The real-world cost-effectiveness of adjuvant trastuzumab in HER-2/neu-positive early breast cancer in Taiwan

Background: Trastuzumab was considered a cost-effective adjuvant treatment for HER 2-positive early breast cancer. Since 2010, the Taiwanese National Health Insurance (NHI) has started to reimburse for 1-year adjuvant treatment. This study aims to provide an updated cost-effectiveness analysis from the NHI perspective, which explores assumptions about long-term cardiac toxicity and treatment benefit of 1-year adjuvant treatment sequentially after chemotherapy.

Methods: A Markov model was used to evaluate the cost-effectiveness of 1-year adjuvant trastuzumab for HER-2/neu positive early breast cancer over a 20-year life-time horizon. A probability sensitivity analysis using Monte Carlo simulation was performed to characterize uncertainties in the expected outcomes, which are expressed as an incremental costs effectiveness ratio (ICER, cost/QALY). A willingness-to-pay threshold of 3-times the per capita gross domestic product was adopted according to the WHO definition. The Taiwan per capita gross domestic product in 2015 was US$22,355; thus, a threshold was considered as NT$2,011,950 (US$67 065, 1USD?=30 NTD in 2015).

Results: The model showed that adjuvant trastuzumab treatment in HER-2/neu positive early breast cancer yielded 1.631 quality-adjusted life-years (QALY) compared with no trastuzumab treatment. The ICER was US $51,863 per QALY gained in the base-case scenario. The Monte Carlo simulation by varying all variables simultaneously demonstrated that the probability of cost-effectiveness at the willingness-to-pay threshold of US$67,065 was 50% for 1-year adjuvant trastuzumab.

Conclusions: From this real-world study, 1-year adjuvant trastuzumab treatment is likely to be a cost-effective therapy for patients with HER-2 positive breast cancer at the willingness-to-pay threshold of 3-times GDP per capita in Taiwan.     

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.     

Cost-effectiveness of lenalidomide plus dexamethasone vs bortezomib plus melphalan and prednisone in transplant-ineligible US patients with newly-diagnosed multiple myeloma

Objective:

To conduct a cost-effectiveness assessment of lenalidomide plus dexamethasone (Rd) vs bortezomib plus melphalan and prednisone (VMP) as initial treatment for transplant-ineligible patients with newly-diagnosed multiple myeloma (MM), from a US payer perspective.

Methods:

A partitioned survival model was developed to estimate expected life-years (LYs), quality-adjusted LYs (QALYs), direct costs and incremental costs per QALY and LY gained associated with use of Rd vs VMP over a patient’s lifetime. Information on the efficacy and safety of Rd and VMP was based on data from multinational phase III clinical trials and a network meta-analysis. Pre-progression direct costs included the costs of Rd and VMP, treatment of adverse events (including prophylaxis) and routine care and monitoring associated with MM. Post-progression direct costs included costs of subsequent treatment(s) and routine care and monitoring for progressive disease, all obtained from published literature and estimated from a US payer perspective. Utilities were obtained from the aforementioned trials. Costs and outcomes were discounted at 3% annually.

Results:

Relative to VMP, use of Rd was expected to result in an additional 2.22 LYs and 1.47 QALYs (discounted). Patients initiated with Rd were expected to incur an additional $78,977 in mean lifetime direct costs (discounted) vs those initiated with VMP. The incremental costs per QALY and per LY gained with Rd vs VMP were $53,826 and $35,552, respectively. In sensitivity analyses, results were found to be most sensitive to differences in survival associated with Rd vs VMP, the cost of lenalidomide and the discount rate applied to effectiveness outcomes.

Conclusions:

Rd was expected to result in greater LYs and QALYs compared with VMP, with similar overall costs per LY for each regimen. Results of this analysis indicated that Rd may be a cost-effective alternative to VMP as initial treatment for transplant-ineligible patients with MM, with an incremental cost-effectiveness ratio well within the levels for recent advancements in oncology.     

Cost-effective analysis of clopidogrel versus aspirin for high risk patients with established peripheral arterial disease in China

Abstract

Objective: To assess the cost-effectiveness of clopidogrel versus aspirin for high risk patients (pre-existing symptomatic atherosclerosis or multi-vascular territory involvement) with established peripheral arterial disease (PAD) for secondary prevention of atherothrombotic events in a Chinese setting.

Methods: A Markov model with a lifetime horizon was developed from the perspective of the national healthcare system in China. The primary outputs are quality adjusted life years (QALYs), direct medical costs, and the incremental cost-effectiveness ratios (ICERs). Clinical efficacy data were obtained from the CAPRIE trial. Drug acquisition cost, other direct medical costs, and utilities were from pricing records and the literature. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were conducted to test the robustness of the model on all parameters.

Results: In patients with pre-existing atherosclerosis, 2 years of treatment with clopidogrel and aspirin would yield total QALYs of 8.776 and 8.576 at associated costs of ¥18,777 ($2,838) and ¥12,302 ($1,859), respectively, resulting in an ICER of ¥32,382 ($4,893) per QALY gained. In patients with PVD, secondary prevention with the same drugs would expect to lead to total QALYs of 8.836 and 8.632 at associated costs of ¥18,518 ($2,798) and ¥12,041 ($1,820), respectively, resulting in a corresponding ICER of ¥31,743 ($4,797) per QALY gained. The results were most sensitive to the discount rate for future outcomes and costs. The PSA indicated that the probability of clopidogrel being cost-effective was 100% at the willingness-to-pay threshold of 3-times GDP.

Conclusions: Secondary prevention with clopidogrel is an attractive cost-effective option compared with aspirin for high risk patients with established PAD from the perspective of the national healthcare system in Chinese settings.     

Cost-effectiveness analysis of neoadjuvant pertuzumab and trastuzumab therapy for locally advanced,inflammatory, or early HER2-positive breast cancer in Canada

Abstract

Objective:

The NeoSphere trial demonstrated that the addition of pertuzumab to trastuzumab and docetaxel for the neoadjuvant treatment of HER2-positive locally advanced, inflammatory, or early breast cancer (eBC) resulted in a significant improvement in pathological complete response (pCR). Furthermore, the TRYPHAENA trial supported the benefit of neoadjuvant dual anti-HER2 therapy. Survival data from these trials is not yet available; however, other studies have demonstrated a correlation between pCR and improved event-free survival (EFS) and overall survival (OS) in this patient population. This study represents the first Canadian cost-effectiveness analysis of pertuzumab in the neoadjuvant treatment of HER2-positive eBC.

Methods:

A cost-utility analysis (CUA) was conducted using a three health state Markov model (‘event-free’, ‘relapsed’, and ‘dead’). Two separate analyses were conducted; the first considering total pCR (ypT0/is ypN0) data from NeoSphere, and the second from TRYPHAENA. Published EFS and OS data partitioned for patients achieving/not achieving pCR were used in combination with the percentage achieving pCR in the pertuzumab trials to estimate survival. This CUA included published utility values and direct medical costs including drugs, treatment administration, management of adverse events, supportive care, and subsequent therapy. To address uncertainty, a probabilistic sensitivity analysis (PSA) and alternative scenarios were explored.

Results:

Both analyses suggested that the addition of pertuzumab resulted in increased life-years and quality-adjusted life-years (QALYs). The incremental cost per QALY ranged from $25,388 (CAD; NeoSphere analysis) to $46,196 (TRYPHAENA analysis). Sensitivity analyses further support the use of pertuzumab, with cost-effectiveness ratios ranging from $9230–$64,421. At a threshold of $100,000, the addition of pertuzumab was cost-effective in nearly all scenarios (93% NeoSphere; 79% TRYPHAENA).

Conclusion:

Given the improvement in clinical efficacy and a favorable cost per QALY, the addition of pertuzumab in the neoadjuvant setting represents an attractive treatment option for HER2-positive eBC patients.     

Cost-effectiveness of pembrolizumab for the adjuvant treatment of resected high-risk stage III melanoma in the United States

Abstract

Aims: To evaluate the cost-effectiveness of adjuvant pembrolizumab relative to observation alone following complete resection of high-risk stage III melanoma with lymph node involvement, from a US health system perspective.

Materials and methods: A Markov cohort model with four health states (recurrence-free, locoregional recurrence, distant metastases, and death) was developed to estimate costs, life-years, and quality-adjusted life-years (QALYs) associated with pembrolizumab vs observation over a lifetime (46-year) horizon. Using a parametric multi-state modeling approach, transition probabilities starting from recurrence-free were estimated based on patient-level data from KEYNOTE-054 (NCT02362594), a direct head-to-head phase 3 trial. Post-recurrence transition probabilities were informed by real-world retrospective data and clinical trials in advanced melanoma. Health state utilities and adverse event-related disutility were derived from KEYNOTE-054 trial data and published literature. Costs of drug acquisition and administration, adverse events, disease management, and terminal care were estimated in 2018?US dollars. Deterministic and probabilistic sensitivity analyses were conducted to assess robustness.

Results: Over a lifetime horizon, adjuvant pembrolizumab and observation were associated with total QALYs of 9.24 and 5.95, total life-years of 10.54 and 7.15, and total costs of $489,820 and $440,431, respectively. The resulting incremental cost-effectiveness ratios (ICERs) for pembrolizumab vs observation were $15,009/QALY and $14,550/life-year. Across the range of input values and assumptions tested in deterministic sensitivity analyses, pembrolizumab ranged from being a dominant strategy to having an ICER of $57,449/QALY vs observation. The ICER was below a willingness-to-pay threshold of $100,000/QALY in 90.2% of probabilistic simulations.

Limitations: Long-term extrapolation of outcomes was based on interim results from KEYNOTE-054, with a median follow-up of 15?months.

Conclusions: Based on common willingness-to-pay benchmarks, pembrolizumab is highly cost-effective compared with observation alone for the adjuvant treatment of completely resected stage III melanoma in the US.     

Cost effectiveness of atazanavir-ritonavir versus lopinavir-ritonavir in treatment-naïve human immunodeficiency virus-infected patients in the United States

Abstract

Objective:

To evaluate lifetime cost effectiveness of atazanavir-ritonavir (ATV?+?r) versus lopinavir-ritonavir (LPV/r), both with tenofovir-emtricitabine, in US HIV-infected patients initiating first-line antiretroviral therapy.

Methods:

A Markov microsimulation model was developed to calculate quality-adjusted life-years (QALYs) based on CD4 and HIV RNA levels, coronary heart disease (CHD), AIDS, opportunistic infections (OIs), diarrhea, and hyperbilirubinemia. A million-member cohort of HIV-1-infected, treatment-naïve adults progressed at 3-month intervals through eight health states. Baseline characteristics, virologic suppression, cholesterol changes, and diarrhea and hyperbilirubinemia rates were based on 96-week CASTLE trial results. HIV mortality, OI rates, adherence, costs, utilities, and CHD risk were from literature and experts.

Limitations:

The incremental cost-effectiveness ratio (ICER) may be overestimated because the ATV?+?r treatment effect was based on an intention-to-treat analysis. The QALY weights used for diarrhea, hyperbilirubinemia, and CHD events are uncertain; however, the ICER remained <$50,000/QALY when these values were varied in sensitivity analyses.

Results:

ATV?+?r patients received first-line therapy longer than LPV/r patients (97.3 vs. 70.7 months), had longer quality-adjusted survival (11.02 vs. 10.76 years), similar overall survival (18.52 vs. 18.51 years), and higher costs ($275,986 vs. 269,160). ATR?+?r patients had lower rates of AIDS (19.08 vs. 20.05 cases/1,000 patient-years), OIs (0.44 vs. 0.52), diarrhea (1.27 vs. 6.26), and CHD events (5.44 vs. 5.51), but higher hyperbilirubinemia rates (6.99 vs. 0.25). ATV?+?r added 0.26 QALYs at a cost of $6826, for $26,421/QALY.

Conclusions:

By more effectively reducing viral load with less gastrointestinal toxicity and a better lipid profile, ATV?+?r lowered rates of AIDS and CHD, increased quality-adjusted survival, and was cost effective (<$50,000/QALY) compared with LPV/r.     

Cost-effectiveness analysis of tissue plasminogen activator in acute ischemic stroke in Iran

Aims: Tissue plasminogen activator (tPA) is used to treat acute ischemic stroke up to 4.5?h after symptom onset. Its cost-effectiveness in developing countries is not specified yet. This study aimed to study cost-effectiveness of tPA in Iran.

Methods: This is a cost-effectiveness analysis from the perspective of the third party payer to compare IV tPA with no tPA of ischemic stroke. A Markov model with a lifetime horizon was used to analyze the costs and outcomes. Cost data were extracted from the 94 patients admitted in two hospitals in Iran. All costs were calculated based on US dollars in 2016. Quality-adjusted life years (QALY) were extracted from previously published literature. Cost-effectiveness was determined by calculating ICER by TreeAge Pro 2011 software.

Results: Lifetime costs of no tPA strategy were higher than tPA ($10,718 in the no tPA group compared with $8,796 in the tPA group). The tPA arm gained 0.20 QALY compared with no tPA. ICER was $8,471 per QALY. ICER value suggests that tPA is cost-effective compared with no tPA.

Limitations: The limitations of the present study are the reliance on calculated QALY value of other countries and difficulty in accessing patients treated with tPA.

Conclusions: The balance of hospitalization and rehabilitation costs and QALYs support the conclusion that treatment with intravenous tPA in the 4.5-h time window is cost-effective from the perspectives of the third party payer and inclusion of tPA in the insurance benefit package being reasonable.     

Cost-effectiveness analysis of ramucirumab treatment for patients with hepatocellular carcinoma who progressed on sorafenib with α-fetoprotein concentrations of at least 400 ng/ml

Abstract

Objective: This study aimed to compare the cost-effectiveness of ramucirumab versus placebo for patients with hepatocellular carcinoma who progressed on sorafenib with α-fetoprotein concentrations (AFP) of at least 400?ng/ml in the United States.

Methods: A Markov model was constructed to assess the cost-effectiveness of ramucirumab. Health outcomes were measured as quality-adjusted life years (QALYs). With TreeAge software, the disease process was modeled as three health states: progression-free survival (PFS), progressive disease (PD), and death. Costs were extracted from the REACH-2 trial, and utility was derived from published literature. Incremental cost-effectiveness ratios (ICERs) were calculated to compare ramucirumab with placebo. Probabilistic sensitivity analyses were developed to examine the robustness of the results.

Results: In the base case analysis, ramucirumab therapy had a cost of $55,508.41 and generated 0.54 QALYs, while placebo therapy had a cost of $761.09 and generated 0.47 QALYs, leading to an additional $54,747.32 in costs and 0.07 QALYs. The ICER was $782,104.57 per QALY, which was much higher than the willingness-to-pay threshold of $100,000 per QALY. According to sensitivity analyses, the utility of PD in the two groups was the dominant parameter influencing the ICER.

Conclusion: Although ramucirumab was associated with prolonged survival for patients with advanced hepatocellular carcinoma who progressed on sorafenib treatment with an AFP of at least 400?ng/ml, it is not a cost-effective treatment from a United States payer perspective.     

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 evaluation of nivolumab for the treatment of second-line advanced squamous NSCLC in Canada: a comparison of modeling approaches to estimate and extrapolate survival outcomes

Background Lung cancer is the most common type of cancer in the world and is associated with significant mortality. Nivolumab demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients with advanced squamous non-small cell lung cancer (NSCLC) who were previously treated. The cost-effectiveness of nivolumab has not been assessed in Canada. A contentious component of projecting long-term cost and outcomes in cancer relates to the modeling approach adopted, with the two most common approaches being partitioned survival (PS) and Markov models. The objectives of this analysis were to estimate the cost-utility of nivolumab and to compare the results using these alternative modeling approaches.

Methods Both PS and Markov models were developed using docetaxel and erlotinib as comparators. A three-health state model was used consisting of progression-free, progressed disease, and death. Disease progression and time to progression were estimated by identifying best-fitting survival curves from the clinical trial data for PFS and OS. Expected costs and health outcomes were calculated by combining health-state occupancy with medical resource use and quality-of-life assigned to each of the three health states. The health outcomes included in the model were survival and quality-adjusted-life-years (QALYs).

Results Nivolumab was found to have the highest expected per-patient cost, but also improved per-patient life years (LYs) and QALYs. Nivolumab cost an additional $151,560 and $140,601 per QALY gained compared to docetaxel and erlotinib, respectively, using a PS model approach. The cost-utility estimates using a Markov model were very similar ($152,229 and $141,838, respectively, per QALY gained).

Conclusions Nivolumab was found to involve a trade-off between improved patient survival and QALYs, and increased cost. It was found that the use of a PS or Markov model produced very similar estimates of expected cost, outcomes, and incremental cost-utility.     

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 of fingolimod versus interferon beta-1a for relapsing remitting multiple sclerosis in the United States

Abstract

Objective:

Fingolimod has been shown to be more efficacious than interferon (IFN) beta-1a, but at a higher drug acquisition cost. The aim of this study was to assess the cost-effectiveness of fingolimod compared to IFN beta-1a in patients diagnosed with relapsing-remitting multiple sclerosis (RRMS) in the US.

Methods:

A Markov model comparing fingolimod to intramuscular IFN beta-1a using a US societal perspective and a 10-year time horizon was developed. A cohort of 37-year-old patients with RRMS and a Kurtzke Expanded Disability Status Scale score of 0–2.5 were assumed. Data sources included the Trial Assessing Injectable Interferon vs FTY720 Oral in Relapsing–Remitting Multiple Sclerosis (TRANSFORMS) and other published studies of MS. Outcomes included costs in 2011 US dollars, quality-adjusted life years (QALYs), number of relapses avoided, and incremental cost-effectiveness ratios (ICERs).

Results:

Compared to IFN beta-1a, fingolimod was associated with fewer relapses (0.41 vs 0.73 per patient per year) and more QALYs gained (6.7663 vs 5.9503), but at a higher cost ($565,598 vs $505,234). This resulted in an ICER of $73,975 per QALY. Results were most sensitive to changes in drug costs and the disutility of receiving IFN beta-1a. Monte Carlo simulation demonstrated fingolimod was cost-effective in 35% and 70% of 10,000 iterations, assuming willingness-to-pay thresholds of $50,000 and $100,000 per QALY, respectively.

Limitations:

Event rates were primarily derived from a single randomized clinical trial with 1-year duration of follow-up and extrapolated to a 10-year time horizon. Comparison was made to only one disease-modifying drug—intramuscular IFN beta-1a.

Conclusion:

Fingolimod use is not likely to be cost-effective compared to IFN beta-1a unless fingolimod cost falls below $3476 per month or a higher than normal willingness-to-pay threshold is accepted by decision-makers.     

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 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.     

Incremental net monetary benefit of ocrelizumab relative to subcutaneous interferon β-1a

Aim: Disease-modifying therapies (DMTs) impact the natural history of relapsing forms of multiple sclerosis (RRMS) by reducing annual relapse rates and slowing disability progression. The effect of DMTs on indirect costs has not been consistently explored in cost-effectiveness studies thus far. The value to patients of an emerging DMT, ocrelizumab, was quantified in comparison to subcutaneous interferon beta-1a (IFNβSC) for the prevalent RRMS population with mild-to-moderate disability in the US, based on two Phase 3 trials, OPERA I and OPERA II, of ocrelizumab vs IFNβSC in RRMS.

Materials and methods: A Markov model was developed to compare disability progression as measured by Expanded Disability Status Scale (EDSS) and relapse outcomes over a 30-year horizon for ocrelizumab vs IFNβSC. Direct, indirect, and informal costs (2016?US dollars) and utilities for EDSS health states were obtained from the literature. Hazard ratios for disability progression and relapse rates were estimated from clinical trials. Value was assessed by calculating the net monetary benefit (NMB), defined as the monetary value of discounted quality-adjusted life years (QALYs) minus total costs, where the value of a QALY was $150,000. One-way sensitivity analyses were conducted.

Results: Ocrelizumab was associated with an incremental gain of 0.84 QALYs and cost savings of $287,713 relative to IFNβSC, resulting in an incremental NMB (INMB) of $413,611 per person over 30 years. The INMB increased by $151,763 for those initiating ocrelizumab at EDSS level 1 vs level 4. Influential parameters were QALY value, treatment costs, and disability progression; however, all sensitivity analyses indicated that the INMB for ocrelizumab relative to IFNβSC was ≥$300,000 per person.

Conclusions: Ocrelizumab provides greater value to RRMS patients compared with IFNβSC. Initiating ocrelizumab at lower EDSS levels leads to a greater cumulative value due to slower disability progression, which extends years with higher quality-of-life.     

Nilotinib versus dasatinib as second-line therapy in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase who are resistant or intolerant to imatinib: a cost-effectiveness analysis based on real-world data

Objective: To evaluate the cost-effectiveness of second-line nilotinib vs dasatinib among patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+?CML-CP) who are resistant or intolerant to imatinib, from a US third-party perspective.

Methods: A lifetime partitioned survival model was developed to compare the costs and effectiveness of nilotinib vs dasatinib, which included four health states: CP on treatment, CP post-discontinuation, progressive disease (accelerated phase [AP] or blast crisis [BC]), and death. Time on treatment, progression-free survival, and overall survival of nilotinib and dasatinib were estimated using real-world comparative effectiveness data. Parametric survival models were used to extrapolate outcomes beyond the study period. Drug treatment costs, medical costs, and adverse event costs were obtained from the literature and publicly available databases. Utilities of health states were derived from the literature. Incremental cost-effectiveness ratios, including incremental cost per life-year (LY) gained and incremental cost per quality-adjusted life-year (QALY) gained, were estimated comparing nilotinib and dasatinib. Deterministic sensitivity analyses were performed by varying patient characteristics, cost, and utility inputs.

Results: Over a lifetime horizon, nilotinib-treated patients were associated with 11.7 LYs, 9.1 QALYs, and a total cost of $1,409,466, while dasatinib-treated patients were associated with 9.5 LYs, 7.3 QALYs, and a total cost of $1,422,122. In comparison with dasatinib, nilotinib was associated with better health outcomes (by 2.2 LYs and 1.9 QALYs) and lower total costs (by $12,655). Deterministic sensitivity analysis results showed consistent findings in most scenarios.

Limitations: In the absence of long-term real-world data, the lifetime projection could not be validated.

Conclusions: Compared with dasatinib, second-line nilotinib was associated with better life expectancy, better quality-of-life, and lower costs among patients with Ph+?CML-CP who were resistant or intolerant to imatinib.     

Cost-effectiveness of axicabtagene ciloleucel for adult patients with relapsed or refractory large B-cell lymphoma in the United States

Abstract

Purpose: Axicabtagene ciloleucel (axi-cel) was recently approved for treatment of relapsed or refractory (R/R) large B-cell lymphoma (LBCL) following two or more prior therapies. As the first CAR T-cell therapy available for adults in the US, there are important questions about clinical and economic value. The objective of this study was to assess the cost-effectiveness of axi-cel compared to salvage chemotherapy using a decision model and a US payer perspective.

Materials and methods: A decision model was developed to estimate life years (LYs), quality-adjusted life years (QALYs), and lifetime cost for adult patients with R/R LBCL treated with axi-cel vs salvage chemotherapy (R-DHAP). Patient-level analyses of the ZUMA-1 and SCHOLAR-1 studies were used to inform the model and to estimate the proportion achieving long-term survival. Drug and procedure costs were derived from US average sales prices and Medicare reimbursement schedules. Future healthcare costs in long-term remission was derived from per capita Medicare spending. Utility values were derived from patient-level data from ZUMA-1 and external literature. One-way and probabilistic sensitivity analyses evaluated uncertainty. Outcomes were calculated over a lifetime horizon and were discounted at 3% per year.

Results: In the base case, LYs, QALYs, and lifetime costs were 9.5, 7.7, and $552,921 for axi-cel vs 2.6, 1.1, and $172,737 for salvage chemotherapy, respectively. The axi-cel cost per QALY gained was $58,146. Cost-effectiveness was most sensitive to the fraction achieving long-term remission, discount rate, and axi-cel price. The likelihood that axi-cel is cost-effective was 95% at a willingness to pay of $100,000 per QALY.

Conclusion: Axi-cel is a potentially cost-effective alternative to salvage chemotherapy for adults with R/R LBCL. Long-term follow-up is necessary to reduce uncertainties about health outcomes.     

Cost-effectiveness of several atypical antipsychotics in orally disintegrating tablets compared with standard oral tablets in the treatment of schizophrenia in the United States

Abstract

Objective:

Although the use of innovative drug delivery systems, like orally disintegrating antipsychotic tablets (ODT), may facilitate medication adherence and help reduce the risk of relapse and hospitalization, no information is available about the comparative cost-effectiveness of standard oral tablets (SOT) vs ODT formulations in the treatment of schizophrenia. This study compared the cost-effectiveness of olanzapine ODT and olanzapine SOT in the usual treatment of outpatients with schizophrenia from a US healthcare perspective. The study also compared olanzapine ODT with risperidone and aripiprazole, two other atypical antipsychotics available in both ODT and SOT formulations.

Methods:

Published medical literature and a clinical expert panel were used to populate a 1-year Monte Carlo Micro-simulation model. The model captures clinical and cost parameters including adherence levels, treatment discontinuation by reason, relapse with and without inpatient hospitalization, quality-adjusted life years (QALYs), treatment-emergent adverse events, healthcare resource utilization, and associated costs. Key outcomes were total annual direct cost per treatment, QALY, and incremental cost-effectiveness (ICER) per 1 QALY gained.

Results:

Based on model projections, olanzapine ODT therapy was more costly ($9808 vs $9533), but more effective in terms of a lower hospitalization rate (15% vs 16%) and better QALYs (0.747 vs 0.733) than olanzapine SOT therapy. Olanzapine ODT was more cost-effective than olanzapine SOT (ICER: $19,643), more cost-effective than risperidone SOT therapy (ICER: $39,966), and dominant (meaning less costly and more effective) than risperidone ODT and aripiprazole in ODT or SOT formulations.

Limitations:

Lack of head-to-head randomized studies comparing the three studied atypical antipsychotics required making input assumptions that need further study.

Conclusions:

This micro-simulation found that the utilization of olanzapine ODT for the treatment of schizophrenia is predicted to be more cost-effective than any other ODT or SOT formulations of the studied atypical antipsychotic medications.