Cost analysis for different sequential treatment regimens for metastatic renal cell carcinoma in China

Abstract

Purpose: Targeted therapies, including sunitinib, sorafenib, axitinib, and everolimus, have recently become the mainstay for the treatment of metastatic renal cell carcinoma (mRCC). The objective of this study was to estimate the costs of sequential treatment regimens for mRCC and associated adverse events (AEs) from the Chinese payers’ perspective.

Methods: Key inputs included in the calculation were patient population, dosing information, incidence rates and associated costs of Grade 3/4 AEs, treatment costs (including drug discount programs), and patients’ progression-free survival (PFS) as a proxy for length of treatment. To calculate PFS, this study identified pivotal clinical trials and generated a reconstructed individual patient data set from the published Kaplan-Meier survival curves. The median PFS from the pooled estimates were used in the calculation. In the base-case scenario, sunitinib was used as first line and the other three therapies were used as second line. Sensitivity analyses were conducted where (1) sorafenib was used as first line, or (2) a third-line therapy was added to the base-case scenario.

Results: In the base case, the cost per patient per treatment month (PPPM) cost was the lowest for sunitinib?+?axitinib among all sequential regimens (¥14,898) and was the highest for sunitinib?+?sorafenib (¥20,103). If sorafenib is used as first line, everolimus had lower per patient per months (PPPM) cost than axitinib (¥17,046 vs ¥23,337), but also had shorter PFS (13.5 months vs 15 months). Second sensitivity analysis with an additional third-line therapy showed consistent results with the base-case scenario; axitinib as second line was the least costly.

Conclusions: This study demonstrates that, for mRCC sequential treatment, sunitinib followed by axitinib generates the highest cost savings from the Chinese payers’ perspective. Future studies are warranted to examine the cost-effectiveness of various mRCC treatment regimens in Chinese populations.     

Real-world dosing and drug costs with everolimus or axitinib as second targeted therapies for advanced renal cell carcinoma: a retrospective chart review in the US

Objective:

To describe dosing patterns and to compare the drug costs per month spent in progression-free survival (PFS) among patients with advanced renal cell carcinoma (aRCC) treated with everolimus or axitinib following a first tyrosine kinase inhibitor (TKI).

Methods:

A medical record retrospective review was conducted among medical oncologists and hematologists/oncologists in the US. Patient eligibility criteria included: (1) age ≥18 years; (2) discontinuation of first TKI (sunitinib, sorafenib, or pazopanib) for medical reasons; (3) initiation of axitinib or everolimus as a second targeted therapy during February 2012–January 2013. Real-world dosing patterns were summarized. Dose-specific drug costs (as of October 2014) were based on wholesale acquisition costs from RED BOOK Online. PFS was compared between everolimus and axitinib using a multivariable Cox proportion hazards model. Everolimus and axitinib drug costs per month of PFS were compared using multivariable gamma regression models.

Results:

A total of 325 patients received everolimus and 127 patients received axitinib as second targeted therapy. Higher proportions of patients treated with axitinib vs everolimus started on a higher than label-recommended starting dose (14% vs 2%) or experienced dose escalation (11% vs 1%) on second targeted therapy. The PFS did not differ significantly between patients receiving everolimus or axitinib (adjusted hazard ratio (HR)?=?1.16; 95% confidence interval [CI]?=?0.73–1.82). After baseline characteristics adjustment, axitinib was associated with 17% ($1830) higher drug costs per month of PFS compared to everolimus ($12,467 vs $10,637; p?<?0.001).

Limitations:

Retrospective observational study design and only drug acquisition costs considered in drug costs estimates.

Conclusions:

Patients with aRCC receiving axitinib as second targeted therapy were more likely to initiate at a higher than label-recommended dose and were more likely to dose escalate than patients receiving everolimus. With similar observed durations of PFS, drug costs were significantly higher—by 17% per month of PFS—with axitinib than with everolimus.     

Cost of adverse events during treatment with everolimus plus exemestane or single-agent chemotherapy in patients with advanced breast cancer in Western Europe

Objective:

Treatment options for recurrent or progressive hormone receptor-positive (HR+) advanced breast cancer include chemotherapy and everolimus plus exemestane (EVE?+?EXE). This study estimates the costs of managing adverse events (AEs) during EVE?+?EXE therapy and single-agent chemotherapy in Western Europe.

Methods:

An economic model was developed to estimate the per patient cost of managing grade 3/4 AEs for patients who were treated with EVE?+?EXE or chemotherapies. AE rates for patients receiving EVE?+?EXE were collected from the phase III BOLERO-2 trial. AE rates for single-agent chemotherapy, capecitabine, docetaxel, or doxorubicin were collected from published clinical trial data. AEs with at least 2% prevalence for any of the treatments were included in the model. A literature search was conducted to obtain costs of managing each AE, which were then averaged across Western European countries (when available). Per patient costs for managing AEs among patients receiving different therapies were reported in 2012 euros (€).

Results:

The EVE?+?EXE combination had the lowest average per patient cost of managing AEs (€730) compared to all chemotherapies during the first year of treatment (doxorubicin: €1230; capecitabine: €1721; docetaxel: €2390). The most costly adverse event among all patients treated with EVE?+?EXE was anemia (on average €152 per patient). The most costly adverse event among all patients treated with capecitabine, docetaxel, or doxorubicin was lymphocytopenia (€861 per patient), neutropenia (€821 per patient), and leukopenia (€382 per patient), respectively.

Conclusions:

The current model estimates that AE management during the treatment of HR+ advanced breast cancer will cost one-half to one-third less for EVE?+?EXE patients than for chemotherapy patients. The consideration of AE costs could have important implications in the context of healthcare spending for advanced breast cancer treatment.     

Budget impact analysis of everolimus for the treatment of hormone receptor positive,human epidermal growth factor receptor-2 negative (HER2−) advanced breast cancer in Kazakhstan

Abstract

Objective:

The aim of this study was to determine the budget impact of everolimus (in combination with letrozole/anastrozole) as a second-line treatment for ER+ HER2? negative advanced and metastatic breast cancer in post-menopausal women.

Research design and methods:

A cumulative cohort model was developed to estimate the 5-year costs associated with introducing everolimus to the Kazakh healthcare system. Two alternative market share scenarios were compared: with everolimus and without everolimus. PFS and OS data were taken from the trial and extrapolated. The background costs of the pre-progressed and post-progressed health states, drug costs and costs associated with adverse events were included in the model.

Results:

The 5-year results from the budget impact analysis demonstrate that the introduction of everolimus leads to a 12% increase in drug costs, a 2% reduction in pre-progression health state costs, a 1% increase in post-progression health state costs, and a 2% reduction in adverse event costs. The net result is only a modest increase in total costs; a 2.69% increase of T201 million, from T7.5 billion to T7.7 billion over a period of 5 years.

Conclusions:

The analysis estimated that, if everolimus were to be introduced to the Kazakh healthcare market for the treatment of ER+ HER2? advanced breast cancer, there would be minimal impact upon overall healthcare expenditure. An increase in drug acquisitions costs was almost exactly offset by a reduction in other healthcare costs, due to improved management of the disease.     

Economic burden of selected adverse events in patients aged ≥65 years with metastatic renal cell carcinoma

Abstract

Objective:

To estimate the costs of adverse events (AEs) in patients aged ≥65 years with metastatic renal cell carcinoma (mRCC).

Methods:

Retrospective study using the linked Surveillance, Epidemiology and End Results (SEER) Medicare database. Study subjects consisted of persons in SEER-Medicare, aged ≥65 years, with evidence of newly diagnosed mRCC between January 1, 2007 and December 31, 2007. Adverse events of interest consisted of Grade 3 or 4 toxicities that have been reported with frequency ≥5% in randomized controlled trials of sunitinib, sorafenib, bevacizumab, and pazopanib (i.e., targeted therapies for mRCC), and included abdominal pain, back pain, diarrhea, dyspnea, extremity pain, fatigue/asthenia, hand-foot syndrome, hypertension, lymphopenia, nausea/vomiting, neutropenia, proteinuria, and thrombocytopenia. Patients in SEER-Medicare with these events were identified based on ICD-9-CM diagnosis codes on Medicare claims. For each AE of interest, costs were tallied among evented patients over 30 days, beginning with the date of each patient’s first mention of the AE, and were compared with those of non-evented patients over a similar 30-day period beginning with an identical ‘shadow’ index date. Total costs were compared on an unadjusted basis and with adjustment for differences in baseline characteristics using a generalized linear model.

Results:

A total of 881 patients with mRCC met study entry criteria; 60% of these patients had Medicare claims with mention of one or more AEs of interest. Events occurring with frequency >20% included abdominal pain, dyspnea, and fatigue/asthenia; 10–20% of study subjects had encounters for back pain, extremity pain, and nausea/vomiting. Mean (standard deviation) total cost of care over 30 days was substantially higher among patients with AEs ($13,944 [$14,529]) compared with those without mention of these events ($1878 [$5264]). Adjusting for differences in baseline characteristics, the mean (95% confidence interval) difference in costs between evented and non-evented patients was $12,410 ($9217–$16,522). Study limitations include problems in event ascertainment due to inaccuracies in ICD-9-CM coding on Medicare claims data, and restriction of the study population to patients with metastatic involvement at initial diagnosis of RCC.

Conclusions:

Costs of care are substantially higher in patients aged ≥65 years with mRCC who experience AEs commonly associated with sunitinib, sorafenib, bevacizumab, and pazopanib. Efforts to prevent and/or better manage these events potentially can reduce healthcare costs.     

The economic burden of common adverse events associated with metastatic colorectal cancer treatment in the United States

Aims: Adverse events (AEs) associated with treatments for metastatic colorectal cancer (mCRC) may compromise the course of treatment, impact quality-of-life, and increase healthcare resource utilization. This study assessed the direct healthcare costs of common AEs among mCRC patients in the US.

Methods: Adult mCRC patients treated with chemotherapy or targeted therapies were identified from administrative claims databases (2009–2014). Up to the first three mCRC treatment episodes per patient were considered and categorized as with or without the AE system/organ category during the episode. Total healthcare costs (2014 USD) were measured by treatment episode and reported on a monthly basis. Treatment episodes with the AE category were matched by treatment type and line of treatment to those without the AE category. Adjusted total cost differences were estimated by comparing costs during treatment episodes with vs without the AE category using multivariate regression models; p-values were estimated with bootstrap.

Results: A total of 4158 patients with ≥1 mCRC treatment episode were included (mean age?=?59 years; 58% male; 60% with liver and 14% with lung metastases; 2,261 [54%] with a second and 1,115 [27%] with a third episode). On average, two treatment episodes were observed per patient with an average length of 166 days per episode. Adjusted monthly total cost difference by AE category included hematologic ($1,480), respiratory ($1,253), endocrine/metabolic ($1,213), central nervous system (CNS; $1,136), and cardiovascular ($1,036; all p?Limitations: Claims do not include information on the cause of AEs, and potentially less severe AEs may not have been reported by the physician when billing the medical service. This study aimed to assess the association between costs and AEs and not the causation of AEs by treatment.

Conclusions: The most costly AEs among mCRC patients were hematologic, followed by respiratory, endocrine/metabolic, CNS, and cardiovascular.     

Costs and effectiveness of fingolimod versus alemtuzumab in the treatment of highly active relapsing-remitting multiple sclerosis in the UK: re-treatment,discount, and disutility

Objective: Patients with relapsing-remitting multiple sclerosis (RRMS) treated with disease modifying therapies (DMTs) who continue to experience disease activity may be considered for escalation therapies such as fingolimod, or may be considered for alemtuzumab. Previous economic modeling used Markov models; applying one alternative technique, discrete event simulation (DES) modeling, allows re-treatment and long-term adverse events (AEs) to be included in the analysis.

Methods: A DES was adapted to model relapse-triggered re-treatment with alemtuzumab and the effect of including ongoing quality-adjusted life year (QALY) decrements for AEs that extend beyond previous 1-year Markov cycles. As the price to the NHS of fingolimod in the UK is unknown, due to a confidential patient access scheme (PAS), a variety of possible discounts were tested. The interaction of re-treatment assumptions for alemtuzumab with the possible discounts for fingolimod was tested to determine which DMT resulted in lower lifetime costs. The lifetime QALY results were derived from modeled treatment effect and short- and long-term AEs.

Results: Most permutations of fingolimod PAS discount and alemtuzumab re-treatment rate resulted in fingolimod being less costly than alemtuzumab. As the percentage of patients who are re-treated with alemtuzumab due to experiencing a relapse approaches 100% of those who relapse whilst on treatment, the discount required for fingolimod to be less costly drops below 5%. Consideration of treatment effect alone found alemtuzumab generated 0.2 more QALYs/patient; the inclusion of AEs up to a duration of 1 year reduced this advantage to only 0.14 QALYs/patient. Modeling AEs with a lifetime QALY decrement found that both DMTs generated very similar QALYs with the difference only 0.04 QALYs/patient.

Conclusions: When the model captured alemtuzumab re-treatment and long-term AE decrements, it was found that fingolimod is cost-effective compared to alemtuzumab, assuming application of only a modest level of confidential PAS discount.     

Cost effectiveness of tyrosine kinase inhibitor therapy in metastatic gastrointestinal stromal tumors

Abstract

Background:

Tyrosine kinase inhibitors (TKIs) such as imatinib mesylate have revolutionized the treatment of primary unresectable and/or metastatic gastrointestinal stromal tumors (GISTs), providing durable disease control and extended survival. Although most patients eventually progress on therapy, dose escalation has been shown to benefit some patients. Sunitinib, a multitargeted kinase inhibitor is effective against imatinib-resistant or intolerant GIST patients. Although the cost of TKI therapy in GIST is high, no other effective systemic treatment options exist.

Objective:

Review pharmacoeconomic studies to determine the cost effectiveness (CE) of 1st- and 2nd-line TKI therapies in GIST.

Methods:

A literature review using Medline and PubMed databases was conducted to identify published economic analyses of TKI therapy in GIST. Key results from these studies were analyzed.

Results:

Six pharmacoeconomic studies were identified, including three analyses of 1st-line imatinib and three analyses of 2nd-line sunitinib. These studies employed various time horizons and discount rates and modeled CE from a number of different perspectives. Most of the pharmacoeconomic studies reviewed used survival as their efficacy endpoint, projecting outcomes beyond available data to model CE. Analyses of 2nd-line sunitinib using survival additionally faced the challenge of adjusting for the effect of placebo crossover to active treatment in the pivotal phase III study. Most studies used Markov techniques with a range of transition probabilities.

Conclusions:

Published pharmacoeconomic studies of 1st- and 2nd-line TKI therapy for advanced GIST employ various time horizons, discount rates, and different CE models. Consequently, these differences make comparisons between studies difficult. Studies of 1st-line imatinib concluded that imatinib was cost effective in advanced, metastatic GIST. Likewise, based on data reviewed here, 2nd-line sunitinib appears to be cost effective in patients with advanced GIST who are intolerant/resistant to imatinib. Key limitations of this review included inconsistency among the studies evaluated with regard to methodologies, countries of origination (currency and healthcare systems), and patient demographics.     

Cost-effectiveness of denosumab vs zoledronic acid for prevention of skeletal-related events in patients with solid tumors and bone metastases in the United States

Abstract

Objective:

With increasing healthcare resource constraints, it has become important to understand the incremental cost-effectiveness of new medicines. Subcutaneous denosumab is superior to intravenous zoledronic acid (ZA) for the prevention of skeletal-related events (SREs) in patients with advanced solid tumors and bone metastases. This study sought to determine the lifetime cost-effectiveness of denosumab vs ZA in this setting, from a US managed-care perspective.

Methods:

A lifetime Markov model was developed, with relative rate reductions in SREs for denosumab vs ZA derived from three pivotal Phase 3 trials involving patients with castration-resistant prostate cancer (CRPC), breast cancer, and non-small-cell lung cancer (NSCLC), and bone metastases. The real-world SRE rates in ZA-treated patients were derived from a large commercial database. SRE and treatment administration quality-adjusted life year (QALY) decrements were estimated with time-trade-off studies. SRE costs were estimated from a nationally representative commercial claims database. Drug, drug administration, and renal monitoring costs were included. Costs and QALYs were discounted at 3% annually. One-way and probabilistic sensitivity analyses were conducted.

Results:

Across tumor types, denosumab was associated with a reduced number of SREs, increased QALYs, and increased lifetime total costs vs ZA. The costs per QALY gained for denosumab vs ZA in CRPC, breast cancer, and NSCLC were $49,405, $78,915, and $67,931, respectively, commonly considered good value in the US. Costs per SRE avoided were $8567, $13,557, and $10,513, respectively. Results were sensitive to drug costs and SRE rates.

Limitations:

Differences in pain severity and analgesic use favoring denosumab over ZA were not captured. Mortality was extrapolated from fitted generalized gamma function beyond the trial duration.

Conclusion:

Denosumab is a cost-effective treatment option for the prevention of SREs in patients with advanced solid tumors and bone metastases compared to ZA. The overall value of denosumab is based on superior efficacy, favorable safety, and more efficient administration.     

Budget impact of everolimus for the treatment of progressive,well-differentiated,non-functional neuroendocrine tumors of gastrointestinal or lung origin that are advanced or metastatic

Background: Advanced neuroendocrine tumors (NETs) are a rare malignancy with considerable need for effective therapies. Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2016 for treatment of adults with progressive, well-differentiated, non-functional NETs of gastrointestinal (GI) or lung origin that are unresectable, locally advanced, or metastatic.

Objective: To assess the 3-year budget impact for a typical US health plan following availability of everolimus for treatment of GI and lung NETs.

Methods An economic model was developed that considered two perspectives: an entire health plan and a pharmacy budget. The total budget impact included costs of drug therapies, administration, hospitalizations, physician visits, monitoring, and adverse events (AEs). The pharmacy model only considered drug costs.

Results: In a US health plan with 1 million members, the model estimated 66 patients with well-differentiated, non-functional, and advanced or metastatic GI NETs and 20 with lung NETs undergoing treatment each year. Total budget impact in the first through third year after FDA approval ranged from $0.0568–$0.1443 per member per month (PMPM) for GI NETs and from $0.0181–$0.0355 PMPM for lung NETs. The total budget impact was lower than the pharmacy budget impact because it included cost offsets from administration and AE management for everolimus compared with alternative therapies (e.g. chemotherapies).

Limitations: Because GI and lung NETs are rare diseases with limited published data, several assumptions were made that may influence interpretation of results.

Conclusions: The budget impact for everolimus was minimal in this rare disease area with a high unmet need, largely due to low disease prevalence. These results should be considered in the context of significant clinical benefits potentially provided by everolimus, including significantly longer progression-free survival (PFS) for advanced GI and lung NET patients.     

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 analysis of secukinumab for the treatment of active psoriatic arthritis: a Canadian perspective

Objective: The study evaluates the cost-effectiveness of secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, vs currently licensed biologic treatments in patients with active psoriatic arthritis (PsA) from a Canadian healthcare system perspective.

Methods: A decision analytic semi-Markov model evaluated the cost-effectiveness of secukinumab 150?mg and 300?mg compared to subcutaneous biologics adalimumab, certolizumab pegol, etanercept, golimumab, and ustekinumab, and intravenous biologics infliximab and infliximab biosimilar in biologic-naive and biologic-experienced patients over a lifetime horizon. The response to treatments was evaluated after 12 weeks by PsA Response Criteria (PsARC) response rates. Non-responders or patients discontinuing initial-line of biologic treatment were allowed to switch to subsequent-line biologics. Model input parameters (Psoriasis Area Severity Index [PASI], Health Assessment Questionnaire [HAQ], withdrawal rates, costs, and resource use) were collected from clinical trials, published literature, and other Canadian sources. Benefits were expressed as quality-adjusted life years (QALYs). An annual discount rate of 5% was applied to costs and benefits. The robustness of the study findings were evaluated via sensitivity analyses.

Results: Biologic-naive patients treated with secukinumab achieved the highest number of QALYs (8.54) at the lowest cost (CAD 925,387) over a lifetime horizon vs all comparators. Secukinumab dominated all treatments, except for infliximab and its biosimilar, which achieved minimally more QALYs (8.58). However, infliximab and its biosimilar incurred more costs than secukinumab (infliximab: CAD 1,015,437; infliximab biosimilar: CAD 941,004), resulting in higher cost-effectiveness estimates relative to secukinumab. In the biologic-experienced population, secukinumab dominated all treatments as it generated more QALYs (8.89) at lower costs (CAD 954,692). Deterministic sensitivity analyses indicated the results were most sensitive to variation in PsARC response rates, change in HAQ, and utility values in both populations.

Conclusions: Secukinumab is either dominant or cost-effective vs all licensed biologics for the treatment of active PsA in biologic-naive and biologic-experienced populations in Canada.     

Tumor treating fields and maintenance temozolomide for newly-diagnosed glioblastoma: a cost-effectiveness study

Abstract

Purpose: The EF-14 trial demonstrated that adding tumor treating fields (TTFields) to maintenance temozolomide (TMZ) significantly extends progression-free survival (PFS) and overall survival (OS) for newly-diagnosed glioblastoma (GBM) patients. This study assessed the cost-effectiveness of TTFields and TMZ for newly-diagnosed GBM from the US healthcare system perspective.

Methods and materials: Outcomes for newly-diagnosed GBM patients were estimated over a lifetime horizon using an area under the curve model with three states: stable disease, progressive disease, or death. The survival model integrated the 5-year EF-14 trial results with long-term GBM epidemiology data and US background mortality rates. Adverse event rates were derived from the EF-14 trial data. Utility values to determine quality-adjusted life-years, adverse event costs, and supportive care costs were obtained from published literature. A 3% discount rate was applied to future costs and outcomes. One-way and probabilistic sensitivity analyses were performed to assess result uncertainty due to parameter variability.

Results: Treatment with TTFields and TMZ was estimated to result in a mean increase in survival of 1.25 life years (95% credible range [CR]?=?0.89–1.67) and 0.96 quality-adjusted life years (QALYs) (95% CR = 0.67–1.30) compared to treatment with TMZ alone. The incremental total cost was $188,637 (95% CR = $145,324–$225,330). The incremental cost-effectiveness ratio (ICER) was $150,452 per life year gained and $197,336 per QALY gained. The model was most sensitive to changes in the cost of TTFields treatment.

Conclusions: Adding TTFields to maintenance TMZ resulted in a substantial increase in the estimated mean lifetime survival and quality-adjusted survival for newly-diagnosed GBM patients. Treatment with TTFields can be considered cost-effective within the reported range of willingness-to-pay thresholds in the US.     

Estimated annual and lifetime labor productivity in the United States, 2016: implications for economic evaluations

Abstract

Background: Human-capital based lifetime productivity estimates are frequently used in cost-of-illness (COI) analyses and, less commonly, in cost-effectiveness analyses (CEAs). Previous US estimates assumed that labor productivity and real earnings both grow by 1% per year.

Objectives: This study presents estimates of annual and lifetime productivity for 2016 using data from the American Community Survey, the American Time Use Survey, and the Current Population Survey, and with varying assumptions about real earnings growth.

Methods: The sum of market productivity (gross annual personal labor earnings adjusted for employer-paid benefits) and the imputed value of non-market time spent in household, caring, and volunteer services was estimated. The present value of lifetime productivity at various ages was calculated for synthetic cohorts using annual productivity estimates, life tables, discount rates, and assumptions about future earnings growth rates.

Results: Mean annual productivity was $57,324 for US adults in 2016, including $36,935 in market and $20,389 in non-market productivity. Lifetime productivity at birth, using a 3% discount rate, is roughly $1.5 million if earnings grow by 1% per year and $1.2 million if future earnings growth averages 0.5% per year.

Conclusions: Inclusion of avoidable productivity losses in societal-perspective CEAs of health interventions is recommended in new US cost-effectiveness guidelines. However, estimates vary depending on whether analysts choose to estimate total productivity or just market productivity, and on assumptions made about growth in future productivity and earnings.     

Cost-effectiveness of continuous subcutaneous apomorphine in the treatment of Parkinson’s disease in the UK and Germany

Abstract

Background:

Parkinson’s disease (PD) is the second most common neurodegenerative disease, affecting ～5.2 million people worldwide. Continuous subcutaneous apomorphine (CSAI) represents an alternative treatment option for advanced PD with motor fluctuation. The purpose of this analysis was to estimate the cost-effectiveness of CSAI compared with Levodopa/carbidopa intestinal gel (LCIG), Deep-Brain-Stimulation (DBS) and Standard-of-care (SOC).

Methods:

A multi-country Markov-Model to simulate the long-term consequences, disease progression (Hoehn & Yahr stages 3–5, percentage of waking-time in the OFF-state), complications, and adverse events was developed. Monte-Carlo simulation accounted for uncertainty. Probabilities were derived from RCT and open-label studies. Costs were estimated from the UK and German healthcare provider’s perspective. QALYs, life-years (LYs), and costs were projected over a life-time horizon.

Results:

UK lifetime costs associated with CSAI amounts to £78,251.49 and generates 2.85 QALYs and 6.28 LYs (€104,500.08, 2.92 QALYs and 6.49 LYs for Germany). Costs associated with LCIG are £130,011.34, achieves 3.06 QALYs and 6.93 LYs (€175,004.43, 3.18 QALYs and 7.18 LYs for Germany). The incremental-cost per QALY gained (ICER) was £244,684.69 (€272,914.58). Costs for DBS are £87,730.22, associated with 2.75 QALYs and 6.38 LYs (€105,737.08, 2.85 QALYs and 6.61 LYs for Germany). CSAI dominates DBS. SOC associated UK costs are £76,793.49; 2.62 QALYs and 5.76 LYs were reached (€90,011.91, 2.73 QALYs and 6 LYs for Germany).

Conclusions:

From a health economic perspective, CSAI is a cost-effective therapy and could be seen as an alternative treatment to LCIG or DBS for patients with advanced PD.     

Cost-effectiveness analysis of secukinumab in ankylosing spondylitis from the Canadian perspective

Aim: To assess the cost-effectiveness of interleukin (IL)-17A inhibitor secukinumab vs the currently licensed biologic therapies in ankylosing spondylitis (AS) patients from a Canadian healthcare system perspective.

Methods: A decision analytic model (semi-Markov) evaluated the cost-effectiveness of secukinumab 150?mg compared to certolizumab pegol, adalimumab, golimumab, etanercept and etanercept biosimilar, and infliximab and infliximab biosimilar in a biologic-naïve population, over 60 years of time horizon (lifetime). The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50) response rate was used to assess treatment response at week 12. Non-responders or patients discontinuing initial-line of biologic therapy were allowed to switch to subsequent-line biologics. Model input parameters (short-term and long-term changes in BASDAI and Bath Ankylosing Spondylitis Functional Index [BASFI], withdrawal rates, adverse events, costs, resource use, utilities, and disutilities) were obtained from clinical trials, published literature, and other Canadian sources. Benefits were expressed as quality-adjusted life years (QALYs). Cost and benefits were discounted with an annual discount rate of 1.5% for all treatments.

Results: In the biologic-naïve population, secukinumab 150?mg dominated all comparators, as patients treated with secukinumab 150?mg achieved the highest QALYs (16.46) at the lowest cost (CAD 533,010) over a lifetime horizon vs comparators. In the deterministic sensitivity analysis, results were most sensitive to changes in baseline BASFI non-responders, BASDAI 50 at 3 months and discount rates. Probabilistic sensitivity analysis showed that secukinumab 150?mg demonstrated higher probability of achieving maximum net monetary benefit vs all comparators at various cost thresholds.

Conclusions: This analysis demonstrates that secukinumab 150?mg is the most cost-effective treatment option for biologic-naïve AS patients compared to certolizumab pegol, adalimumab, golimumab, etanercept and etanercept biosimilar, and infliximab and infliximab biosimilar for a lifetime horizon in Canada. Treatment with secukinumab translates into substantial benefits for patients and the healthcare system.     

Healthcare and economic burden of adverse events among patients with chronic myelogenous leukemia treated with BCR-ABL1 tyrosine kinase inhibitors

Objectives: BCR-ABL1 tyrosine kinase inhibitors (TKIs) are established treatments for chronic myelogenous leukemia (CML); however, they are associated with infrequent, but clinically serious adverse events (AEs). The objective of this analysis was to assess healthcare resource utilization and costs associated with AEs, previously identified using the FDA Adverse Event Reporting System (FAERS) in another study, among TKI-treated patients.

Methods: Adult patients with ≥1 inpatient or ≥2 outpatient ICD-9-CM diagnosis codes for CML and ≥1 claim for a TKI treatment between January 1, 2006 and September 30, 2012 were identified from the Commercial and Medicare MarketScan databases. The first claim for a TKI was designated as the index event. Patients were required to have no TKI treatment during a 12-month baseline period. Healthcare resource utilization and costs associated with select AEs having the strongest association with TKI treatment (femoral arterial stenosis [FAS], peripheral arterial occlusive disease [PAOD], intermittent claudication, coronary artery stenosis [CAS], pericardial effusion, pleural effusion, malignant pleural effusion, conjunctival hemorrhage) were evaluated during a 12-month follow-up period.

Results: The study sample included 2,005 CML patients receiving TKI therapy (mean age?=?56 years; 56% male). Among all evaluated AEs, the highest mean inpatient healthcare costs were observed for FAS ($16,800 per patient) and PAOD ($14,263 per patient), which had total mean medical costs (inpatient?+?outpatient) of $17,015 and $15,154 per patient, respectively. Mean outpatient healthcare costs were highest for CAS ($1,861 per patient), followed by intermittent claudication ($947 per patient), PAOD ($891 per patient), and pleural effusion ($890 per patient). Total mean medical costs for fluid retention-related AEs, including pericardial effusion and pleural effusion, were $2,797 and $1,908 per patient, respectively.

Conclusions: The healthcare costs of AEs identified in the FAERS as having the strongest association with TKI treatment are substantial. Vascular stenosis-related AEs, including FAS and PAOD, have the highest cost burden.     

Adverse event-related costs for systemic metastatic breast cancer treatment among female Medicaid beneficiaries

Objective: This retrospective study compared the real-world incidence and costs of systemic treatment-related adverse events (AEs) in patients with metastatic breast cancer in a Medicaid population.

Methods: Insurance claims data for adult women who received biologic or chemotherapy (± hormonal therapy) for metastatic breast cancer between 2006–2013 were extracted from the Truven Health MarketScan^® Multi-State Medicaid database. Incidence of AEs (per 100 person years) and average monthly AE-related healthcare costs (per-patient-per-month) during each line of therapy (first or later lines) were estimated. The association between AEs and total all-cause healthcare costs was estimated using multivariable regression.

Results: A total of 729 metastatic breast cancer patients were analyzed. Hematological (202.3 per 100 person years) and constitutional AEs (289.6 per 100 person years) were the most common class of AEs reported. Unadjusted per-patient-per-month AE-related expenditure by class were highest for hematological AEs ($1524), followed by gastrointestinal ($839) and constitutional AEs ($795), with anemia ($942), nausea/vomiting ($699), and leukopenia/neutropenia ($550) having incurred the highest total AE-related costs. Adjusted total all-cause monthly costs increased with the number of AEs ($19,701 for >7 AEs, $16,264 for 4???6 AEs, and $13,731 for 1???3 AEs) compared to no AEs ($5908) (all p?Conclusions: Among metastatic breast cancer patients treated with systemic therapy in a Medicaid population, AEs were associated with significant increases in costs, which increased with the number of AEs experienced. Therapies associated with a lower incidence of AEs may reduce cost burden and improve patient outcomes.     

The budget impact of brodalumab for the treatment of moderate-to-severe plaque psoriasis on US commercial health plans

Introduction: Brodalumab is a new biologic approved by the US Food and Drug Administration in 2017 for the treatment of moderate-severe psoriasis. This study evaluated the impact of the introduction of brodalumab on the pharmacy budget on US commercial health plans.

Methods: An Excel-based health economic decision analytic model with a US health plan perspective was developed. The model incorporated published moderate-to-severe psoriasis prevalence data; market shares of common biologic drugs, including adalimumab, ustekinumab, secukinumab, ixekizumab, and etanercept, used for the treatment of moderate–severe psoriasis; 2017-year Wholesale Acquisition Costs for the biologic drugs; drug dispensing fee; patient co-pay; and drug contracting discount. Total annual health plan costs for the biologic drugs were estimated. Scenarios with different proportions of patients treated with brodalumab were compared to a control scenario when no brodalumab was used.

Results: In a hypothetical commercial health plan covering two million members, 7,038 moderate-to-severe psoriasis patients were estimated to be eligible for treatment with brodalumab. Prior to brodalumab approval, the proportions of patients treated by other biologics were estimated at 50.8% for adalimumab, 13.5% for ustekinumab, 14.1% for secukinumab, 4.4% for ixekizumab, and 17.2% for etanercept. With a 20% drug price discount applied to all biologics, the annual health plan costs for brodalumab, adalimumab, ustekinumab, secukinumab, ixekizumab, and etanercept were estimated at $37,224, $49,166, $55,084, $56,061, $64,396, and $57,170, respectively. When no brodalumab is used, the total annual pharmacy budget for the biologics used among these patients was estimated at $414,362,647. Among scenarios where the proportions of brodalumab usage were 3%, 8%, 16%, and 30%, the total annual pharmacy cost was estimated to be reduced by $3,698,129, $9,861,677, $19,723,355, and $36,981,290, respectively.

Conclusion: Based on the economic model, brodalumab has the potential to substantially reduce pharmacy expenditures for the treatment of patients with moderate-to-severe plaque psoriasis in the US.