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.     

Bambuterol is a more cost-effective treatment strategy than salmeterol in asthmatic patients with nocturnal symptoms

Summary

We aimed to compare the cost-effectiveness of oral bambuterol (Bambec®) 20?mg once daily with that of salmeterol (Serevent®) via pressurised metered dose inhaler (pMDI) 50?µg twice daily for treatment of asthma patients with nocturnal symptoms. One hundred and twenty six patients aged 18-70 years and using inhaled corticosteroids at a constant daily dose and with forced expiratory volume in one second (FEV1) 40-85% of predicted normal value, were included in this double-blind, randomised, parallel-group study (two weeks' run-in, six weeks' treatment) in the United Kingdom, Italy and Norway. During run-in, they had to have a nocturnal awakening or early awakening due to asthma symptoms that required rescue medication at least once during a two-week run-in period, and a > 15% fall in overnight peak expiratory flow (PEF) on at least three out of the last seven days. Morning and evening PEF were measured and tremor was scored. The effectiveness variables in the cost-minimisation analysis were symptom-free days and number of nights with no awakenings. Costs for both study and rescue medication were calculated.

There were no statistically significant differences between bambuterol and salmeterol regarding morning and evening PEF (change from baseline), tremor, and the effectiveness variables. Mean number of symptom-free days was 25% vs. 20% and mean number of nights with no awakenings was 69% vs. 77% in the bambuterol and salmeterol groups, respectively. However treatment costs (study plus rescue medication) were lower during bambuterol treatment in all three countries. The per patient cost savings would be 47% in the UK, 27% in Italy and 40% in Norway if a patient changes from salmeterol to bambuterol. The conclusion is that the once-daily treatment with bambuterol is more cost-effective than the twice-daily treatment with salmeterol in asthma patients with nocturnal symptoms.     

A PCT algorithm for discontinuation of antibiotic therapy is a cost-effective way to reduce antibiotic exposure in adult intensive care patients with sepsis

Abstract

Objective:

Procalcitonin (PCT) is a specific marker for differentiating bacterial from non-infective causes of inflammation. It can be used to guide initiation and duration of antibiotic therapy in intensive care unit (ICU) patients with suspected sepsis, and might reduce the duration of hospital stay. Limiting antibiotic treatment duration is highly important because antibiotic over-use may cause patient harm, prolonged hospital stay, and resistance development. Several systematic reviews show that a PCT algorithm for antibiotic discontinuation is safe, but upfront investment required for PCT remains an important barrier against implementation. The current study investigates to what extent this PCT algorithm is a cost-effective use of scarce healthcare resources in ICU patients with sepsis compared to current practice.     

Use of insertable cardiac monitors for the detection of atrial fibrillation in patients with cryptogenic stroke in the United States is cost-effective

Abstract

Objectives: Atrial fibrillation (AF) is the most common arrhythmia and a major marker of ischemic stroke risk. Early detection is crucial and, once diagnosed, anticoagulation therapy can be initiated to reduce stroke risk. The aim of this study was to assess the cost-effectiveness of employing an insertable cardiac monitor (ICM), BIOMONITOR, for the detection of AF compared to standard of care (SoC) ECG and Holter monitoring in patients with cryptogenic stroke, that is, stroke of unknown origin and where paroxysmal, silent AF is suspected.

Materials and methods: A Markov model was developed which consisted of five main health states reflecting the potential lifetime evolution of the AF disease: post cryptogenic stroke (index event), subsequent mild, moderate and severe stroke, and death. Sub-states were included to track a patient’s AF diagnostic status and the use of antiplatelet or anticoagulant therapy. AF detection was assumed to result in a treatment switch from aspirin to anticoagulants, except among those with a history of major bleeding. Detection yield and accuracy, clinical actions and treatment effects were derived from the literature and validated by an expert clinician. All relevant costs from a US Medicare perspective were included.

Results and conclusions: An ICM-based strategy was associated with a reduction of 37 secondary ischemic strokes per 1000 patients monitored compared with SoC. Total per-patient costs with an ICM were higher (US$90,052 vs. US$85,157) although stroke-related costs were reduced. The use of an ICM was associated with a base-case incremental cost-effectiveness ratio of US$18,487 per life year gained compared with SoC and US$25,098 per quality-adjusted life year gained, below established willingness-to-pay thresholds. The conclusions were found to be robust over a range of input values. From a US Medicare perspective the use of a BIOMONITOR ICM represents a cost-effective diagnostic strategy for patients with cryptogenic stroke and suspected AF.     

Ultrafiltration versus diuretics for the treatment of fluid overload in patients with heart failure: a hospital cost analysis

Abstract

Background: Heart failure (HF) is a common, serious disease in the US and Europe. Patients with HF often require treatment for fluid overload, resulting in costly inpatient visits; however, limited evidence exists on the costs of alternative treatments. This study performed a cost-analysis of ultrafiltration (UF) vs diuretic therapy (DIUR-T) for patients with HF from the hospital perspective.

Methods: The model used clinical data from the literature and hospital data from the Healthcare Cost and Utilization Project to follow a decision-analytic framework reflecting treatment decisions, probabilistic outcomes, and associated costs for treating patients with HF and hypervolemia with veno-venous UF or intravenous DIUR-T. A 90-day timeframe was considered to account for hospital readmissions beyond 30?days. Sensitivity and scenario analyses were performed to gauge the robustness of the results.

Results: Although initial hospitalization costs were higher, fluid removal by UF reduced hospital readmission days, leading to cost savings of $3,975 (14.4%) at the 90-day follow-up (UF costs, $23,633; DIUR-T costs, $27,608).

Conclusions: UF is a viable alternative to DIUR-T when treating fluid overload in HF patients because it reduces hospital readmission rates and durations, which substantially lowers costs over a 90-day period compared to DIUR-T.     

A cost-effectiveness analysis of MMX mesalazine compared with mesalazine in the treatment of mild-to-moderate ulcerative colitis from a UK perspective

Abstract

Objectives: To perform a cost-utility analysis of a new formulation of mesalazine (Mezavant XL, MMX mesalazine) versus an existing oral mesalazine (Asacol; mesalazine) from the UK National Health Service perspective.

Methods: A 5-year Markov cohort model was developed. Costs were obtained from the literature and utilities from an independent study. Uncertainty was evaluated using one-way and probabilistic sensitivity analyses (PSA). The potential effect of dosing frequency on adherence and possible long-term effects of remission maintenance on colorectal cancer (CRC) rates were also investigated.

Results: The model suggested that 5-year therapy with MMX mesalazine was likely to generate gains when compared with mesalazine, including a gain of 0.011 QALYs per patient, 19 more remission days, and 12% fewer hospitalizations and surgical episodes. These gains came at an increase in total NHS direct cost of £8, resulting in an incremental cost-effectiveness ratio (ICER) of £749. The PSA suggested that MMX mesalazine had a 62% chance of resulting in cost savings, and a 74% chance of being cost effective (£20,000 threshold). Extended analysis including adherence and CRC effects suggested further incremental benefit of MMX mesalazine over mesalazine could be expected. Limitations include uncertainty in extrapolation to a 5-year time horizon and impact of adherence and drug acquisition costs on outcomes.

Conclusion: The pharmacoeconomic analysis suggested that MMX mesalazine is likely to produce small, but worthwhile, increases in total NHS direct cost while increasing time in remission and associated quality of life, when compared with mesalazine. Advantages in adherence to treatment with MMX mesalazine relative to mesalazine suggested that further health gains and cost savings can be obtained. Overall, these results suggest that MMX mesalazine is a cost-effective treatment for UC.     

Costs of haematological adverse events in chronic myeloid leukaemia patients: a retrospective cost analysis of the treatment of anaemia,neutropenia and thrombocytopenia in patients with chronic myeloid leukaemia

Abstract

Objective: The study aim was to assess costs of haematological adverse events (AE) related to pharmacologic treatment of chronic myeloid leukaemia (CML) patients.

Methods: This was a retrospective cohort study using patient records of adults (n=91) with chronic-phase CML treated at a single university medical centre in the Netherlands. Occurrence of grade III/IV haematological AEs, defined according to CTC-NCI guidelines criteria, was derived from the laboratory registration. Mean age at time of diagnosis was 48 years; 56% male. A healthcare perspective was adopted. Cost estimates are presented in 2006 euros.

Results: Average cost of an episode of anaemia was €1,572, of thrombocytopenia €2,955, and of neutropenia €1,152. The mean cost of febrile neutropenia amounted to €2,462.

Conclusions: Treatment costs of AEs varied considerably. However, apart from the cost of anaemia, the results presented seem to be in line with information from the international literature. The key limitations of the study concern the relatively small cohort of patients at a single centre, the retrospective design and the various treatment regimens of CML during the follow-up.     

Irbesartan and amlodipine in the treatment of patients with microalbuminuria,hypertension and type 2 diabetes in Taiwan: a modelling projection over 25 years

Summary

This modelling study aimed to evaluate the long-term cost effectiveness of four treatment strategies: early irbesartan; late irbesartan; amlodipine; and standard hypertensive treatment in patients with diabetes, hypertension and microalbuminuria in Taiwan. A Markov model was used to project costs and clinical outcomes over lifetimes.

Early irbesartan (initiated in microalbuminuric patients) yielded the largest improvements in life expectancy (0.78 years) compared with standard treatment. Late irbesartan and amlodipine (started in patients with overt nephropathy) also resulted in slight improvements in life expectancy (0.109 and 0.001 years, respectively). Both early and late irbesartan reduced lifetime costs compared with control (US$7,603 and US$3,233, respectively), whereas amlodipine increased lifetime costs by US$300. Improvements were attributed to reductions in the cumulative incidence of end-stage renal disease with early use of irbesartan.

Treating hypertensive diabetic patients with early irbesartan was projected to be life extending and cost saving, and to reduce the incidence of ESRD in Taiwan.     

A cost comparison of long-acting insulin analogs vs NPH insulin-based treatment in patients with type 2 diabetes using routinely collected primary care data from the UK

Abstract

Aim:

The aim of this analysis was to investigate total healthcare costs, HbA1c, and weight changes over a 36-month period in patients with type 2 diabetes initiated on NPH or long-acting insulin analogs.

Methods:

Electronic patient data from 479 general practices in the UK (THIN database) were examined for new users of glargine (n?=?794), detemir (n?=?252), or NPH insulin (n?=?430). Annualized healthcare costs and clinical outcomes in years 1, 2, and 3 following insulin initiation were quantified and compared with baseline, using ANOVA and linear regression models.

Results:

A significant difference (p?<?0.05) in total healthcare costs increases at year 1 vs baseline was observed between glargine and detemir, detemir and NPH, but not between glargine and NPH (increase: +£486, +£635, and +£420 for glargine, detemir, and NPH users, respectively). However, increases by year 3 were not significantly different between the insulins. A propensity score analysis comparing analog and NPH insulin showed that, following insulin initiation, increases in costs were higher with insulin analogs at year one (+£220), but this difference decreased over time in each year following insulin initiation (+£168 and +£146, respectively, for years 2 and 3). HbA1c reductions were not significantly different between the groups at all time points. Differences in weight gain between glargine and NPH were statistically significant at year 1 (0.87?kg vs 1.11?kg) and year 3 (1.15?kg vs 1.57?kg), but other estimates of between-group differences in weight gain were non-significant.

Conclusions:

Following insulin initiation, the difference in healthcare costs of long-acting analogs compared to NPH insulin was transient. By year 3, the cost differences were not significantly different between the two cohorts, driven by an observed reduction in the cost of self-monitoring of blood glucose (SMBG) in the analog group and an increase in the cost of bolus insulin in the NPH group.     

Development of a health economic model to evaluate the potential benefits of optimal serum potassium management in patients with heart failure

Abstract

Aims: Patients with heart failure are at increased risk of hyperkalemia, particularly when treated with renin-angiotensin-aldosterone system inhibitor (RAASi) agents. This study developed a model to quantify the potential health and economic value associated with sustained potassium management and optimal RAASi therapy in heart failure patients.

Materials and methods: A patient-level, fixed-time increment stochastic simulation model was designed to characterize the progression of heart failure through New York Heart Association functional classes, and predict associations between serum potassium levels, RAASi use, and consequent long-term outcomes. Following internal and external validation exercises, model analyses sought to quantify the health and economic benefits of optimizing both serum potassium levels and RAASi therapy in heart failure patients. Analyses were conducted using a UK payer perspective, independent of costs and utilities related to pharmacological potassium management.

Results: Validation against multiple datasets demonstrated the predictive capability of the model. Compared to those who discontinued RAASi to manage serum potassium, patients with normokalemia and ongoing RAASi therapy benefited from longer life expectancy (+1.38 years), per-patient quality-adjusted life year gains (+0.53 QALYs), cost savings (£110), and associated net monetary benefit (£10,679 at £20,000 per QALY gained) over a lifetime horizon. The predicted value of sustained potassium management and ongoing RAASi treatment was largely driven by reduced mortality and hospitalization risks associated with optimal RAASi therapy.

Limitations: Several modeling assumptions were made to account for a current paucity of published literature; however, ongoing refinement and validation of the model will ensure its continued accuracy as the clinical landscape of hyperkalemia evolves.

Conclusions: Predictions generated by this novel modeling approach highlight the value of sustained potassium management to avoid hyperkalemia, enable RAASi therapy, and improve long-term health economic outcomes in patients with heart failure.     

Cost-effectiveness of obinutuzumab plus bendamustine followed by obinutuzumab monotherapy for the treatment of follicular lymphoma patients who relapse after or are refractory to a rituximab-containing regimen in the US

Aims: Obinutuzumab (GA101, G) was approved in February 2016 by the US Food and Drug Administration to treat follicular lymphoma (FL) patients who relapsed after, or are refractory to (R/R), a rituximab-containing regimen (R/R-rituximab). In the GADOLIN trial, R/R-rituximab patients who received G plus bendamustine (B) followed by G-monotherapy (G?+?B) for up to 2 years had significantly improved progression-free survival and overall survival compared to patients receiving B-monotherapy. This study estimated the cost-effectiveness of G?+?B vs B-monotherapy for R/R-rituximab FL patients from a US payer perspective.

Materials and methods: Patient outcomes were simulated using a 3-state area under the curve model including progression-free survival, progressive disease, and death. This study used R/R-rituximab data from the National LymphoCare Study to extrapolate the GADOLIN trial’s refractory FL progression-free and overall survival data to a R/R-rituximab FL population. Drug utilization and adverse events were based on trial data, and costs were based on Medicare reimbursements and drug wholesale acquisition costs in 2016. Utility estimates were derived from published literature. Post-progression treatment costs were based on observed post-progression therapies in GADOLIN. Sensitivity analyses were conducted to assess model uncertainty.

Results: G?+?B resulted in an increase in quality-adjusted life years relative to B-monotherapy of 1.24 (95% CR?=?0.61–1.87); the incremental total cost was $58,100 (95% CR?=?$54,500–$61,500). The incremental cost-effectiveness ratio was $47,000 per QALY gained, and, based on probabilistic simulations, there was a 98% probability that G?+?B was cost-effective at the $100,000 per QALY threshold.

Limitations and conclusions: This US-based analysis suggests that treatment with G?+?B compared to B-monotherapy is likely cost-effective in R/R-rituximab FL patients. Modeling a R/R-rituximab population based on a synthesis of GADOLIN and the National LymphoCare Study data introduces uncertainty in the analysis. However, the findings were robust to sensitivity analyses.     

Modelling the economic impact of recombinant activated Factor VII compared to activated prothrombin-complex concentrate in the home treatment of a mild to moderate bleed in adults with inhibitors to clotting Factors VIII and IX in the UK

Summary

This study estimated the costs and consequences of using recombinant activated Factor VII (rFVIIa; NovoSeven®) at home, compared to activated prothrombin-complex concentrate (aPCC; FEIBA®*) at home, to manage a minor (i.e. mild to moderate) bleeding episode in adults with high titre, high responding inhibitors (>10 BU). The analysis was performed from the perspective of the UK's National Health Service (NHS).

NovoSeven and FEIBA are registered trademarks of Novo Nordisk and Baxter Healthcare, respectively.

Clinical outcomes and resource utilisation attributable to managing a minor bleed were obtained from published literature, supplemented with information about treatment patterns and associated resource utilisation derived from interviews with a panel of 22 consultant haematologists experienced in managing inhibitor patients. Using these data sources a decision tree modelling the management of a minor bleed, initially at home, was constructed. Unit resource costs at 1999/2000 prices were applied to the resource utilisation estimates in the model to estimate the expected NHS cost of managing a minor bleeding episode. Consensus on the probabilities and resource utilisation estimates in the model were reached at a meeting comprising seven panel members.

The expected NHS cost of managing a minor bleeding episode initially treated with rFVIIa or aPCC at home was estimated to be £12,944 and £14,645, respectively. Additionally, the expected time to resolving a minor bleeding episode when initially treated with rFVIIa or aPCC at home was estimated to be 32 hours and 60 hours, respectively. Hence, rFVIIa improves clinical outcome compared to aPCC, but at no additional cost to the NHS, resulting in rFVIIa being the cost-effective treatment. This finding warrants further investigation in a prospective, comparative, randomised, controlled study.     

Indirect comparison of the effects of anti-TNF biological agents in patients with Ankylosing Spondylitis by means of a Mixed Treatment Comparison performed on efficacy data from published randomised,controlled trials

Abstract

Objectives:

To compare ASAS (Assessment in Ankylosing Spondylitis Response Criteria), 20 response patterns between anti-TNF biological agents in patients with ankylosing spondylitis by means of a mixed treatment comparison of different randomized, controlled trials (RCTs) on the efficacy of biological therapies.

Methods:

A systematic review of literature was performed to identify a number of similarly designed double-blind, randomized, placebo-controlled trials investigating the efficacy of the TNF-α inhibitors etanercept, infliximab, and adalimumab in the treatment of ankylosing spondylitis patients, conducted over an 18-year period. The end-point of interest was ASAS20 response criteria at 24 weeks. Results were analyzed simultaneously using Bayesian mixed treatment comparison techniques. Results were expressed as odds ratio (OR) of ASAS20 response and associated 95% credible intervals (CrIs). The probability of being the best treatment was also reported.

Results:

Three RCTs were selected for data extraction and further analysis. By mean of MTC, all anti-TNF agents demonstrated to be more efficacious in inducing an ASAS20 response than placebo. Infliximab shows a 72% probability of being the best treatment of all. Adalimumab and etanercept show probabilities of 13% and 15%, respectively. No differences were observed when comparing directly an anti-TNF-α agent against another. When compared with placebo, Infliximab increases the probability of response by ～7-times (OR?=?6.8), Adalimumab by ～4-times (OR?=?4.4), and Etanercept by 5-times (OR?=?4.9). Differences in trials procedures, the use of a fixed-effect model, and the small number of trials included represent limitations of this study

Conclusions:

Even if the mixed treatment comparisons between infliximab, adalimumab, and etanercept did not show a statistically signi?cant difference, this analysis suggests that infliximab, compared to placebo, is expected to provide the highest rate of ASAS20 response in SA patients naive to biologic treatments.