To evaluate the economic impact of intravenous iron (in the form of intravenous iron preparation of ferric carboxymaltose) in three different clinical settings of iron deficiency anemia: chemotherapy-induced anemia in breast cancer, chemotherapy-induced anemia in digestive cancer, and perioperative anemia in knee and hip surgery.

Methods:

The economic model compared the usual therapeutic strategies of anemia without intravenous iron and strategies including intravenous iron, in each of the three clinical settings selected. Costs related to anemia treatment by erythropoiesis-stimulating agents (ESA), blood transfusion, and intravenous iron were estimated and compared inside each setting. Cost savings were calculated from the French healthcare payer perspective. Data included in the economic model were obtained from scientific literature, public health agencies, and medical experts.

Results:

The most prominent annual cost savings were observed in chemotherapy-induced anemia in breast cancer (€997 and €360 per patient for metastatic and non-metastatic breast cancers, respectively; global cost saving, €33.6 million). This large impact of intravenous iron on costs was mainly explained by both a lower number of women treated and lower ESA dosing. Mean annual cost saving in digestive cancers and knee and hip surgery were estimated to €168 and €216 per patient and global cost savings of €7.5 and €12.1 million, respectively. Overall, annual cost savings in these three settings were estimated to €53 million including €39 million for ESA cost savings. Sensitivity analysis showed that strategies including intravenous iron remained cost-effective even with wide variations in the assumptions, particularly for cost savings on ESA.

Limitations:

Economic model based on literature data and expert opinions.

Conclusions:

The present economic model suggests that use of intravenous iron, according to recommendations of international guidelines, is cost saving, particularly in chemotherapy-induced anemia in breast cancers.     

Evaluating drug cost per responder and number needed to treat associated with lixisenatide on top of glargine when compared to rapid-acting insulin intensification regimens on top of glargine,in patients with type 2 diabetes in the UK,Italy, and Spain

Objectives: This study investigated the cost per responder and number needed to treat (NNT) in type 2 diabetes mellitus (T2DM) patients for lixisenatide compared to insulin intensification regimens using composite endpoints in the UK, Italy, and Spain.

Methods: Efficacy and safety outcomes were obtained from GetGoal Duo-2, a 26-week phase 3 trial comparing lixisenatide vs insulin glulisine (IG) once daily (QD) and three times daily (TID). Response at week 26 was extrapolated to 52 weeks, assuming a maintained treatment effect, based on long-term evidence in other T2DM populations. Responders were defined using composite end-points, based on an HbA1c threshold and/or no weight gain and/or no hypoglycemia. The HbA1c threshold was varied in sensitivity analyses. Annual treatment costs were estimated in euros (1 GBP?=?1.26 EUR), including drug acquisition and resource use costs. Cost per responder was computed by dividing annual treatment costs per patient by the proportion of responders.

Results: Lixisenatide was associated with the lowest cost per responder for all composite end-points that included a weight-related component. For the main composite end-point of HbA1c ≤7.5% AND no weight gain AND no symptomatic hypoglycemia, cost per responder results were: UK: 6,867€, 8,746€, and 12,410€; Italy: 7,057€, 9,160€, and 12,844€; Spain: 8,370€, 11,365€, and 17,038€, for lixisenatide, IG QD, and TID, respectively. The NNT analysis showed that, for every 6.85 and 5.86 patients treated with lixisenatide, there was approximately one additional responder compared to IG QD and TID, respectively.

Limitations: A limitation of the clinical inputs is the lack of 52-week trial data from GetGoal Duo-2, which led to the assumption of a maintained treatment effect from week 26 to 52.

Conclusions: This analysis suggests lixisenatide is an efficient economic resource allocation in the UK, Italy, and Spain.     

Health economic evaluation of a vaccine for the prevention of herpes zoster (shingles) and post-herpetic neuralgia in adults in Belgium

Abstract

Objective:

To determine the cost-effectiveness of vaccination against herpes zoster (HZ) and post-herpetic neuralgia (PHN) in individuals aged 60 years and older in Belgium.

Methods:

A Markov model was developed to compare the cost-effectiveness of vaccination with that of a policy of no vaccination. The model estimated the lifetime incidence and consequences of HZ and PHN using inputs derived from Belgian data, literature sources, and expert opinion. Cost-effectiveness was measured by the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life-year (QALY) gained.

Results:

Vaccination in individuals aged 60 years and older resulted in ICERs of €6,799 (third party payer perspective), €7,168 (healthcare perspective), and €7,137 (societal perspective). The number needed to vaccinate to prevent one case was 12 for HZ, and 35 or 36 for PHN depending on the definition used. Univariate sensitivity analyses produced ICERs of €4,959–19,052/QALY; duration of vaccine efficacy had the greatest impact on cost-effectiveness. Probabilistic sensitivity analysis showed at least a 94% probability of ICERs remaining below the unofficial €30,000 threshold.

Discussion:

Key strengths of the model are the combination of efficacy data from a pivotal clinical trial with country-specific epidemiological data and complete sensitivity analysis performed. Main limitations are the use of non country-specific PHN proportion and non Belgian disease-specific utilities. Results are comparable with those recently published.

Conclusions:

HZ vaccination in individuals aged 60 years and older would represent a cost-effective strategy in Belgium.     

Cost-effectiveness of omalizumab for uncontrolled allergic asthma in the Netherlands

Abstract

Background:

Omalizumab, licensed for patients with uncontrolled persistent allergic (IgE mediated) asthma, was found to be cost-effective based upon its clinical trial data. Observational studies have been undertaken to determine the real life outcomes of using omalizumab in the community.

Objective:

To determine the cost-effectiveness of omalizumab based upon observational data from the Netherlands and compare to its cost-effectiveness using clinical trial data.

Methods:

An observational study (eXpeRience) recruited allergic asthma patients eligible for Omalizumab therapy and followed them while on treatment. At 1 year, data from the Dutch patients enrolled in eXpeRience were examined to estimate the number of exacerbations and resource use while on omalizumab therapy compared to the year prior to omalizumab use. Observational data were used in a Markov model to calculate the lifetime cost-effectiveness ratios.

Results:

In the 1 year prior to omalizumab therapy the per-person rate of exacerbations was 3.39 compared to 1.07 in the year taking omalizumab. The discounted incremental lifetime additional costs for omalizumab were €55,865 for 1.46 additional quality-adjusted life years (QALY), resulting in €38,371/QALY. Using the INNOVATE clinical trial outcomes and current resource use, the prior ratio was €34,911/QALY, similar to the observational ratio. As in all observational studies, the main limitation is obtaining complete and accurate data. Patients with missing exacerbation or response data were excluded from this analysis.

Conclusion:

Non-clinical trial experience with omalizumab supported the finding of fewer exacerbations in the allergic asthma population while treated with omalizumab, and therapy was found to continue to have an attractive cost-effectiveness ratio.     

Economic burden associated with the management of cervical cancer,cervical dysplasia and genital warts in Belgium

Abstract

Objective: Human papillomavirus (HPV) infections can lead to cervical intraepithelial neoplasia (CIN) lesions, cervical cancer (CC) and genital warts (GWs). This study intended to assess the annual cost of CC, CIN and GW management in Belgium.

Method: A retrospective study using a Belgian Hospital Disease Database (for yearly hospital cost of CC and GW patients) and a clinical expert survey were performed to assess the medical management of CC, CIN and GW patients. Belgian official sources were used to estimate the annual costs of management of CC, CIN and GW patients both from a healthcare payer perspectives (HCPP) and a societal perspective.

Results: Based on the 667 patients diagnosed annually in Belgium with CC and an annual cost per patient of €9,716, the total annual cost of CC is €6.5 million (HCPP). The 10,495 estimated CIN 1, 2 and 3 patients led to an annual cost of €1.97 million (HCPP). The 7,989 estimated annual number of diagnosed GW patients led to an estimated annual cost of €2.53 million (HCPP).

Conclusion: HPV-related diseases represent an important burden on Belgian society, especially when considering that the estimates in this study are probably underestimations, as the management costs of other HPV-related diseases (vulvar, vaginal, penile, oropharyngeal (pre-) cancers, recurrent respiratory papillomatosis etc.) are not included in this analysis.