Cost-effectiveness analysis of febuxostat in patients with gout in Spain

Objectives Cost-effectiveness of febuxostat compared with allopurinol in the treatment of hyperuricemia in patients with gout.

Methods Costs, clinical outcomes, and QALYs were estimated using a Markov model. Febuxostat 80?mg and 120?mg sequentially, used as first line and second line therapy, was compared with allopurinol 300?mg. Patients switched to the next treatment in the sequence according to a dichotomous response vs no response (target serum urate level < 6?mg/dl outcome) after 3 months of active treatment. A 3% discount rate and 5-year time horizon were applied. Perspective: National Health System.

Results The addition of febuxostat to any therapeutic strategy was an efficient option, with incremental cost-effectiveness ratios (ICER) compared with allopurinol 300?mg ranging from €5268–€9737.

Conclusions Febuxostat is a cost-effective treatment in Spain for the management of hyperuricemia in gout patients, with ICERs far below accepted Spanish efficiency thresholds (30 000€/QALY).     

Cost-effectiveness of sequential urate lowering therapies for the management of gout in Singapore

Abstract

Aims: Allopurinol is the most common urate lowering therapy (ULT) used to treat gout but may cause life-threatening severe cutaneous adverse reactions (SCAR) in a small number of patients. Risk of SCAR is increased for patients with the HLA-B*58:01 genotype. When alternative ULT is required, febuxostat or probenecid are recommended. The aim of this study was to conduct a cost-utility analysis of sequential ULT treatment strategies for gout, including strategies with and without HLA-B*58:01 genotyping prior to treatment initiation, with a view to inform optimal gout management in Singapore.

Materials and methods: A Markov model was developed from the Singapore healthcare payer perspective. Reflecting local practice, 12 different treatment strategies containing at least one ULT (allopurinol, febuxostat, probenecid) were evaluated in adults with gout. Response rates (SUA < 6mg/dL) were derived from an in-house network meta-analysis and from published literature. Incremental cost-effectiveness ratios (ICERs) were calculated over a 30-year time horizon, with costs and benefits discounted at 3% per annum. Sensitivity analyses were conducted to explore uncertainties.

Results: Sequential treatment of allopurinol 300?mg/day-allopurinol 600?mg/day-probenecid (“standard of care”) was cost-effective compared to no ULT, with an ICER of SGD1,584/QALY. Allopurinol300-allopurinol600-probenecid-febuxostat sequence compared to allopurinol300-allopurinol600-probenecid had an ICER of SGD11,400/QALY. All other treatment strategies were dominated by preceding strategies. Treatment strategies incorporating HLA-B*58:01 genotyping before ULT use were dominated by the corresponding non-genotyping strategy.

Conclusions: Current standard of care (allopurinol300-allopurinol 600-probenecid) for gout is cost-effective compared with no ULT in the local context. Febuxostat is unlikely to be cost-effective in Singapore at current prices unless it is used last-line.     

The cost-effectiveness of extended-release calcifediol versus paricalcitol for the treatment of secondary hyperparathyroidism in stage 3–4 CKD

Abstract

Aims: Patients with chronic kidney disease (CKD) not on dialysis frequently have vitamin D insufficiency (VDI) and secondary hyperparathyroidism (SHPT), which are associated with an increased risk of cardiovascular (CV) disease, fracture, CKD progression, and death. This study estimated the cost-effectiveness of extended-release calcifediol (ERC) vs paricalcitol for the treatment of patients with CKD stages 3–4 that have SHPT and VDI.

Materials and methods: An economic analysis of SHPT treatments among a hypothetical cohort of 1,000 patients with CKD Stage 3 and 4 with SHPT and VDI was developed to estimate differences in the rates and costs of CV events, fractures, CKD stage progression, and mortality in patients treated with ERC and paricalcitol. A Markov model was developed with 1-year cycles and a 5-year time horizon from a US Medicare payer perspective with costs valued in 2017?US dollars.

Results: The outcomes of the model were rates of clinical events, total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Across a 1,000-person cohort, ERC was the dominant (less costly, more effective) treatment strategy when compared with paricalcitol. Treatment with ERC resulted in cost savings of $14.8?M (95% CI = –$10.0?M–$45.2?M) and an incremental gain of 340 QALYs (95% CI = 200–496) compared to treatment with paricalcitol.

Limitations: Bridging biochemical levels to clinical outcomes may not represent real-world risk of the clinical events modeled. Future real-world outcomes of patients treated with ERC and paricalcitol may be used to evaluate the model results.

Conclusions: This model demonstrated favorable short- and long-term clinical benefits associated with the use of ERC in patients with CKD Stage 3 and 4 with SHPT and VDI, suggesting ERC may be cost-effective from the Medicare perspective compared to paricalcitol.     

Cost-effectiveness of natalizumab versus fingolimod for the treatment of relapsing multiple sclerosis

Abstract

Background:

With the addition of new agents for the treatment of multiple sclerosis (MS) (e.g., fingolimod), there is a need to evaluate the relative value of newer therapies in terms of cost and effectiveness, given healthcare resource constraints in the United States.

Objective:

To assess the cost-effectiveness of natalizumab vs fingolimod in patients with relapsing MS.

Methods:

A decision analytic model was developed to estimate the incremental cost per relapse avoided of natalizumab and fingolimod from a US managed care payer perspective. Two-year costs of treating patients with MS included drug acquisition costs, administration and monitoring costs, and costs of treating MS relapses. Effectiveness was measured in terms of MS relapses avoided (data from AFFIRM and FREEDOMS trials). One-way and probabilistic sensitivity analyses were conducted to assess uncertainty.

Results:

Mean 2-year estimated treatment costs were $86,461 (natalizumab) and $98,748 (fingolimod). Patients receiving natalizumab had a mean of 0.74 relapses avoided per 2 years vs 0.59 for fingolimod. Natalizumab dominated fingolimod in the incremental cost-effectiveness analysis, as it was less costly and more effective in reducing relapses. One-way sensitivity analysis showed the results of the model were robust to changes in drug acquisition costs, administration costs, and costs of treating MS relapses. Probabilistic sensitivity analysis showed natalizumab was cost-effective 95.1% of the time, at a willingness-to-pay (WTP) threshold of $0 per relapse avoided, increasing to 96.3% of the time at a WTP threshold of $50,000 per relapse avoided.

Limitations:

Absence of data from direct head-to-head studies comparing natalizumab and fingolimod, use of relapse rate reduction rather than sustained disability progression as primary model outcome, assumption of 100% adherence to MS treatment, and not capturing adverse event costs in the model.

Conclusions:

Natalizumab dominates fingolimod in terms of incremental cost per relapse avoided, as it is less costly and more effective.     

Economic burden of comorbid chronic kidney disease and diabetes

Objective: To estimate real-world healthcare utilization and expenditures across the spectrum of chronic kidney disease (CKD), as determined by estimated glomerular filtration rate (eGFR) categories in patients with diabetes.

Methods: This study employed a retrospective cohort study design using the Truven Healthcare and Claims Dataset from 2009–2012. Index date was defined as the first eGFR value during a continuous enrollment period of 24 months. Cohorts of patients were stratified by Kidney Disease: Improving Global Outcomes CKD stage based on eGFR (stages 1: ≥90?mL/min/1.73?m²; 2: 60–89; 3A: 45–59; 3B: 30–44; 4: 15–29; 5: <15). Healthcare expenditures (total patient and payer paid claims) and utilization (number of claims or visits) were estimated 12-months post-index date using generalized linear modeling and negative binomial modeling, respectively, after adjusting for baseline characteristics.

Results: Of 130,098 patients with an index eGFR value and 24-months continuous enrolment, 64,521 (49.59%) were in stage 1 CKD, 47,816 (36.75%) were in stage 2, 13,377 (10.28%) were in stage 3A, 3,217 (2.47%) were in stage 3B, 898 (0.69%) were in stage 4, and 269 (0.21%) were in stage 5. Patients in stages 3A, 3B, and 4 CKD had 1.32 (95% CI?=?1.22–1.43), 1.59 (95% CI?=?1.41–1.80), and 2.65 (95% CI?=?2.23–3.14) times higher rates of diabetes-associated inpatient visits, respectively, compared with stage 1 CKD patients. Patients in stages 3A, 3B, and 4 CKD had increased incremental total annual healthcare expenditures of $1,732 (95% CI?=?$1,109–$2,356), $2,632 (95% CI?=?$1,647–$3,619), and $6,949 (95% CI?=?$5,466–$8,432), respectively, compared with stage 1 CKD patients.

Limitations: The claims data were generated for billing and reimbursement, not for research purposes.

Conclusions: These real-world data suggest an incremental and significant increase in economic burden in diabetes as kidney function declines, starting with moderate (stage 3A) CKD.     

Work productivity loss due to flares in patients with chronic gout refractory to conventional therapy

Abstract

Objective:

Joint pain and swelling during gout flares may lead to considerable morbidity and disability, having an impact on patient work productivity and social participation. The objective of this study was to assess how gout flares affect these activities in patients with chronic gout refractory to conventional therapy.

Methods:

A 1-year prospective observational study was conducted among patients with symptomatic disease in the United States in 2001. Inclusion criteria required patients (1) to be age 18 years or older, (2) to have documented, crystal-proven gout, (3) to have symptomatic gout, and (4) to be intolerant or unresponsive to conventional therapy, reflected by SUA?≥?6.0?mg/dL. Patients were evaluated every 2 months. At each visit, patients completed a gout diary, which included number of flares experienced, duration and severity of each flare, and whether the flare caused: (1) work loss, (2) missed appointments or social events, or (3) impairment of self-care activities. The Short-Form Health Survey (SF-36) was also completed each visit.

Results:

Analyses were restricted to those who completed the first 6 months of the study (n?=?81). Mean number of flares per patient per year was 8.8. Of the patients who were <65 years, 78% reported at least 1 work day lost due to a gout attack during the year. Mean annual work day loss for those <65 years was 25.1 days. A total of 545 of patients reported at least one flare per year that impaired social activities, with a mean of 17.1 social days lost and 52% reported at least one flare per year that compromised normal self-care activities, with a mean of 16.9 days impairment. Correlations between the diary reports and activity-related questions from the SF-36 were significantly positive.

Limitations:

The study is limited by small sample size, lack of reference group, and inability to explicitly collect employment information. Age under 65 years was used as a proxy for employment eligibility.

Conclusion:

Flares in patients with chronic gout refractory to conventional therapy significantly affect patient work productivity and social activities.     

Cost-effectiveness of golimumab for the treatment of patients with moderate-to-severe ulcerative colitis in Quebec using a patient level state transition microsimulation

Objective: To conduct cost-effectiveness analyses comparing the addition of golimumab to the standard of care (SoC) for treatment of patients with moderate-to-severe ulcerative colitis (UC) who are refractory to conventional therapies in Quebec (Canada).

Methods: An individual patient state transition microsimulation model was developed to project health outcomes and costs over 10 years, using a payer perspective. The incremental benefit estimates for golimumab were driven by induction response and risk of a flare. Flare risks post-induction were derived for golimumab from the PURSUIT maintenance trial and extension study, while those for SoC were derived from the placebo arms of the Active Ulcerative Colitis Trials (ACT) 1 and 2. Other inputs were derived from multiple sources, including retrospective claims analyses and literature. Costs are reported in 2014 Canadian dollars. A 5% annual discount rate was applied to costs and quality-adjusted life-years (QALYs).

Results: Compared with SoC, golimumab was projected to increase the time spent in mild disease or remission states, decrease flare rates, and increase QALYs. These gains were achieved with higher direct medical costs. The incremental cost-effectiveness ratio for golimumab vs SoC was $63,487 per QALY.

Limitations: The long-term flare projections for SoC were based on the data available from the ACT 1 and 2 placebo arms, as data were not available from the PURSUIT maintenance or extension trial. Additionally, the study was limited to only SoC and golimumab, due to the availability of individual patient data to analyze.

Conclusion: This economic analysis concluded that treatment with golimumab is likely more cost-effective vs SoC when considering cost-effectiveness acceptability thresholds from $50,000–$100,000 per QALY.     

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 dipeptidyl peptidase-4 inhibitor monotherapy versus sulfonylurea monotherapy for people with type 2 diabetes and chronic kidney disease in Thailand

Objective: With a high prevalence of chronic kidney disease (CKD) in type 2 diabetes (T2DM) in Thailand, the appropriate treatment for the patients has become a major concern. This study aimed to evaluate long-term cost-effective of dipeptidyl peptidase-4 (DPP-4) inhibitor monothearpy vs sulfonylurea (SFU) monotherapy in people with T2DM and CKD.

Methods: A validated IMS CORE Diabetes Model was used to estimate the long-term costs and outcomes. The efficacy parameters were identified and synthesized using a systematic review and meta-analysis. Baseline characteristics and cost parameters were obtained from published studies and hospital databases in Thailand. Costs were expressed in 2014?US Dollars. Outcomes were presented as an incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to estimate parameter uncertainty.

Results: From a societal perspective, treatment with DPP-4 inhibitors yielded more quality-adjusted life years (QALYs) (0.024) at a higher cost (>66,000 Thai baht (THB) or >1,829.27 USD) per person than SFU, resulting in the ICER of >2.7 million THB/QALY (>74,833.70 USD/QALY). The cost-effectiveness results were mainly driven by differences in HbA1c reduction, hypoglycemic events, and drug acquisition cost of DPP-4 inhibitors. At the ceiling ratio of 160,000 THB/QALY (4,434.59 USD/QALY), the probability that DPP-4 inhibitors are cost-effective compared to SFU was less than 10%.

Conclusions: Compared to SFU, DPP-4 inhibitor monotherapy is not a cost-effective treatment for people with T2DM and CKD in Thailand.     

A cost-effectiveness analysis of using azacitidine vs. decitabine in treating patients with myelodysplastic syndromes

Abstract

Objective:

Azacitidine and decitabine are used to treat patients with myelodysplastic syndromes (MDS) in the United States (US). This study sought to assess their relative cost-effectiveness.

Design and methods:

The authors developed a cost-effectiveness Markov model (1-month cycles) tracking hypothetical cohorts of MDS patients treated with azacitidine or decitabine over 2 years. The model used a US payer perspective and 2009 costs. Health states modeled included MDS with Transfusion Dependence, MDS with Transfusion Independence, Progression to Acute Myelogenous Leukemia (AML), and Death. Incremental cost-effectiveness outcomes included cost per quality-adjusted life year (QALY), cost per life year (LY), cost per patient-month of transfusion independence, and cost per case of AML progression avoided. One-way sensitivity analyses were performed on key model parameters.

Results:

Compared to decitabine, azacitidine was associated with better survival (1.512 LYs vs 1.292), more QALYs gained (1.041 vs 0.870), more patient-months with transfusion independence (8.328 vs 6.224), and a greater proportion of patients avoiding progression to AML (50.9% vs 28.5%). Total per-patient costs over 2 years for azacitidine were lower than for decitabine ($150,322 vs $166, 212).

Limitations:

To inform and update the model over time, it will be important that randomized or observational clinical studies be conducted to directly compare azacitidine and decitabine, provide new information on how these medicines are used, and on their relative clinical effectiveness.

Conclusion:

Results demonstrate that azacitidine provides greater clinical benefit and costs less than decitabine across all key outcomes. These results accentuate the positive role of azacitidine in providing cost-effective care for MDS.     

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 daclatasvir plus sofosbuvir-based regimen for treatment of hepatitis C virus genotype 3 infection in Canada

Objective:

New regimens for the treatment of chronic hepatitis C virus (HCV) genotype 3 have demonstrated substantial improvement in sustained virologic response (SVR) compared with existing therapies, but are considerably more expensive. The objective of this study was to evaluate the cost-effectiveness of two novel all-oral, interferon-free regimens for the treatment of patients with HCV genotype 3: daclatasvir plus sofosbuvir (DCV?+?SOF) and sofosbuvir plus ribavirin (SOF?+?RBV), from a Canadian health-system perspective.

Methods:

A decision analytic Markov model was developed to compare the effect of various treatment strategies on the natural history of the disease and their associated costs in treatment-naïve and treatment-experienced patients. Patients were initially distributed across fibrosis stages F0–F4, and may incur disease progression through fibrosis stages and on to end-stage liver disease complications and death; or may achieve SVR. Clinical efficacy, health-related quality-of-life, costs, and transition probabilities were based on published literature. Probabilistic sensitivity analysis was performed to assess parameter uncertainty associated with the analysis.

Results:

In treatment-naive patients, the expected quality-adjusted life years (QALYs) for interferon-free regimens were higher for DCV?+?SOF (12.37) and SOF?+?RBV (12.48) compared to that of pINF?+?RBV (11.71) over a lifetime horizon, applying their clinical trial treatment durations. The expected costs were higher for DCV?+?SOF ($170,371) and SOF?+?RBV ($194,776) vs pINF?+?RBV regimen ($90,905). Compared to pINF?+?RBV, the incremental cost-effectiveness ratios (ICER) were $120,671 and $135,398 per QALYs for DCV?+?SOF and SOF?+?RBV, respectively. In treatment-experienced patients, DCV?+?SOF regimen dominated the SOF?+?RBV regimen. Probabilistic sensitivity analysis indicated a 100% probability that a DCV?+?SOF regimen was cost saving in treatment-experienced patients.

Conclusion:

Daclatasvir plus sofosbuvir is a safe and effective option for the treatment of chronic HCV genotype 3 patients. This regimen could be considered a cost-effective option following a first-line treatment of peg-interferon/ribavirin treatment experienced patients with HCV genotype-3 infection.     

Cost-effectiveness of angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers as first-line treatment in autosomal dominant polycystic kidney disease

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a rare kidney disorder impacting ～1:2,500 individuals among the general US population. Hypertension is a significant predictor of ADPKD progression, and a risk factor for development of cardiovascular disease (CVD), the most common cause for mortality among ADPKD patients. Angiotensin-converting enzymes inhibitors (ACE-I) are widely used as first-line treatment in ADPKD for the management of hypertension. However, their cost-effectiveness relative to other hypertensive medications, such as angiotensin II receptor blockers (ARB), has never been assessed.

Objective: To determine if ARB are more cost-effective than ACE-Is as first-line treatment in ADPKD.

Methods: A Markov-state decision model was constructed for estimation of cost and outcome benefits in hypertensive ADPKD patients. Transition probabilities were extrapolated from a retrospective cohort study comparing chronic kidney disease (CKD) stage transitions in ADPKD patients. Annual pharmaceutical costs per average daily dose per CKD stage were extracted from a US healthcare claims database. Median total healthcare costs per CKD stage or transplant were extracted from the published literature. The time horizon was set to 30 years, with 1-year duration to cycle shift. A cost-effectiveness analysis was conducted to estimate the incremental cost-effectiveness ratio (ICER) of ACE-I vs ARB per additional year of prevented transplant and/or death. A one-way probabilistic sensitivity analysis was conducted, with 10% variation in probabilities and cost.

Results: Total annual healthcare costs accrued after 30 years among ADPKD patients taking ACE-Is was estimated to be $3,505,028.41, compared to ARB at $3,644,327.65. Life expectancy was increased by 1.39 years among patients taking ACE-I. Approximate 10-year survival in patients taking ACE-Is was 47% compared to ARB at 34%.

Conclusions: ACE-I dominated ARB and displayed greater cost-effectiveness due to lower cost and increased capacity to prolong years of life without transplant or death among hypertensive ADPKD patients. This model strengthens the value of ACE-I over ARB as first-line treatment for hypertension management in ADPKD patients.     

The cost-effectiveness of disease-modifying therapies for the treatment of relapsing-remitting multiple sclerosis

Background: The safety and efficacy of disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) has been established; however, it is not clear which provides optimal value, given benefit-risk profiles and costs.

Aims: To compare the cost-effectiveness of current DMTs for patients with RRMS in the US.

Materials and methods: A Markov model predicting RRMS course following initiation of a DMT was created comparing outcomes (e.g. relapses, disease progression) and costs of natalizumab (NTZ), dimethyl fumarate (DMF), and peginterferon beta-1a (PEG) with fingolimod (FIN), glatiramer acetate (GA, 20?mg daily), and subcutaneous interferon beta-1a (IFN, 44?mcg), respectively, over 10 years. RRMS and secondary-progressive MS (SPMS) EDSS state transitions were predicted in 3-month cycles in which patients were at risk of death, relapse, or discontinuation. Upon DMT discontinuation, natural history progression and relapse rates were applied. Incremental cost-effectiveness ratios (ICERs) were estimated for the cost per relapse avoided, relapse-free years gained, progression avoided, and progression-free years gained. The impact of model parameters on outcomes was evaluated via one-way sensitivity analyses.

Results: Costs ranged from $561,177 (NTZ) to $616,251 (GA). NTZ, DMF, and PEG were dominant (less costly and more effective) compared to FIN, GA, and IFN, respectively, for all ICERs. Variability in drug costs and parameters that affected drug cost accrual (e.g. discontinuation rates and the decision to drop out after SPMS conversion) had a considerable impact on ICERs.

Limitations: Several simplifying assumptions were made that may represent potential limitations of this analysis (e.g. a constant treatment effect over time was assumed).

Conclusions: The results from this analysis suggest that the NTZ, DMF, and PEG are cost-effective DMT choices compared to FIN, GA, and IFN, respectively. The actual impact on a particular plan will vary based on drug pricing and other factors affecting drug cost accrual.     

Cost-effectiveness of natalizumab vs fingolimod for the treatment of relapsing-remitting multiple sclerosis: analyses in Sweden

Abstract

Objective:

To assess the cost-effectiveness of natalizumab vs fingolimod over 2 years in relapsing-remitting multiple sclerosis (RRMS) patients and patients with rapidly evolving severe disease in Sweden.

Methods:

A decision analytic model was developed to estimate the incremental cost per relapse avoided of natalizumab and fingolimod from the perspective of the Swedish healthcare system. Modeled 2-year costs in Swedish kronor of treating RRMS patients included drug acquisition costs, administration and monitoring costs, and costs of treating MS relapses. Effectiveness was measured in terms of MS relapses avoided using data from the AFFIRM and FREEDOMS trials for all patients with RRMS and from post-hoc sub-group analyses for patients with rapidly evolving severe disease. Probabilistic sensitivity analyses were conducted to assess uncertainty.

Results:

The analysis showed that, in all patients with MS, treatment with fingolimod costs less (440,463 Kr vs 444,324 Kr), but treatment with natalizumab results in more relapses avoided (0.74 vs 0.59), resulting in an incremental cost-effectiveness ratio (ICER) of 25,448 Kr per relapse avoided. In patients with rapidly evolving severe disease, natalizumab dominated fingolimod. Results of the sensitivity analysis demonstrate the robustness of the model results. At a willingness-to-pay (WTP) threshold of 500,000 Kr per relapse avoided, natalizumab is cost-effective in >80% of simulations in both patient populations.

Limitations:

Limitations include absence of data from direct head-to-head studies comparing natalizumab and fingolimod, use of relapse rate reduction rather than sustained disability progression as the primary model outcome, assumption of 100% adherence to MS treatment, and exclusion of adverse event costs in the model.

Conclusions:

Natalizumab remains a cost-effective treatment option for patients with MS in Sweden. In the RRMS patient population, the incremental cost per relapse avoided is well below a 500,000 Kr WTP threshold per relapse avoided. In the rapidly evolving severe disease patient population, natalizumab dominates fingolimod.     

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 analysis of utidelone plus capecitabine for metastatic breast cancer in China

Abstract

Objective: To estimate the cost-effectiveness of utidelone plus capecitabine therapy compared to capecitabine alone in patients with metastatic breast cancer (MBC) resistant to anthracyclines and taxanes treatment in the Chinese context and provide a reference for the marketing of utidelone in China.

Methods: A Markov model was developed based on the NCT02253459 clinical trial to simulate the clinical course of patients with metastatic breast cancer who had received taxanes and anthracycline therapy. The quality-adjusted life years (QALYs) and Incremental Cost Effectiveness Ratio (ICER) were then analyzed to evaluate the benefits. Two-parametric Weibull distribution was conducted to fit PFS and OS curves by using R. Sensitivity analyses were performed to evaluate the stability of the model designed.

Results: The addition of utidelone increased the cost and QALYs by $13,370.25 and 0.1961, respectively, resulting in an increased ICER of $68,180.78 per QALY. The most sensitive influential parameter on ICER was the price of utidelone. At the threshold of willingness-to-pay (WTP) of $24,380 (3 per capita GDP of China), the cost of utidelone per 30?mg of less than $18.5, $33.7, and greater than $48.8 resulted in a 100%, 50%, and 0% possibility of cost-effectiveness, respectively. The addition of utidelone was not cost-effective when it was $115.4 per 30?mg—the price of its analog paclitaxel. In consideration of varied economics levels across China, cost-effectiveness could be achieved with the price of utidelone ranging from $5.2 to $35.9.

Limitations: The survival curves extended beyond the follow-up time horizon, of which data were generated not from the real analyses but from our established two-parameter Weibull survival model.

Conclusion: It is recommended that the price of utidelone would be less than $18.5 per 30?mg in order to obtain cost-effectiveness for metastatic breast cancer patients resistant to anthracyclines and taxanes treatment in China.     

Cost-effectiveness analysis of intra-articular injections of a high molecular weight bioengineered hyaluronic acid for the treatment of osteoarthritis knee pain

Objective:

To determine the cost-effectiveness of bioengineered hyaluronic acid (BioHA, 1% sodium hyaluronate) intra-articular injections in treating osteoarthritis knee pain in poor responders to conventional care (CC) including non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics.

Methods:

Two decision analytic models compared BioHA treatment with either continuation of patient’s baseline CC with no assumption of disease progression (Model 1), or CC including escalating care costs due to disease progression (NSAIDs and analgesics, corticosteroid injections, and surgery; Model 2). Analyses were based on patients who received two courses of 3-weekly intra-articular BioHA (26-week FLEXX Trial?+?26-week Extension Study). BioHA group costs included fees for physician assessment and injection regimen, plus half of CC costs. Cost-effectiveness ratios were expressed as averages and incremental costs per QALY. One-way sensitivity analyses used the 95% confidence interval (CI) of QALYs gained in BioHA-treated patients, and ±20% of BioHA treatment and CC costs. Probabilistic sensitivity analyses were performed for Model 2.

Results:

For 214 BioHA patients, the average utility gain was 0.163 QALYs (95% CI?=??0.162 to 0.488) over 52 weeks. Model 1 treatment costs were $3469 and $4562 for the BioHA and CC groups, respectively; sensitivity analyses showed BioHA to be the dominant treatment strategy, except when at the lower end of the 95% CI. Model 2 annual treatment costs per QALY gained were $1446 and $516 for the BioHA and CC groups, respectively. Using CC as baseline strategy, the incremental cost-effectiveness ratio (ICER) of BioHA was $38,741/QALY gained, and was sensitive to response rates in either the BioHA or CC groups.

Conclusion:

BioHA is less costly and more effective than CC with NSAIDs and analgesics, and is the dominant treatment strategy. Compared with escalating CC, the $38,741/QALY ICER of BioHA remains within the $50,000 per QALY willingness-to-pay threshold to adopt a new technology.     

Economic modelling of costs associated with outcomes reported for type 2 diabetes mellitus (T2DM) patients in the CANVAS and EMPA-REG cardiovascular outcomes trials

Aims: To model direct medical costs associated with reductions in cardiovascular disease (CVD) events in T2DM patients reported in the CANVAS and EMPA-REG trials, which assessed the cardiovascular safety of canagliflozin and empagliflozin, respectively.

Materials and methods: Costs were modeled from a US managed care organization (MCO) perspective for the CVD outcomes included in both trials: three-point major adverse cardiovascular event (MACE) and its components (cardiovascular-related death, nonfatal myocardial infarction, nonfatal stroke), as well as heart failure requiring hospitalization. The rate of CVD events averted (difference between study drug and placebo) was projected to the portion of an MCO T2DM population matching the respective trial’s inclusion criteria. A targeted literature search for paid amounts directly associated with each CVD event provided the unit costs, which were applied to the projected number of events averted, to calculate costs avoided per member per year (PMPY). One-way sensitivity analyses were performed on events averted, unit costs, and percentages of trial-applicable patients.

Results: Based on three-point MACE events averted, costs avoided PMPY of $6.17 (range: $1.27–$10.94) for CANVAS and $2.75 ($0.19–$4.83) for EMPA-REG were estimated. Costs avoided for individual components of MACE ranged from $0.77 to $3.84 PMPY for CANVAS and from -$0.97 (additional costs) to $1.54 for EMPA-REG. PMPY costs avoided for heart failure were $2.72 for CANVAS and $1.32 for EMPA-REG.

Limitations and conclusions: Models assumed independent, non-recurrent outcomes and were restricted to medical costs directly associated with the trial-reported events. The reductions in CVD events in T2DM patients reported for both CANVAS and EMPA-REG project to a positive cost avoidance for these events in an MCO population. The analysis did not include an assessment of the impact on total cost, as the costs associated with adverse events, drug utilization or other clinical outcomes were not examined.