Economic evaluation of ezetimibe treatment in combination with statin therapy in the United States

Aims: This study assessed the cost-effectiveness of ezetimibe with statin therapy vs statin monotherapy from a US payer perspective, assuming the impending patent expiration of ezetimibe.

Methods: A Markov-like economic model consisting of 28 distinct health states was used. Model population data were obtained from US linked claims and electronic medical records, with inclusion criteria based on diagnostic guidelines. Inputs came from recent clinical trials, meta-analyses, and cost-effectiveness analyses. The base-case scenario was used to evaluate the cost-effectiveness of adding ezetimibe 10?mg to statin in patients aged 35–74 years with a history of coronary heart disease (CHD) and/or stroke, and with low-density lipoprotein cholesterol (LDL-C) levels ≥70?mg/dL over a lifetime horizon, assuming a 90% price reduction of ezetimibe after 1 year to take into account the impending patent expiration in the second quarter of 2017. Sub-group analyses included patients with LDL-C levels ≥100?mg/dL and patients with diabetes with LDL-C levels ≥70?mg/dL.

Results: The lifetime discounted incremental cost-effectiveness ratio (ICER) for ezetimibe added to statin was $9,149 per quality-adjusted life year (QALY) for the base-case scenario. For patients with LDL-C levels ≥100?mg/dL, the ICER was $839/QALY; for those with diabetes and LDL-C levels ≥70?mg/dL, it was $560/QALY. One-way sensitivity analyses showed that the model was sensitive to changes in cost of ezetimibe, rate reduction of non-fatal CHD, and utility weight for non-fatal CHD in the base-case and sub-group analyses.

Limitations: Indirect costs or treatment discontinuation estimation were not included.

Conclusions: Compared with statin monotherapy, ezetimibe with statin therapy was cost-effective for secondary prevention of CHD and stroke and for primary prevention of these conditions in patients whose LDL-C levels are ≥100?mg/dL and in patients with diabetes, taking into account a 90% cost reduction for ezetimibe.     

Cost-effectiveness of droxidopa in patients with neurogenic orthostatic hypotension: post-hoc economic analysis of Phase 3 clinical trial data

Objective:

Falls are associated with neurogenic orthostatic hypotension (nOH) and are an economic burden on the US healthcare system. Droxidopa is approved by the US FDA to treat symptomatic nOH. This study estimates the cost-effectiveness of droxidopa vs standard of care from a US payer perspective.

Methods:

A Markov model was used to predict numbers of falls and treatment responses using data from a randomized, double-blind trial of patients with Parkinson’s disease and nOH who received optimized droxidopa therapy or placebo for 8 weeks. The severity of falls, utility values, and injury-related costs were derived from published studies. Model outcomes included number of falls, number of quality-adjusted life-years (QALYs), and direct costs. Incremental cost-effectiveness ratios (ICERs) were calculated. Outcomes were extrapolated over 12 months.

Results:

Patients receiving droxidopa had fewer falls compared with those receiving standard of care and gained 0.33 QALYs/patient. Estimated droxidopa costs were $30,112, with estimated cost savings resulting from fall avoidance of $14,574 over 12 months. Droxidopa was cost-effective vs standard of care, with ICERs of $47,001/QALY gained, $24,866 per avoided fall with moderate/major injury, and $1559 per avoided fall with no/minor injury. The main drivers were fall probabilities and fear of fall-related inputs.

Limitations:

A limitation of the current study is the reliance on falls data from a randomized controlled trial where the placebo group served as the proxy for standard of care. Data from a larger patient population, reflecting ‘real-life’ patient use and/or comparison with other agents used to treat nOH, would have been a useful complement, but these data were not available.

Conclusion:

Using Markov modeling, droxidopa appears to be a cost-effective option compared with standard of care in US clinical practice for the treatment of nOH.     

Cost-effectiveness of percutaneous closure of a patent foramen ovale compared with medical management in patients with a cryptogenic stroke: from the US payer perspective

Abstract

Aims: To evaluate the cost-effectiveness of percutaneous patent foramen ovale (PFO) closure, from a US payer perspective. Lower rates of recurrent ischemic stroke have been documented following percutaneous PFO closure in properly selected patients. Stroke in patients aged <60?years is particularly interesting because this population is typically at peak economic productivity and vulnerable to prolonged disability.

Materials and methods: A Markov model comprising six health states (Stable after index stroke, Transient ischemic attack, Post-Transient Ischemic Attack, Clinical ischemic stroke, Post-clinical ischemic stroke, and Death) was constructed to evaluate the cost-effectiveness of PFO closure in combination with medical management versus medical management alone. The base-case model employed a 5-year time-horizon, with transition probabilities, clinical inputs, costs, and utility values ascertained from published and national costing sources. Incremental cost-effectiveness ratio (ICER) was evaluated per US guidelines, utilizing a discount rate of 3.0%.

Results: At 5?years, overall costs and quality-adjusted life-years (QALYs) obtained from PFO closure compared with medical management were $16,323 vs $7,670 and 4.18 vs 3.77, respectively. At 5?years, PFO closure achieved an ICER of $21,049, beneficially lower than the conventional threshold of $50,000. PFO closure reached cost-effectiveness at 2.3?years (ICER = $47,145). Applying discount rates of 0% and 6% had a negligible impact on base-case model findings. Furthermore, PFO closure was 95.4% likely to be cost-effective, with a willingness-to-pay (WTP) threshold of $50,000 and a 5-year time horizon.

Limitations: From a cost perspective, our economic model employed a US patient sub-population, so cost data may not extrapolate to other non-US stroke populations.

Conclusion: Percutaneous PFO closure plus medical management represents a cost-effective approach for lowering the risk of recurrent stroke compared with medical management alone.     

Cost effectiveness of rosuvastatin in patients at risk of cardiovascular disease based on findings from the JUPITER trial

Abstract

Objective:

This study assessed the long-term cost effectiveness of rosuvastatin therapy compared with placebo in reducing the incidence of major cardiovascular (CVD) events and mortality.

Methods:

A probabilistic Monte Carlo simulation model estimated long-term cost effectiveness of rosuvastatin therapy (20?mg daily) for the prevention of CVD mortality and morbidity. The model included three stages: (1) CVD prevention simulating the 4 years of the JUPITER trial, (2) initial CVD prevention beyond the trial, and (3) subsequent CVD event prevention. A US payer perspective was assessed reflecting direct medical costs, and up to a lifetime horizon. Sensitivity analyses tested the robustness of the model estimates.

Results:

For a hypothetical cohort of 100,000 patients at moderate and high risk of CVD events based on Framingham risk of ≥10%, estimated quality-adjusted life-years (QALYs) gained with rosuvastatin therapy compared with placebo was 33,480 over a lifetime horizon, and 25,380 and 9916 over 20-year and 10-year horizons, respectively. Approximately 12,073 events were avoided over the lifetime; 6,146 non-fatal MIs, 2905 non-fatal strokes, and 4030 CVD deaths avoided. Estimated incremental cost-effectiveness ratio (ICER) for cost per QALY was $7062 (lifetime), $10,743 (20-year horizon), and $44,466 (10-year horizon). For a hypothetical cohort similar to the overall JUPITER population, the cost per QALY ICER was $11,025 for the lifetime and $60,112 for a 10-year horizon.

Limitations:

The cost-effectiveness comparison of rosuvastatin 20?mg was against no active treatment (as opposed to an alternative statin) due to lack of comparative cardiovascular morbidity and mortality risk reduction data for other statins in a population similar to the JUPITER trial population. The analysis was conducted from the payer perspective and lack of inclusion of indirect costs limit interpretability of results from a societal perspective.

Conclusions:

Treatment with rosuvastatin 20?mg daily, is a cost-effective treatment alternative to no treatment in patients at a higher risk (Framingham risk ≥10%) of CVD.     

Cost-effectiveness of ceritinib in previously untreated anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer in the United States

Aims: To assess the cost-effectiveness of first-line ceritinib vs crizotinib and platinum doublet chemotherapy for anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) from a US third-party payer’s perspective.

Materials and methods: A partitioned survival model with three health states (stable disease, progressive disease, death) was developed over a 20-year time horizon. Ceritinib’s efficacy inputs (progression-free and overall survival) were estimated from ASCEND-4; parametric survival models extrapolated data beyond the trial period. The relative efficacy of ceritinib vs chemotherapy was obtained from ASCEND-4, the relative efficacy of ceritinib vs crizotinib was estimated using a matching-adjusted indirect comparison based on ASCEND-4 and PROFILE 1014. Drug acquisition, treatment administration, adverse event management, and medical costs were obtained from publicly available databases and the literature, and inflated to 2016?US dollars. Treatment-specific stable-state utilities were derived from trials and progressive-state utility from the literature. Incremental costs per quality-adjusted life year (QALY) were estimated for ceritinib vs each comparator. Cost-effectiveness was assessed based on US willingness-to-pay thresholds. Deterministic and probabilistic sensitivity analyses were performed to test model robustness.

Results: In the base case, first-line ceritinib was associated with total direct costs of $299,777 and 3.28 QALYs (from 4.61 life years gained [LYG]) over 20 years. First-line crizotinib and chemotherapy were associated with 2.73 and 2.41 QALYs, 3.92 and 3.53 LYG, and $263,172 and $228,184 total direct costs, respectively. The incremental cost per QALY gained was $66,064 for ceritinib vs crizotinib and $81,645 for ceritinib vs chemotherapy. In the first 2 years following treatment initiation, ceritinib dominated crizotinib by conferring greater health benefits at reduced total costs. Results were robust to deterministic and probabilistic sensitivity analyses.

Limitations: In the absence of head-to-head trials, an indirect comparison method was used.

Conclusions: Ceritinib is cost-effective compared to crizotinib and chemotherapy in the treatment of previously untreated ALK-positive metastatic NCSLC in the US.     

Cost-effectiveness analysis of roflumilast/tiotropium therapy versus tiotropium monotherapy for treating severe-to-very severe COPD

Abstract

Objective:

To conduct a cost-effectiveness analysis comparing roflumilast/tiotropium therapy vs tiotropium monotherapy in patients with severe-to-very severe COPD.

Methods:

The economic evaluation applied a disease-based Markov cohort model with five health states: (1) severe COPD, (2) severe COPD with a history of severe exacerbation, (3) very severe COPD, (4) very severe COPD with a history of severe exacerbation, and (5) death. Within a given health state, a patient may have a mild/moderate or severe exacerbation or die. Data from roflumilast clinical trials and published literature were used to populate model parameters. The model calculated health outcomes and costs for roflumilast/tiotropium therapy vs tiotropium monotherapy over a 5-year horizon. Incremental cost and benefits were then calculated as cost-effectiveness ratios, including cost per exacerbation avoided and cost per quality adjusted life year ($/QALY).

Results:

Over a 5-year horizon, the estimated incremental costs per exacerbation and per severe exacerbation avoided were $589 and $5869, respectively, and the incremental cost per QALY was $15,815. One-way sensitivity analyses varying key parameters produced an incremental cost per QALY ranging from $1963–$32,773.

Limitations:

A number of key parameters used in the model were obtained from studies in the literature that were conducted under different contexts. Specifically, the relative risk estimate for severe COPD patients originates from a small trial not designed to demonstrate the impact of roflumilast on frequency of exacerbations. In addition, the model extrapolates the relative risk estimates over periods of 5–30 years, even though the estimates were only observed in trials that spanned less than a year.

Conclusions:

The addition of roflumilast to tiotropium is cost-effective for the treatment of severe to very severe COPD patients.     

Cost-effectiveness of delayed-release dimethyl fumarate for the treatment of relapsing forms of multiple sclerosis in the United States

Objective:

To assess the cost-effectiveness of delayed-release dimethyl fumarate (DMF, also known as gastro-resistant DMF), an effective therapy for relapsing forms of multiple sclerosis (MS), compared with glatiramer acetate and fingolimod, commonly used treatments in the US.

Methods:

A Markov model was developed comparing delayed-release DMF to glatiramer acetate and fingolimod using a US payer perspective and 20-year time horizon. A cohort of patients, mean age 38 years, with relapsing-remitting MS and Kurtzke Expanded Disability Status Scale (EDSS) scores between 0–6 entered the model. Efficacy and safety were estimated by mixed-treatment comparison of data from the DEFINE and CONFIRM trials and clinical trials of other disease-modifying therapies. Data from published studies were used to derive resource use, cost, and utility inputs. Key outcomes included costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Alternative scenarios tested in a sensitivity analysis included drug efficacy, EDSS-related or relapse-related costs, alternative perspectives, drug acquisition costs, and utility.

Results:

Base-case results with a 20-year time horizon indicated that delayed-release DMF increased QALYs +0.450 or +0.359 compared with glatiramer acetate or fingolimod, respectively. Reductions in 20-year costs with delayed-release DMF were ?$70,644 compared with once-daily glatiramer acetate and ?$32,958 compared with fingolimod. In an analysis comparing delayed-release DMF to three-times-weekly glatiramer acetate and assuming similar efficacy and safety to the once-daily formulation, 20-year costs with delayed-release DMF were increased by $15,806 and cost per QALY gained was $35,142. The differences in costs were most sensitive to acquisition cost and inclusion of informal care costs and productivity losses. The differences in QALYs were most sensitive to the impact of delayed-release DMF on disease progression and the EDSS utility weights.

Conclusion:

Delayed-release DMF is likely to increase QALYs for patients with relapsing forms of MS and be cost-effective compared with fingolimod and glatiramer acetate.     

Cost-effectiveness of ranibizumab and aflibercept to treat diabetic macular edema from a US perspective: analysis of 2-year Protocol T data

Abstract

Aims: Protocol T (NCT01627249) was a head-to-head study conducted by the Diabetic Retinopathy Clinical Research Network that compared intravitreal aflibercept, bevacizumab, and ranibizumab for the treatment of diabetic macular edema (DME). A cost-effectiveness analysis accompanying the 1-year data of Protocol T revealed that aflibercept was not cost-effective vs ranibizumab for all patients, but could have been cost-effective in certain patient sub-groups if the 1-year results were extrapolated out to 10?years. The present study evaluated the cost-effectiveness of US Food and Drug Administration-approved anti-vascular endothelial growth factor agents (ranibizumab, aflibercept) for treatment of DME using the 2-year data from Protocol T.

Methods: Costs of aflibercept 2.0?mg or ranibizumab 0.3?mg, visual acuity (VA)-related medical costs, and quality-adjusted life-years (QALYs) were simulated for eight VA health states. Treatment, adverse event management, and VA-related healthcare resource costs (2016 US dollars) were based on Medicare reimbursement and published literature. VA-related health utilities were determined using a published algorithm. Patients were stratified by baseline VA: 20/40 or better; 20/50 or worse.

Results: Total 2-year costs were higher, and QALYs similar, for aflibercept vs ranibizumab in the full cohort ($44,423 vs $34,529; 1.476 vs 1.466), 20/40 or better VA sub-group ($40,854 vs $31,897; 1.517 vs 1.519), and 20/50 or worse VA sub-group ($48,214 vs $37,246; 1.433 vs 1.412), respectively. Incremental cost-effectiveness ratios in the full cohort and 20/50 or worse VA sub-group were $986,159/QALY and $523,377/QALY, respectively. These decreased to $711,301 and $246,978 when analyses were extrapolated to 10?years.

Limitations: Key potential limitations include the fact that VA was the only QALY parameter analyzed and the uncertainty surrounding the role of better- and worse-seeing eye VA in overall functional impairment.

Conclusions: This analysis suggests that aflibercept is not cost-effective vs ranibizumab for patients with DME, regardless of baseline vision.     

Long-term cost-effectiveness analysis shows that IDegLira is associated with improved outcomes and lower costs compared with insulin glargine U100 plus insulin aspart in the US

Abstract

Aims: The clinical and economic impact of diabetes is growing in the US. Choosing therapies that are both effective and cost-effective is becoming increasingly important. The aim of the present analysis was to assess the long-term cost-effectiveness of IDegLira for treatment of patients with type 2 diabetes mellitus not meeting glycemic targets on basal insulin, vs insulin glargine U100 plus insulin aspart, in the US setting.

Materials and methods: Long-term projections of cost-effectiveness outcomes were made using the IQVIA CORE Diabetes Model. Clinical inputs were based on the DUAL VII trial, with costs (accounted from a healthcare payer perspective) and utilities based on published sources. Future costs and clinical benefits were discounted at 3% annually.

Results: IDegLira was associated with increased discounted life expectancy by 0.02 years and increased discounted quality-adjusted life expectancy by 0.22 quality-adjusted life years compared with insulin glargine U100 plus insulin aspart. Evaluation of direct medical costs suggested that the mean cost per patient with IDegLira was $3,571 lower than with insulin glargine U100 plus insulin aspart. The cost saving was driven predominantly by the lower acquisition cost of IDegLira compared with insulin glargine U100 plus insulin aspart, with further cost savings identified as a result of avoided treatment of diabetes-related complications. IDegLira was associated with improved clinical outcomes at a reduced cost compared with insulin glargine U100 plus insulin aspart.

Conclusions: Based on clinical trial data, the present analysis suggests that IDegLira is associated with improved clinical outcomes and cost savings compared with treatment with insulin glargine U100 plus insulin aspart for patients with type 2 diabetes not achieving glycemic control on basal insulin in the US. Therefore, IDegLira is likely to be considered dominant (cost saving and more effective) and, consequently, highly cost-effective in the US setting.     

Pharmacoeconomic analysis of paricalcitol and calcitriol in the treatment of secondary hyperparathyroidism in haemodialysis: impact of hospitalisations and survival

Summary

The objective of this study was to evaluate the cost effectiveness of paricalcitol injection compared with calcitriol injection when used to reduce parathyroid hormone levels in patients undergoing haemodialysis. A decision tree was developed to model the 1-year costs and outcomes of therapy for secondary hyperparathyroidism from a US government payer's perspective (2005 US$). Probabilities of hospitalisations and survival with paricalcitol and calcitriol were obtained from published observational studies.

When only drug costs and survival were considered, the incremental cost effectiveness of paricalcitol over calcitriol was $9,900 per life saved. When utilities were included, the incremental cost-effectiveness ratio for paricalcitol compared with calcitriol was $13,200 per quality-adjusted life year. When both drug and hospitalisation costs were included in a cost analysis, paricalcitol treatment was cost saving compared with calcitriol, and when hospitalisation costs were included in both the cost-effectiveness analysis and cost-utility analysis paricalcitol demonstrated first-order dominance, cost savings and cost effectiveness.

This decision analysis demonstrated that paricalcitol injection is both cost effective and cost saving compared with calcitriol injection.     

Cost-effectiveness analysis of second-line tyrosine kinase inhibitor treatment for chronic myelogenous leukemia

Aim:

A cost-effectiveness analysis was performed for sequential treatments of chronic myelogenous leukemia (CML) with tyrosine kinase inhibitors (TKIs) after failure of 1st line imatinib, from a commercial payer perspective in the US.

Methods:

A Markov model was developed to simulate lifetime treatment costs and health outcomes for TKI sequences for treatment of patients resistant or intolerant to 1st-line imatinib. Five health states were included, chronic phase 2nd-line TKI, chronic phase 3rd-line TKI, chronic phase post-TKI, advanced phases, and death. Efficacy (response achievement, loss of response, transformation, death) and safety (adverse events incidence, discontinuation) data are based on clinical trials. Resource utilization, costs, and utilities were based on product labels and publically available data. Uncertainty analyses were conducted for key inputs.

Results:

In patients failing imatinib, dasatinib-initiating treatment sequences provide the most survival (ΔLYs?=?0.2–2.0), QALYs (ΔQALYs?=?0.2–1.9), and accrue highest CML-related costs (ΔCosts?=?$64,000–$222,000). The average ICER per QALY for dasatinib- vs imatinib-initiating sequences is $100,000 for an imatinib-resistant population. The average ICER per QALY for dasatinib- vs nilotinib-initiating sequences is $170,000 for an imatinib-resistant population, and $160,000 for an imatinib-intolerant population.

Conclusions:

This analysis suggests that dasatinib is associated with increased survival and quality of life compared to high dose imatinib and to a smaller extent with nilotinib, among patients resistant or intolerant to 1st-line imatinib, primarily based on higher cytogenetic response rates observed in clinical studies of dasatinib. Head-to-head studies of sequential use of dasatinib and nilotinib are needed to validate the model findings of improved survival (LYs) with better quality-of-life (QALYs) for patients initiating dasatinib in 2nd-line. However, the model findings (in light of higher cytogenetic response rates with dasatinib) are supported by other studies showing improved quality-of-life for responders, and improved survival for patients achieving cytogenetic response.     

Cost-effectiveness of subdermal implantable buprenorphine versus sublingual buprenorphine to treat opioid use disorder

Aims: Subdermal implantable buprenorphine (BSI) was recently approved to treat opioid use disorder (OUD) in clinically-stable adults. In the pivotal clinical trial, BSI was associated with a higher proportion of completely-abstinent patients (85.7% vs 71.9%; p?=?.03) vs sublingual buprenorphine (SL-BPN). Elsewhere, relapse to illicit drug use is associated with diminished treatment outcomes and increased costs. This study evaluated the cost-effectiveness of BSI vs SL-BPN from a US societal perspective.

Methods: A Markov model simulated BSI and SL-BPN cohorts (clinically-stable adults) transiting through four mutually-exclusive health states for 12 months. Cohorts accumulated direct medical costs from drug acquisition/administration; treatment-diversion/abuse; newly-acquired hepatitis-C; emergency room, hospital, and rehabilitation services; and pediatric poisonings. Non-medical costs of criminality, lost wages/work-productivity, and out-of-pocket expenses were also included. Transition probabilities to a relapsed state were derived from the aforementioned trial. Other transition probabilities, costs, and health-state utilities were derived from observational studies and adjusted for trial characteristics. Outcomes included incremental cost per quality-adjusted-life-year (QALY) gained and incremental net-monetary-benefit (INMB). Uncertainty was assessed by univariate and probabilistic sensitivity analysis (PSA).

Results: BSI was associated with lower total costs (?$4,386), more QALYs (+0.031), and favorable INMB at all willingness-to-pay (WTP) thresholds considered. Higher drug acquisition costs for BSI (+$6,492) were outpaced, primarily by reductions in emergency room/hospital utilization (?$8,040) and criminality (?$1,212). BSI was cost-effective in 89% of PSA model replicates, and had a significantly higher NMB at $50,000/QALY ($20,783 vs $15,007; p?Conclusions: BSI was preferred over SL-BPN from a health-economic perspective for treatment of OUD in clinically-stable adults. These findings should be interpreted carefully, due to some relationships having been modeled from inputs derived from multiple sources, and would benefit from comparison with outcomes from studies that employ administrative claims data or a naturalistic comparative design.     

Cost-effectiveness of renal denervation therapy for the treatment of resistant hypertension in The Netherlands

Abstract

Objectives:

Safety and efficacy data for catheter-based renal denervation (RDN) in the treatment of resistant hypertension have been used to estimate the cost-effectiveness of this approach. However, there are no Dutch-specific analyses. This study examined the cost-effectiveness of RDN from the perspective of the healthcare payer in The Netherlands.

Methods:

A previously constructed Markov state-transition model was adapted and updated with costs and utilities relevant to the Dutch setting. The cost-effectiveness of RDN was compared with standard of care (SoC) for patients with resistant hypertension. The efficacy of RDN treatment was modeled as a reduction in the risk of cardiovascular events associated with a lower systolic blood pressure (SBP).

Results:

Treatment with RDN compared to SoC gave an incremental quality-adjusted life year (QALY) gain of 0.89 at an additional cost of €1315 over a patient’s lifetime, resulting in a base case incremental cost-effectiveness ratio (ICER) of €1474. Deterministic and probabilistic sensitivity analyses (PSA) showed that treatment with RDN therapy was cost-effective at conventional willingness-to-pay thresholds (€10,000–80,000/QALY).

Conclusion:

RDN is a cost-effective intervention for patients with resistant hypertension in The Netherlands.     

The cost implications of the use of telmisartan or ramipril in patients at high risk for vascular events: the ONTARGET study

Abstract

Background:

The recently published ONTARGET trial found that telmisartan was non-inferior to ramipril in reducing CV death, MI, stroke, or heart failure in patients with vascular disease or high-risk diabetes. The cost implications of ramipril and telmisartan monotherapy use based on the ONTARGET study are reported here.

Methods and Results:

Only healthcare system costs were considered. Healthcare resource utilization was collected for each patient during the trial. The authors obtained country-specific unit costs to the different healthcare care resources consumed (i.e., hospitalizations events, procedures, non-study, and study drugs) for all enrolled patients. Purchasing power parities were used to convert country-specific costs into US dollars (US$ 2008). The total undiscounted costs of the study for the telmisartan group was $12,762 per patient and is higher than the ramipril group at $12,007 per patient, an un-discounted difference of $755 (95% confidence interval [CI], $218–$1292); The discounted costs for the telmisartan group was $11,722 compared with $11,019 for the ramipril group; a difference of $703 (95% CI, $209–$1197). The difference in costs is exclusively related to the acquisition cost of telmisartan over generic ramipril.

Limitations:

This analysis only considered direct healthcare system costs. Costs accrued outside the hospital were not collected. Combination therapy was excluded since it would likely be more expensive than ramipril alone, with no additional benefit and a risk of some harm.

Conclusions:

Based on these results, it is suggested that for the ONTARGET patients, the use of telmisartan instead of ramipril increases costs by 6.3%. These findings suggest that the choice to put patients on telmisartan should be justified based on the patient’s susceptibility to specific adverse events to minimize the cost implications.     

Febuxostat in the management of gout: a cost-effectiveness analysis

Objective:

To determine the cost-effectiveness of febuxostat vs allopurinol for the management of gout.

Methods:

A stochastic microsimulation cost-effectiveness model with a US private-payer perspective and 5-year time horizon was developed. Model flow based on guideline and real-world treatment paradigms incorporated gout flare, serum uric acid (sUA) testing, treatment titration, discontinuation, and adverse events, chronic kidney disease (CKD) incidence and progression, and type 2 diabetes mellitus (T2DM) incidence. Outcomes were estimated for the general gout population and for gout patients with CKD stages 3/4. Modeled treatment interventions were daily oral febuxostat 40–80?mg and allopurinol 100–300?mg. Baseline patient characteristics were taken from epidemiologic studies, efficacy data from randomized controlled trials, adverse event rates from package inserts, and costs from the literature, government sources, and expert opinion. Eight clinically-relevant incremental cost-effectiveness ratios were estimated: per patient reaching target sUA, per flare avoided, per CKD incidence, progression, stages 3/4 progression, and stage 5 progression avoided, per incident T2DM avoided, and per death avoided.

Results:

Five-year incremental cost-effectiveness ratios for the general gout population were $5377 per patient reaching target sUA, $1773 per flare avoided, $221,795 per incident CKD avoided, $29,063 per CKD progression avoided, $36,018 per progression to CKD 3/4 avoided, $71,426 per progression to CKD 5 avoided, $214,277 per incident T2DM avoided, and $217,971 per death avoided. In patients with CKD 3/4, febuxostat dominated allopurinol for all cost-effectiveness outcome measures.

Conclusions:

Febuxostat may be a cost-effective alternative to allopurinol, especially for patients with CKD stages 3 or 4.     

Cost-effectiveness of pembrolizumab in combination with chemotherapy in the 1st line treatment of non-squamous NSCLC in the US

Abstract

Aims: To describe cost-effectiveness of pembrolizumab plus platinum and pemetrexed chemotherapy in metastatic, non-squamous, NSCLC patients in the US.

Materials and methods: A model is developed utilizing partitioned survival analysis to estimate the cost-effectiveness of KEYNOTE-189 trial comparators pembrolizumab?+?chemotherapy (carboplatin/cisplatin?+?pemetrexed) vs chemotherapy alone. Clinical efficacy, treatment utilization, health utility, and safety data are derived from the trial and projected over 20 years. For extrapolating survival beyond the trial, a novel SEER population-data approach is applied (primary analysis), with separate estimation via traditional parametric extrapolation methods. Costs for drugs and non-drug disease management are also incorporated. Based on an indirect treatment comparison, cost-effectiveness of pembrolizumab?+?chemotherapy vs pembrolizumab monotherapy is evaluated for patients with programmed death-ligand 1 (PD-L1)?≥?50%.

Results: In the full non-squamous population, pembrolizumab?+?chemotherapy is projected to increase life expectancy by 2.04 years vs chemotherapy (3.96 vs 1.92), for an approximate doubling of life years. Resultant incremental cost-effectiveness ratios (ICERs) are $104,823/QALY and $87,242/life year. In patients with PD-L1?≥?50% and 1–49%, life expectancy is more than doubled (4.53 vs 1.88 years) and (4.87 vs 2.01 years), with a 32% (2.60 vs 1.97 years) increase in PD-L1?<?1% patients. Corresponding incremental costs/quality-adjusted life year (QALY) are $103,402, $66,837, and $183,529 for PD-L1?≥?50%, 1–49%, and <1% groups, respectively. Versus pembrolizumab monotherapy in PD-L1?≥?50% patients, representing current standard of care, pembrolizumab?+?chemotherapy increases life expectancy by 65% (4.53 vs 2.74 years) at an ICER of $147,365/QALY.

Limitations and conclusions: The addition of pembrolizumab to chemotherapy is projected to extend life expectancy to a point not previously seen in previously untreated metastatic non-squamous NSCLC. Although ICERs vary by sub-group and comparator, results suggest pembrolizumab?+?chemotherapy yields ICERs near, or in most cases, well below a 3-times US per capita GDP threshold of $180,000/QALY, and may be a cost-effective first-line treatment for metastatic non-squamous NSCLC patients.     

Cost-effectiveness of cinacalcet in secondary hyperparathyroidism in the United States

Abstract

Objective:

Cinacalcet has been used in controlling secondary hyperparathyroidism (SHPT) in dialysis patients since 2004, but its full economic evaluation has not been conducted from the US perspective. This study assesses the cost-effectiveness of cinacalcet and low-dose vitamin D for the treatment of SHPT in dialysis patients compared with flexible vitamin D.

Methods:

A lifetime patient-level simulation model was developed using ADVANCE trial data, including biomarker levels: parathyroid hormone, calcium, and phosphorus. The impact of the biomarkers on mortality, cardiovascular events, fractures, and parathyroidectomy were estimated from literature: Block, an observational study; Cunningham, a combined analysis of four randomized trials of cinacalcet; and Danese, a study investigating the effect of duration in recommended targets. Baseline event rates were derived from the large dialysis organizations registries. One-way and probabilistic sensitivity analyses (PSA) were conducted.

Results:

The cost-effectiveness ratio for cinacalcet compared with standard of care (vitamin D and phosphate binders) was $54,560 and $72,456/quality-adjusted-life-year (QALY) gained or an incremental cost of $3155 and $2638 per year alive for the Block and Danese variants, respectively. In the Cunningham variant, cost-effectiveness ratio for cinacalcet was $5064/QALY gained or a cost saving of $1068 per year. The difference in the results of the Cunningham variant vs other variants can be explained by the favorable impact of cinacalcet on outcomes, specifically cardiovascular events observed in the Cunningham study. The PSA showed 98% likelihood for cinacalcet to be cost-effective at $100,000/QALY threshold.

Limitations:

Observational data assessing effects on clinical outcomes, trial restriction to use calcium-containing phosphate binders, no utility data in SHPT dialysis population, and insufficient evidence on long-term impact of cinacalcet and vitamin D on biochemical markers.

Conclusions:

Cinacalcet treatment is cost-effective for treatment of SHPT in the US. Due to cost offsets, cinacalcet can reduce annual costs in some scenarios.     

Cost-effectiveness of brentuximab vedotin plus chemotherapy as frontline treatment of stage III or IV classical Hodgkin lymphoma

Objective: The ECHELON-1 trial demonstrated efficacy and safety of brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (A?+?AVD) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) as frontline therapy for stage III/IV classical Hodgkin lymphoma. This analysis evaluated the cost-effectiveness of A?+?AVD from a US healthcare payer perspective.

Methods: The incremental cost-effectiveness ratio (ICER), defined as the incremental costs per quality-adjusted life year (QALY) gained, was estimated using a non-homogenous semi-Markov cohort model with health states defined on progression following frontline treatment, and for those with progression, receipt of autologous stem-cell transplant (ASCT), and progression after ASCT. Patients undergoing ASCT were classified as refractory or relapsed based on timing of progression. Probabilities of progression/death with frontline therapy were based on parametric survival distributions fit to data on modified progression-free survival (mPFS) from ECHELON-1. Duration of frontline treatment and incidence of adverse events were from ECHELON-1. Utility values for patients in the frontline mPFS state were based on EQ-5D data from ECHELON-1. Other inputs were from published sources. A lifetime time horizon was used. Costs and QALYs were discounted at 3%. Analyses were conducted alternately using data on mPFS for the overall and North American populations of ECHELON-1.

Results: The ICER for A?+?AVD vs ABVD was $172,074/QALY gained in the analysis using data on mPFS for the overall population and $69,442/QALY gained in the analysis using data on mPFS for the North American population of ECHELON-1. The ICER is sensitive to estimated costs of ASCT and frontline failure.

Conclusion: The ICER for A?+?AVD vs ABVD based on ECHELON-1 is within the range of threshold values for cost-effectiveness in the US. A?+?AVD is, therefore, likely to be a cost-effective frontline therapy for patients with stage III/IV classical Hodgkin lymphoma from a US healthcare payer perspective.

Trial registration: ClinicalTrials.gov identifier: NCT01712490.     

Cost comparison of prostaglandin analogues: a Canadian population-based analysis

Abstract

Objectives: Glaucoma is a fairly common disease, however, little is known about the costs associated with prostaglandin analogues (PAs). The costs between the three available PAs (Lumigan® (bimatoprost), Xalatan® (latanoprost) and Travatan® (travoprost)) were compared as monotherapy and when adjunctive therapy was used.

Methods: From the Québec drug claims database, all patients who used these drugs for 1 full year were identified. From the Ministry of Health (MoH) perspective, the average cost for all reimbursed costs (drug costs and pharmacist fees) were calculated. Those costs plus the patient out-of-pocket copayments were used for the payer + user (PU) perspective.

Results: Data from 4,653 patients were analysed (3,606 on monotherapy and 1,047 on combination treatment with adjunctive therapy), 59.7% were females, and the average age was 72.6 ± 10.4 years. MoH perspective costs were $410 ± $167 for bimatoprost, $381 ± $145 for latanoprost and $298 ± $121 for travoprost (all differences p<0.001), for patients on monotherapy. Costs of combination treatment with adjunctive therapy were $786 ± $416, $686 ± $313, and $623 ± $521, respectively (travoprost significantly lower than each of the other two p<0.001, others=not significant). Results from the PU perspective were comparable.

Conclusions: Travoprost had the lowest cost, both as monotherapy and in conjunction with other glaucoma treatments. Further comparative pharmacoeconomic evaluation is warranted.