UK cost-utility analysis of rituximab in patients with rheumatoid arthritis that failed to respond adequately to a biologic disease-modifying antirheumatic drug

ABSTRACT

Objective: To evaluate the incremental cost effectiveness of rituximab in patients with rheumatoid arthritis that failed to respond adequately to tumour necrosis factor-α inhibitors (biologic disease-modifying antirheumatic drugs; bDMARDs). A cost-utility model has been developed to simulate the long-term incremental cost and benefits of rituximab using data from clinical trials and registries.

Methods: The model estimates the lifetime disease progression of up to 10 000 hypothetical rheumatoid arthritis (RA) patients that failed one bDMARD. It compares cost and outcomes of two treatment sequences, representing the current UK standard both with and without rituximab. The population characteristics match those of the Randomised Evaluation of Long-term Efficacy of rituximab in RA (REFLEX) phase III randomised control trial. Clinical outcomes were based on an indirect comparison of published American College of Rheumatology response rates, adjusted for differences in placebo. To estimate medical resource use, health assessment questionnaire (HAQ) scores were grouped into five categories with UK registry data informing the average cost for each category. Quality-adjusted life years (QALYs) gained were mapped from disease severity (HAQ scores).

Results: Compared to a standard UK treatment sequence (assuming the sequential use of bDMARDs) the introduction of rituximab led to a QALY gain of 0.526 years. The incremental cost-effectiveness ratios (ICERs) based on total direct medical cost were £11 601. Adding rituximab to a treatment sequence with no sequential use of biologic generates an ICER of £14 690.

Conclusion: Rituximab has lower average annual treatment costs compared to other bDMARDs and is a highly cost-effective treatment option for patients who have failed to respond adequately to one bDMARD. The cost per QALY gained of rituximab falls well below commonly accepted thresholds within the UK. Potential weaknesses of the model include the paucity of data on the efficacy of bDMARDs or non-biologic DMARDs when used as second-line options; the lack of consensus about the most appropriate therapy in patients who fail all available bDMARDs; probable underestimation of the non-drug related medical costs; indirect measurement of QALY gains with rituximab therapy; and the necessity of synthesising data from a number of clinical trials with different populations and study drugs.     

托法替布治疗类风湿关节炎的快速卫生技术评估

目的:利用快速卫生技术评估(health technology assessment,HTA)的方法,定量地评价托法替布用于类风湿关节炎(RA)患者的有效性、安全性、经济性,针对托法替布在临床应用的实际情况,为临床实践、药物遴选和准入决策提供循证证据.方法:系统检索2019年5月31日前发表的HTA报告、系统评价/Me...     

Estimating the potential savings with vagus nerve stimulation for treatment-resistant depression: a payer perspective*

ABSTRACT

Objective: To provide a formula estimating potential reductions in healthcare utilization costs with adjunctive vagus nerve stimulation (VNS Therapy^?) in treatment-resistant depression (TRD).

Methods: This payer-perspective formula incorporates costs of treatment as usual for TRD patients from a published analysis of the MarketScan private payer claims database and the 2004 Medicare 5% standard analytic file. Estimated remission and response rates are from the published VNS pilot and pivotal studies. Costs were converted to 2008 US dollars per the US Bureau of Labor Statistics medical care costs, consumer price index. Device and implantation costs were calculated at $28?336.

Results: From the MarketScan and pooled outcomes data (VNS pilot and pivotal studies), potential per patient savings (hospitalization directly and indirectly related to depression) was $2974 at 5 years of device life, $23?539 at 8 years (moderate cost reduction scenario); $12?914 at 5 years, $40?935 at 8 years (optimistic scenario). Corresponding break-even device life was 4.57 and 3.62 years, respectively. From the Medicare file and pooled outcomes, potential per patient savings (inpatient and outpatient directly and indirectly related to depression) was $8358 at 5 years of device life, $32?385 at 8 years (moderate scenario); $19?837 at 5 years, $52?473 at 8 years (optimistic scenario). Corresponding break-even device life was 3.96 and 3.18 years, respectively.

Conclusions: The formula allows an evaluation of expected reductions in healthcare costs as a function of input cost variables, efficacy rates, and benefit scenarios. Cited costs differ relative to care settings, diagnostic principles, and procedural volume. This formula can help assess moderate-to-longer-term economic benefits of VNS for a particular institution. Results suggested that potential reductions in healthcare costs with VNS for TRD may be substantial. Break-even device life for the scenarios presented ranges between 2.3 and 5.7 years.

Trial registration: ClinicalTrials.gov identifier: NCT00533832.     

A review of tofacitinib efficacy in rheumatoid arthritis patients who have had an inadequate response or intolerance to methotrexate

Introduction: Tofacitinib is a pan JAK inhibitor with specificity for JAK3 over JAK1 over JAK2, which is approved in many countries for the treatment of rheumatoid arthritis (RA), including the United States and the European Union, either as monotherapy or in combination with conventional synthetic disease modifying anti-arthritis drugs (csDMARDs). Phase 2, 3 and 4 clinical trials have investigated the efficacy and safety of tofacitinib given either as monotherapy or in combination with csDMARDs.

Areas covered: This review reports the safety, clinical, functional, and radiographic efficacy, of tofacitinib used as monotherapy in the treatment of adult patients with RA reported in the prospective, double-blind, controlled randomized trials reported to date. One critical clinical question is whether tofacitinib monotherapy has similar efficacy as tofacitinib in combination with methotrexate (MTX); this question has recently been addressed. A literature search on tofacitinib monotherapy was carried out using the PubMed database up to July 2017.

Expert opinion: Although tofacitinib plus MTX is statistically more clinically effective, tofacitinib monotherapy is effective in many patients with RA.     

Cost–utility comparison of escitalopram and sertraline in the treatment of major depressive disorder

ABSTRACT

Objective: To construct a cost–utility model comparing escitalopram with sertraline in the treatment of major depressive disorders.

Methods: A decision analytic model was created to compare the cost–utility of these two antidepressants from the perspective of a managed-care organization. The model was designed to compare 10–20?mg/day of escitalopram to 50–200?mg/day of sertraline. Benefits (utility) scores were calculated based on clinical and utility data obtained from the literature. Direct medical costs included costs of the antidepressants, titration, treatment failures, and adverse events. Costs and benefits were modeled for a 6-month period and the model was subjected to thorough sensitivity analyses.

Results: The estimated 6-month total cost was $919 for escitalopram and $1351 for sertraline. The estimated QALYs were 0.40296 for escitalopram and 0.39268 for sertraline. These differences were mostly due to differences in drug acquisition costs and adverse events. The robustness of the cost–utility model results were tested in a Monte Carlo simulation of 10?000 patients and it indicated an 88.5% probability that escitalopram was the dominant therapy, suggesting both lower costs and greater QALYs.

Conclusion: This cost–utility model that incorporated the costs of titration and impact of side-effects comparing escitalopram 10–20?mg per day and sertraline 50–200?mg per day shows that escitalopram appeared to be less costly and produced efficacy (utility) at least as good as and maybe slightly better than that of sertraline.     

Estimating the economic impact of a half-day reduction in length of hospital stay among patients with community-acquired pneumonia in the US

ABSTRACT

Background: A recent study suggested that levofloxacin significantly reduces the hospital length of stay (LOS), by 0.5 days (p?=?0.02), relative to moxifloxacin in patients with community-acquired pneumonia (CAP). The current analysis evaluated the potential economic impact of this half-day reduction in LOS.

Methods: A cost model was developed to estimate the impact of a half-day reduction in LOS for CAP hospitalizations in the US. CAP incidence, hospitalization rate, and costs were obtained from published studies in PubMed and from publicly available government sources. The average daily cost of hospitalization was estimated for fixed costs, which comprise 59% of total inpatient costs. Costs from prior years were inflated to 2007 US dollars using the consumer price index. A range of cost savings, calculated using inpatient CAP costs from several studies, was extrapolated to the US CAP population.

Results: Using the Centers for Disease Control National Hospital Discharge estimate of 5.3 days LOS for CAP, and an average cost (2007 $US) of $13,009 per CAP hospitalization, a daily fixed cost of $1448 was estimated. The resultant half-day reduction in costs associated with LOS was $724/hospitalization (range $457 to $846/hospitalization). When fixed and variable costs were considered, the estimated savings were $1227.27/episode. The incidence of CAP was estimated to be 1.9% (5.7 million cases/year based on current population census), and the estimated rate of CAP hospitalization was 19.6% (1.1 million annual hospitalizations). At $13,009/CAP-related hospitalization, total fixed inpatient costs of $8.6 billion annually were projected. The half-day reduction in LOS would therefore generate potential annual savings of approximately $813 million (range $513 million to $950 million). When total costs (fixed plus variable) were estimated, the mean savings for a half-day reduction would be approximately $1227/episode (range of $775 to $1434) or $1.37 billion annually in the US CAP population (range of $871 million to $1.6 billion). Limitations include the use of a single study for the estimation of fixed costs but a diversity of sources used for estimates of other variables, and lack of data with respect to the effects on costs of diagnostic-related groups, discounted contracts, and capitated payments.

Conclusions: A relatively small decrease in LOS in CAP can have a substantial cost impact, with estimated savings of $457 to $846 per episode or $500-$900 million annually. Additional evaluation is warranted for interpreting these cost-savings in the context of current antibiotic prescribing patterns.     

Will insomnia treatments produce overall cost savings to commercial managed-care plans? A predictive analysis in the United States

ABSTRACT

Objective: Research indicates that insomnia may contribute significantly to healthcare costs; however, information on the effects of treatments on costs has not been thoroughly published. This study presents predictive models that forecast, from the perspective of commercial managed care, the effects of insomnia medications in reducing overall medical costs. The main objectives of this study were to predict the level of cost savings associated with insomnia treatments, illustrate the variation in outcomes given underlying model assumptions, and assist managed-care policy-makers with the evaluation of medications routinely administered for insomnia.

Methods: Data on four primary-efficacy measures: wake after sleep onset (WASO), sleep efficiency (SE), sleep onset latency (SOL) and total sleep time (TST) were abstracted from published clinical trial data for eszopiclone, indiplon, low-dose trazodone, ramelteon, zaleplon, zolpidem and zolpidem extended-release. Change in per-patient per-year (PPPY) healthcare costs in a single claims database was calculated for subjects taking zolpidem, zaleplon and low-dose trazodone using generalized linear model (GLM) techniques, controlling for baseline demographics and baseline costs. Change in costs for emerging insomnia medications was forecasted by imputing efficacy values for these drugs into the regressions.

Results: Using the accepted efficacy measure, WASO, zolpidem extended-release had the overall forecasted savings of –$1253 (CI: –$1404 to –$1404) PPPY compared to remaining treatments, whereas ramelteon cost an additional $348 (–$1280 to $584) PPPY. In three out of four cost-efficacy models, zolpidem extended-release had higher mean forecasted PPPY savings.

Conclusion: This study examined cost effects of existing and emerging insomnia medications using models integrating clinical literature and medical claims within a statistical framework. The use of a single database may limit generalizability and models only address a 1?year period. Results suggest treatments can offer health plans direct cost savings, with amounts sensitive to variable and efficacy measures, potentially limited by those variables available in the claims database. Compared to other evaluated treatments, zolpidem extended-release produced consistently higher predicted cost savings.     

Cost-effectiveness of the two-compound formulation calcipotriol and betamethasone dipropionate compared with commonly used topical treatments in the management of moderately severe plaque psoriasis in Scotland

ABSTRACT

Objectives: To determine the cost-effectiveness of calcipotriol/betamethasone dipropionate (Dovobet) in the initial treatment of moderate severity plaque psoriasis vulgaris in Scotland.

Research design and methods: An economic model was developed to simulate the costs and benefits of the most commonly used topicals in the management of plaque psoriasis. This was informed by an indirect unadjusted comparison of the effectiveness data to determine the relative efficacy of commonly used topicals. The model estimated their impact on costs and utility gain over a 1-year period. We accounted for direct medical costs from a health payer perspective. The cost–utility analysis included pharmacy costs and costs of failure of topicals in primary care in terms of secondary-care referrals for phototherapy. Extensive sensitivity analyses were undertaken to address areas of uncertainty in the parameters of the model.

Results: Patients treated with the two-compound formulation (TCF) of calcipotriol and betamethasone dipropionate (BDP) experienced better control of their psoriasis. In our model, this translated into reduced costs, as patients were less likely to be referred for phototherapy, and increased quality adjusted life years (QALYs) relative to other commonly used topicals. The TCF was estimated to generate annual savings ranging from £96 to £276 per patient per year compared to the other commonly used alternative topicals. With reduced costs and superior outcomes, the TCF ‘dominated’ these other treatments since the latter were associated with higher cost and lower utility or QALY gain. The model findings were not influenced by changes to a range of model input parameters within plausible limits.

Conclusions: Use of the TCF in patients with plaque psoriasis represents excellent value for money by delivering savings to the National Health Service (NHS) in Scotland. Similar findings are predicted for the management of psoriasis patients elsewhere in the UK.     

Evaluation of the cost-effectiveness of rifaximin-α for the management of patients with hepatic encephalopathy in the United Kingdom

Objective: Rifaximin-α 550?mg twice daily plus lactulose has demonstrated efficacy in reducing recurrence of episodes of overt hepatic encephalopathy (OHE) and the risk of hepatic encephalopathy (HE)-related hospitalizations compared with lactulose alone. This analysis estimated the cost effectiveness of rifaximin-α 550?mg twice daily plus lactulose versus lactulose alone in United Kingdom (UK) cirrhotic patients with OHE.

Method: A Markov model was built to estimate the incremental cost-effectiveness ratio (ICER). The perspective was that of the UK National Health Service (NHS). Clinical data was sourced from a randomized controlled trial (RCT) and an open-label maintenance study in cirrhotic patients in remission from recurrent episodes of OHE. Health-related utility was estimated indirectly from disease-specific quality of life RCT data. Resource use data describing the impact of rifaximin-α on hospital admissions and length of stay for cirrhotic patients with OHE was from four single-center UK audits. Costs (2012) were derived from published sources; costs and benefits were discounted at 3.5%. The base-case time horizon was 5 years.

Results: The average cost per patient was £22,971 in the rifaximin-α plus lactulose arm and £23,545 in the lactulose arm, a saving of £573. The corresponding values for benefit were 2.35 quality adjusted life years (QALYs) and 1.83 QALYs per person, a difference of 0.52 QALYs. This translated into a dominant base-case ICER. Key parameters that impacted the ICER included number of hospital admissions and length of stay.

Conclusion: Rifaximin-α 550?mg twice daily in patients with recurrent episodes of OHE was estimated to generate cost savings and improved clinical outcomes compared to standard care over 5 years.     

A cost-effectiveness analysis of pioglitazone plus metformin compared with rosiglitazone plus metformin from a third-party payer perspective in the US*

ABSTRACT

Objective: The long-term cost-effectiveness of using pioglitazone plus metformin (Actoplusmet^?) compared with rosiglitazone plus metformin (Avandamet^?) in treating type 2 diabetes (T2DM) was assessed from a US third-party payer perspective.

Research design and methods: Clinical efficacy (change in HbA_1c and lipids) and baseline cohort parameters were extracted from a 12-month, randomized clinical trial (Derosa et al., 2006) evaluating the efficacy and tolerability of pioglitazone versus rosiglitazone, both in addition to metformin, in adult T2DM patients with insufficient glucose control (n?=?96). A Markov-based model was used to project clinical and economic outcomes over 35 years, discounted at 3% per annum. Costs for complications were taken from published sources. Base-case assumptions were assessed through several sensitivity analyses.

Main outcome measures: Outcomes included incremental life-years, quality-adjusted life-years (QALYs), total direct medical costs, cumulative incidence of complications and associated costs, and incremental cost–effectiveness ratios (ICERs).

Results: Compared to rosiglitazone plus metformin, pioglitazone plus metformin was projected to result in a modest improvement in 0.187 quality-adjusted life-years. Over patients’ lifetimes, total direct medical costs were projected to be marginally lower with pioglitazone plus metformin (difference –$526.), largely due to reduced CVD complication costs. While costs were higher among renal, ulcer/amputation/neuropathy, and eye complications in the pioglitazone plus metformin group, the cost savings for CVD complications outweighed their economic impact. Pioglitazone plus metformin was found to be a dominant long-term treatment strategy in the US compared to rosiglitazone plus metformin. Sensitivity analyses showed findings to be robust under almost all scenarios, including short-term time horizons, 6% discounting, removal of individual lipid parameters, and modifications of patient cohort to more closely represent a US T2DM population. Pioglitazone plus metformin was no longer dominant with 0% discounting, with 25% reduction in its HbA_1c effects, or with a 15% increase in its acquisition price.

Conclusions: Under a range of assumptions and study limitations around cohorts, clinical effects, and treatment patterns, this long-term analysis showed that pioglitazone plus metformin, when compared to rosiglitazone plus metformin, was a dominant treatment strategy within the US payer setting. Results were driven by the combination of modest differences in QALYs and modest savings in total complication costs over 35 years.     

An economic evaluation of sevelamer in patients new to dialysis

ABSTRACT

Objective: The overall objective of this study was to estimate the costs and outcomes associated with treatment with sevelamer for hyperphosphataemia compared with calcium-based binders.

Methods: Using published data on mortality and hospitalisation rates, a Markov model was developed to predict health outcomes and associated costs for the treatment of hyperphosphataemia using either sevelamer or calcium binders in chronic kidney disease patients who had recently started haemodialysis. Patient outcomes were modelled for 5 years, and incremental cost-effective ratios (ICERs) were calculated for sevelamer relative to calcium carbonate and calcium acetate binders. The perspective adopted was that of the UK National Health Service.

Results: The total 5-year discounted treatment cost for patients treated with sevelamer is £24?216, while for the calcium carbonate group total cost was £17?695. This is an incremental cost of £6521 per sevelamer-treated patient over 5 years. Patients receiving sevelamer can be expected to experience 2.70 quality-adjusted life years (QALYs) compared to 2.46 for those treated with calcium carbonate (i.e. an incremental gain of 0.24 QALYs). This results in an incremental cost per QALY of £27?120 and an incremental cost per life year gained of £15?508. Results were similar with calcium acetate.

Conclusion: Together with the unique morbidity and mortality benefits, this study suggests that treatment with sevelamer confers clinical benefits with a modest investment of additional economic resources.     

The economic value of anti-IgE in severe persistent,IgE-mediated (allergic) asthma patients:adaptation of INNOVATE to Sweden

ABSTRACT

Background: Severe allergic asthma patients may not be controlled even with guideline recommended care, including inhaled corticosteroids, long-acting beta-2 agonists, theophylline, oral steroids and anti-leukotrienes. They experience exacerbations requiring intensive healthcare use and which may be fatal. Omalizumab, a new monoclonal antibody for use in IgE-mediated allergic diseases, reduces exacerbations and daily symptoms in this patient population. The aim of this study is to estimate the cost effectiveness of adding omalizumab to optimized standard therapy (ST) in patients with severe persistent IgE-mediated (allergic) asthma.

Methods: A Markov model comparing lifelong ST with a treatment period of omalizumab add-on therapy followed by ST, was developed based on efficacy data from the INNOVATE trial (28 weeks, N = 419) and Swedish life table and cost data. This model assumes that patients are at risk of having an exacerbation every 2 weeks and are at risk of dying from a clinically significant severe asthma exacerbation. Patients in a steady-state of having no exacerbations are defined to be in an ‘optimized asthma control’ state. Resource use data and utilities were obtained from INNOVATE and from a UK observational study. Costs from a societal perspective include estimates for drugs, routine care, exacerbations and costs in added years of life; benefits are expressed in QALYs. The response to omalizumab was evaluated after 16 weeks of trial, and non-responders stopped taking omalizumab for the remaining time.

Results: Total lifetime discounted costs and QALYs on ST were €52?702 and 11.60. Omalizumab add-on therapy cost an additional €42?754 for 0.76 additional QALYs, resulting in an incremental cost-effectiveness ratio of €56?091. A probabilistic sensitivity analysis indicates that the 95% CI around the ICER is [€31?328; €120?552]. One-way analyses indicate that the results are sensitive to the exacerbation-related mortality rate, the time horizon and the discount rates.

Conclusions: Based on the model and the assumptions used, our results suggest that omalizumab provides cost offsets, improves quality of life and may have an attractive ICER in treating the severe allergic asthma population.     

A cost-effectiveness analysis of calcipotriol plus betamethasone dipropionate aerosol foam versus gel for the topical treatment of plaque psoriasis

Background: Calcipotriol 50 µg/g and betamethasone 0.5?mg/g dipropionate (Cal/BD) aerosol foam formulation provides greater effectiveness and improved patient preference compared with traditional Cal/BD formulations for the topical treatment of plaque psoriasis.

Objective: To determine the cost-effectiveness of Cal/BD foam compared with Cal/BD gel from the Australian perspective.

Methods: A Markov model was developed to evaluate the cost-effectiveness of topical Cal/BD foam and gel for the treatment of people with plaque psoriasis. Treatment effectiveness, safety, and utilities were based on a randomized control trial, resource use was informed by expert opinion, and unit costs were obtained from public sources. Outcomes were reported in terms of 1-year costs, quality-adjusted life years, and incremental cost-effectiveness ratios. All costs were reported in 2017 Australian Dollars.

Results: The model showed that patients using Cal/BD foam had more QALYs and higher costs over 1 year compared with patients using Cal/BD gel, resulting in a cost of $13,609 per QALY gained at 4-weeks. When 4 weeks of Cal/BD foam was compared with 8 weeks of Cal/BD gel treatment, Cal/BD foam was $8 less expensive and resulted in 0.006 more QALYs gained. Sensitivity analyses showed that, compared with Cal/BD ointment, Cal/BD foam was associated with an incremental cost of $15,091 per QALY gained.

Conclusion: Cal/BD foam is the most cost-effective Cal/BD formulation for the topical treatment of patients with plaque psoriasis.     

JAK3-selective inhibitor peficitinib for the treatment of rheumatoid arthritis

Introduction: Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease characterized by synovitis as well as symmetric and destructive arthropathy. Although several disease modified antirheumatic-drugs (DMARDs) have widely used in clinical practice, certain patients are nonresponsive to or cannot take such medications due to adverse reactions. It is evident that Janus kinase (JAK) inhibitors have the potential to provide a significant breakthrough in the treatment of RA. These potent, orally administered, JAK inhibitors simplify the treatment options for patients.

Areas covered: We discuss the pharmacodynamics, pharmacokinetics, efficacy, and safety of peficitinib for the treatment of RA.

Expert opinion: Peficitinib is a novel JAK3 inhibitor potently inhibiting JAK3 enzymatic activity and JAK1/3-mediated cell proliferation. Its selectivity for JAK family kinases is similar to that of tofacitinib, but slightly less potent for JAK2. It is currently being evaluated by the FDA to treat adult patients with moderately to severely active RA who show inadequate response to or are intolerant of methotrexate. It can be used either as monotherapy or combination therapy with methotrexate, or other DMARDs. However, we think that more cautious consideration and measurement for adverse events are needed, after considering the safety results of ongoing clinical studies of peficitinib.     

Cost-effectiveness analysis of a multivariate index assay compared to modified American College of Obstetricians and Gynecologists criteria and CA-125 in the triage of women with adnexal masses

Objective:

To evaluate the cost-effectiveness of the multivariate index assay (MIA) for use in triaging women with an adnexal mass relative to modified American College of Obstetricians and Gynecologists (mACOG) referral guidelines and CA-125 testing alone.

Methods:

The MIA triage algorithm was based on qualitative serum testing of five biomarkers: transthyretin, apolipoprotein, A-1, 2-microglobulin, transferrin, and CA-125. An economic analysis was developed to evaluate the clinical and cost implications of adopting MIA in clinical practice versus the mACOG referral guidelines and CA-125 alone, over a lifetime horizon, from the perspective of the public payer. Clinical parameters used to characterize patients’ disease status, quality of life, and treatment decisions were estimated using the results of published studies; costs were approximated using reimbursement rates from CMS fee schedules. Model endpoints included overall survival (OS), costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). The cost-effectiveness threshold was set to $50,000 per QALY. One-way sensitivity analysis was performed to assess uncertainty of individual parameters included in the analysis. All costs were reported in 2014 US dollars.

Results:

Use of MIA was cost-effective, resulting in fewer re-operations and pre-treatment CT scans. Overall MIA resulted in an ICER of $35,094/QALY gained. MIA was also cost-saving and QALY-increasing compared to use of CA-125 alone with an ICER of $12,189/QALY gained. One-way sensitivity analysis showed the ICER was most affected by the following parameters: (1) sensitivity of MIA; (2) sensitivity of mACOG; and (3) percentage of patients, not referred to a gynecologic oncologist, who were correctly diagnosed with advanced epithelial ovarian cancer (EOC).

Conclusion:

Use of MIA is a more cost-effective triage strategy than mACOG or CA-125. It is expected to increase the percentage of women with ovarian cancer that are referred to gynecologic oncologists, which is shown to improve clinical outcomes. Limitations include the use of assumptions when published data was unavailable, and the use of multiple sources for survival data.     

Economic evaluation of major knee surgery with recombinant activated factor VII in hemophilia patients with high titer inhibitors and advanced knee arthropathy: exploratory results via literature-based modeling

ABSTRACT

Objectives: People with severe hemophilia suffer from frequent intra-articular hemorrhages, leading to pain, swelling, reduced flexion, and arthropathy. Elective orthopedic surgery using factor VIII (FVIII) replacement to prevent uncontrolled bleeding has been endorsed as an effective treatment option for patients with severe or advanced hemophilic arthropathy. These surgeries reduce pain, restore mobility and function, and reduce the frequency of recurrent joint bleeds. Unfortunately, some patients with hemophilia develop inhibitors to FVIII, which neutralize FVIII activity and render the use of even massive amounts of FVIII replacement ineffective and surgery very risky. For this reason, elective surgical procedures in high-titer inhibitor patients had largely been abandoned until the introduction of new agents, such as recombinant activated factor VII (rFVIIa, NovoSeven, Novo Nordisk A/S, Denmark). rFVIIa has been shown effective for prophylaxis during elective surgery and has therefore improved the feasibility of orthopedic surgery in hemophilia patients with high-titer inhibitors. The present research explored, from a modified US payer perspective, the direct economic and quality of life benefits of four different elective knee surgeries (total knee replacement [TKR], knee arthrodesis [KA], proximal tibial osteotomy, and distal femoral osteotomy) with rFVIIa coverage in hemophilia patients with high-titer inhibitors.

Methods: An exploratory literature-based life-table model was developed to compare the direct medical costs and quality of life of two hypothetical cohorts of high-titer inhibitor patients with frequent bleeding episodes: one undergoing and the other not undergoing elective knee surgery. Knee surgery costs included perioperative rFVIIa costs, inpatient and rehabilitation care, and repeat procedures due to surgery failure, prosthesis loosening or deep infection. Based on efficacy studies, knee surgery was assumed to reduce mean annual bleeding episodes at the affected joint from 9.13 to 1.64. The cost of managing each bleeding episode was estimated at $15?298. Thus, by reducing bleeding episodes, surgery was expected to result in related cost offsets. All costs were expressed in 2006 US dollars. Surgery was also assumed to result in gains in quality of life by reducing pain and reducing bleeding episodes. The impact of pain reduction on quality of life and utility was estimated by simulating EQ-5D scores for a typical patient with and without knee surgery.

Results: Based on the model, average knee surgery costs are predicted to range from a low of $694?000 (for KA) to a high of $855?000 (for TKR). However, knee surgery is also expected to reduce the subsequent number of bleeding episodes and resultant costs, leading to long-term costs savings. Due to improvement in pain levels, surgical patients are expected to experience improvements in quality-adjusted life-years (QALYs). Thus, surgery appears to be the preferred strategy (i.e., saves costs and increases QALYs). Based on the assumptions used in the model, the initial cost of knee surgery was offset during the 8th and 10th years for KA and TKR, respectively, with intermediate break-even time for the other surgeries. As expected, cost savings and gains in QALYs increased over time, as well as the cost effective­ness of knee surgery. Specifically, the cost per QALY with KA and TKR fell under $50?000/QALY during the 6th and 8th years, respectively, with intermediate time for the other surgeries.

Conclusions: The present exploratory analysis is based on the long-term extrapolation of data from a small number of patients without inhibitors and short-term studies. It suggests that major knee surgery utilizing rFVIIa in hemophilia patients with inhibitors may be cost-effective on average, with expected cost savings apparent within a decade of knee surgery. The present exploratory results should be validated with real-world, longitudinal patient data.     

Cost-effectiveness of insulin aspart versus human soluble insulin in type 2 diabetes in four European countries: subgroup analyses from the PREDICTIVE study

ABSTRACT

Objectives: To evaluate the long-term health economic outcomes associated with insulin aspart (IAsp) compared to human soluble insulin (HI) in type 2 diabetes patients on basal-bolus therapy in Sweden, Spain, Italy and Poland.

Methods: A published computer simulation model of diabetes was used to predict life expectancy, quality-adjusted life expectancy and incidence of diabetes-related complications. Baseline cohort characteristics (age 61.6 years, duration of diabetes 13.2 years, 45.1% male, HbA_1c 8.2%, BMI 29.8?kg/m²) and treatment effects were derived from the PREDICTIVE observational study. Country-specific complication costs were derived from published sources. The analyses were run over 35-year time horizons from third-party payer perspectives in Spain, Italy and Poland and from a societal perspective in Sweden. Future costs and clinical benefits were discounted at country-specific discount rates. Sensitivity analyses were performed.

Results: IAsp was associated with improvements in discounted life expectancy and quality-adjusted life expectancy, and a reduced incidence of most diabetes-related complications versus HI in all four settings. IAsp was associated with societal cost-savings in Sweden (SEK 2470), direct medical cost-savings in Sweden and Spain (SEK 8248 and €1382, respectively), but increased direct costs in Italy (€2235) and Poland (€743). IAsp was associated with improved quality-adjusted life expectancy in Sweden (0.077 QALYs), Spain (0.080 QALYs), Italy (0.120 QALYs) and Poland (0.003 QALYs).

Conclusions: IAsp was dominant versus HI in both Sweden and Spain, would be considered cost-effective in Italy with an incremental cost-effectiveness ratio of €18?597 per QALY gained, but would not be considered cost-effective in Poland.     

Improved perioperative blood pressure control leads to reduced hospital costs

Background: Perioperative hypertension affects 80% of cardiac surgery patients and is associated with an increased risk of complications.

Objective: To determine the relationship between perioperative blood pressure (BP) control and hospital costs for cardiac surgery in the United States (US) and estimate the potential cost reductions associated with effective therapies.

Methods: The analysis estimated hospitalization costs (2011 US dollars (USD)) for cardiac surgery when BP was controlled with intravenous (IV) antihypertensives. Patient characteristics, hospital length of stay, and clinical event rates during the initial hospitalization and post-discharge 30 days after study drug infusion were based on the ECLIPSE (Evaluation of CLevidipine In the Perioperative Treatment of Hypertension Assessing Safety Events) trials. These clinical trial data were combined with data from the Massachusetts Acute Hospital Case Mix Database 2007 – 2009 (MA Case Mix Database) to estimate total hospitalization costs.

Results: Effective perioperative BP control in patients requiring IV antihypertensives was associated with a 7% decrease in hospital costs compared with less effective BP control. Reductions in total hospital costs associated with clevidipine versus other IV antihypertensives averaged $394 per patient overall. Cost savings with clevidipine exceeded $500 per patient versus sodium nitroprusside and nitroglycerin, but only $22 compared to nicardipine.

Conclusion: Improved perioperative BP control may reduce hospital costs. Given the low cost of IV antihypertensives, the total hospital cost reductions may offset any incremental cost increases associated with newer, more effective therapies.     

Budget impact of treating commercially insured type 1 and type 2 diabetes patients in the United States with insulin degludec compared to insulin glargine

Objective: To quantify the annual budget impact if all US commercially insured type 1 diabetes mellitus patients on basal–bolus therapy (T1DM_BBT), type 2 diabetes mellitus patients on basal–oral therapy (T2DM_BOT), and type 2 diabetes mellitus patients on basal–bolus therapy (T2DM_BBT) switched from insulin glargine (IGlar) to insulin degludec (IDeg).

Methods: A short-term (1 year) budget impact model was developed to evaluate the costs of IDeg vs. IGlar in three treatment groups (T1DM_BBT, insulin-naïve T2DM_BOT, and T2DM_BBT) through a simulation for a potential US health plan population of 35 million. The analysis captured direct medical costs associated with insulin treatment (insulin, needles, and self-monitored glucose testing) and costs related to managing hypoglycemic episodes. There were a total of 59,780 T1DM_BBT patients, 383,145 T2DM_BOT patients, and 171,325 T2DM_BBT patients expected to be using long-acting insulin. A sensitivity analysis on the entire US population was also conducted.

Results: Among T1DM_BBT patients, IDeg was associated with an annual cost savings of ?$357.13 per patient per year (PPPY), driven primarily by reduced insulin utilization. IDeg was also found to be cost saving among T2DM_BOT patients (?$1206.61 PPPY), driven primarily by reductions in the cost of treating severe hypoglycemic episodes. Among T2DM_BBT patients, IDeg was associated with an additional cost to the plan of $1420.04 PPPY; however, this result was driven by a higher insulin dose for IDeg compared to IGlar. Overall, IDeg demonstrated cost savings of $240 million per year, which accounted for total cost savings of 3.5% vs. IGlar.

Conclusions: The results of this analysis suggest that the reduced insulin utilization and fewer hypoglycemic episodes associated with IDeg may translate into reduced costs for payers. The model is limited by simplification of a complex disease state and assumptions surrounding disease state, treatment patterns, and costs. Therefore, results may not accurately reflect actual health plans or real-world practice patterns.