Effectiveness of asfotase alfa for treatment of adults with hypophosphatasia: results from a global registry.

BACKGROUND: Hypophosphatasia (HPP) is a rare inherited disease caused by deficient activity of tissue-nonspecific alkaline phosphatase. Many adults with HPP have a high burden of disease, experiencing chronic pain, fatigue, limited mobility, and dental issues, contributing to decreased health-related quality of life (HRQoL). HPP may be treated with the enzyme replacement therapy asfotase alfa though real-world data in adults are limited. This analysis was conducted to assess the clinical effectiveness of asfotase alfa among adults in the Global HPP Registry. METHODS: The Global HPP Registry is an observational, prospective, multinational study. Adults ≥ 18 years of age were included in this analysis if they had serum alkaline phosphatase (ALP) activity below the age- and sex-adjusted reference ranges, and/or ALPL variant(s), and received asfotase alfa for ≥ 6 months. Mobility was assessed with the 6-Minute Walk Test (6MWT), and patient-reported outcomes tools were used to assess pain (Brief Pain Inventory-Short Form), quality of life (36-item Short Form Health Survey, version 2 [SF-36v2]), and disability (Health Assessment Questionnaire-Disability Index) at multiple time points from baseline through Month 36. Data were collected as per usual standard of care; patients may not have contributed data at all time points. RESULTS: A total of 190 patients met the inclusion criteria. For patients with ≥ 1 follow-up measurement, the mean distance achieved on 6MWT increased from 404 m (range 60-632 m) at baseline (n = 31) to 484 m at Month 12 (range 240-739 m; n = 18) and remained above baseline through Month 36 (n = 7). Improvements in mean self-reported pain severity scores ranged from - 0.72 (95% CI: - 1.23, - 0.21; n = 38) to - 1.13 (95% CI: - 1.76, - 0.51; n = 26) and were observed at all time points. Improvements in the Physical Component Summary score of SF-36v2 were achieved by Month 6 and sustained throughout follow-up. There was a trend toward improvement in the Mental Component Summary score of SF-36v2 at most time points, with considerable fluctuations from Months 12 (n = 28) through 36 (n = 21). The most frequent adverse events were injection site reactions. CONCLUSIONS: Adults with HPP who received asfotase alfa for ≥ 6 months experienced improvements in mobility, physical function, and HRQoL, which were maintained over 3 years of follow-up. REGISTRATION: NCT02306720; EUPAS13514.

Hospitalization risk in patients with schizophrenia treated with dose-equivalent antipsychotics.

This study compared the risk of hospitalization among adults with schizophrenia being treated with equivalent dose ranges of lurasidone versus aripiprazole, olanzapine, quetiapine, or risperidone. Administrative claims data for this analysis came from the IBM MarketScan Commercial, Medicare Supplemental, and Multi-State Medicaid databases between January 2011 and June 2017. The study included adults with schizophrenia who initiated treatment with an antipsychotic and were continuously enrolled for 360 days prior to and following the date of the initial antipsychotic prescription. Risk of all-cause and schizophrenia-related hospitalization among patients who received lurasidone monotherapy versus aripiprazole, olanzapine, quetiapine, or risperidone in equivalent dose ranges were assessed. Marginal structural models that accounted for preindex characteristics, changes in antipsychotic treatment, and time-varying covariates assessed differences between lurasidone and other second-generation antipsychotics on all-cause and schizophrenia-related hospitalizations. A sensitivity analysis was conducted without the dose-equivalence requirement. A total of 20,212 patients met the study inclusion criteria. Compared with those treated with lurasidone monotherapy, the adjusted risk of all-cause hospitalization was significantly higher among patients treated with olanzapine (adjusted rate ratio [aRR], 1.49; P = .04), quetiapine (aRR, 1.64; P = .01), or risperidone (aRR, 1.47; P = .04), but not aripiprazole (aRR, 1.24; P = .28). A similar, non-statistically significant pattern of adjusted risks of schizophrenia-related hospitalizations was observed. A sensitivity analysis without the dose-equivalence requirement produced consistent results. As hospitalization is a major cost driver of direct healthcare cost, lurasidone may be a cost-saving treatment option for patients with schizophrenia.

The Additional Costs per Month of Progression-Free Survival and Overall Survival: An Economic Model Comparing Everolimus with Cabozantinib, Nivolumab, and Axitinib for Second-Line Treatment of Metastatic Renal Cell Carcinoma.

BACKGROUND: When considering optimal second-line treatments for metastatic renal cell carcinoma (mRCC), clinicians and payers seek to understand the relative clinical benefits and costs of treatment. OBJECTIVE: To use an economic model to compare the additional cost per month of overall survival (OS) and of progression-free survival (PFS) for cabozantinib, nivolumab, and axitinib with everolimus for the second-line treatment of mRCC from a third-party U.S. payer perspective. METHODS: The model evaluated mean OS and PFS and costs associated with drug acquisition/administration; adverse event (AE) treatment; monitoring; and postprogression (third-line treatment, monitoring, and end-of-life costs) over 1- and 2-year horizons. Efficacy, safety, and treatment duration inputs were estimated from regimens' pivotal clinical trials; for everolimus, results were weighted across trials. Mean 1- and 2-year OS and mean 1-year PFS were estimated using regimens' reported OS and PFS Kaplan-Meier curves. Dosing and administration inputs were consistent with approved prescribing information and the clinical trials used to estimate efficacy and safety inputs. Cost inputs came from published literature and public data. Additional cost per additional month of OS or PFS was calculated using the ratio of the cost difference per treated patient and the corresponding difference in mean OS or PFS between everolimus and each comparator. One-way sensitivity analyses were conducted by varying efficacy and cost inputs. RESULTS: Compared with everolimus, cabozantinib, nivolumab, and axitinib were associated with 1.6, 0.3, and 0.5 additional months of PFS, respectively, over 1 year. Cabozantinib and nivolumab were associated with additional months of OS compared with everolimus (1 year: 0.7 and 0.8 months; 2 years: 1.6 and 2.3 months; respectively); axitinib was associated with fewer months (1 year: -0.2 months; 2 years: -0.7 months). The additional costs of treatment with cabozantinib, nivolumab, or axitinib versus everolimus over 1 year were $34,141, $19,371, and $17,506 higher, respectively. Everolimus had similar OS and lower costs compared with axitinib. The additional cost per month of OS was $48,773 for cabozantinib and $24,214 for nivolumab versus everolimus. The additional treatment cost with cabozantinib, nivolumab, or axitinib versus everolimus for each additional month of PFS was estimated at $21,338, $64,570, and $35,012, respectively. Over 2 years, the additional costs per additional month of OS for nivolumab and axitinib versus everolimus were similar to the 1-year analysis; for cabozantinib, the cost was lower. Results were sensitive to changes in mean OS, mean PFS, therapy duration, and drug costs estimates. CONCLUSIONS: Everolimus for second-line mRCC was associated with similar OS and lower costs compared with axitinib over 1- and 2-year horizons. The additional cost per additional month of OS and PFS associated with cabozantinib or nivolumab versus everolimus creates a metric for evaluating the cost of second-line therapies in relation to their respective treatment effects. DISCLOSURES: Funding for this research was provided by Novartis, which was involved in all stages of study research and manuscript preparation. Ghate and Perez are employees of Novartis and own stock/stock options. Swallow, Messali, McDonald, and Duchesneau are employees of Analysis Group, which has received consultancy fees from Novartis. Study concept and design were contributed by Swallow, Messali, Ghate, and Perez, along with McDonald and Duchesneau. Swallow, Messali, McDonald, and Duchesneau collected the data, and all authors participated in data interpretation. The manuscript was written by Swallow, Messali, and Ghate, along with the other authors, and revised by Swallow, Messali, Ghate, and Perez. A synopsis of the current research was presented in poster format at the 15th International Kidney Cancer Symposium on November 4-5, 2016, in Miami, Florida.

Real-world Effectiveness of Biologic Disease-modifying Antirheumatic Drugs for the Treatment of Rheumatoid Arthritis After Etanercept Discontinuation in the United Kingdom, France, and Germany.

PURPOSE: The purpose of this study was to assess the real-world effectiveness of patients with rheumatoid arthritis (RA) who discontinued etanercept treatment and subsequently received another tumor necrosis factor α (TNF-α) inhibitor or a non-TNF-α biologic in the United Kingdom, France, and Germany. METHODS: Medical record data of patients with RA were collected from a panel of rheumatologists in the United Kingdom, France, and Germany. Patients were required to have a diagnosis of RA, be ≥18 years old, and have initiated use of another TNF-α inhibitor (adalimumab, certolizumab pegol, golimumab, or infliximab) or a non-TNF-α biologic (abatacept or tocilizumab) between January 2014 and May 2015 after discontinuing use of etanercept. Reasons for discontinuing use of etanercept and selecting a second biologic disease-modifying antirheumatic drug (DMARD) were described. Study outcomes included European League Against Rheumatism (EULAR) response and change in Clinical Disease Activity Index (CDAI) score. The study outcomes were compared among treatment groups (ie, TNF-α inhibitors and non-TNF-α biologics) using descriptive and multivariable-adjusted analyses. As a secondary analysis, the study outcomes were also descriptively compared between each of the TNF-α inhibitors. Because adalimumab is one of the most commonly used TNF-α inhibitor to treat RA, a secondary analysis was conducted to compare the outcomes among adalimumab, other TNF-α inhibitors, and non-TNF-α inhibitors. FINDINGS: Patient characteristics before initiating treatment with a second DMARD were similar across treatment groups (all TNF-α inhibitors [n = 296] and non-TNF-α biologics [n = 276]). The most common reasons for discontinuing etanercept treatment were inadequate response, adverse effects, and patient preference. After etanercept, TNF-α inhibitors overall were associated with a significantly lower EULAR good response rate (56.0% vs. 64.4%, P < 0.05) and smaller CDAI score change (-6.3 vs -7.3, P = .06) relative to non-TNF-α biologics. However, the proportion of patients achieving an EULAR good response was numerically higher for adalimumab versus other TNF-α inhibitors (61.1% vs 51.6%, P = 0.11) and comparable versus non-TNF-α biologics (61.1% vs 64.4%, P = 0.52). Adalimumab was also associated with a CDAI score change significantly greater than that of other TNF-α inhibitors (-7.1 vs -5.8, P < 0.05) and comparable to that of non-TNF-α biologics (-7.1 vs -7.3, P = 0.79). The results were consistent in the multivariable-adjusted analysis and secondary analysis. IMPLICATIONS: In this retrospective analysis of patients with RA in the United Kingdom, France, and Germany, after discontinuation of etanercept treatment, TNF-α inhibitors as a class were overall less effective as second biologic DMARDs relative to non-TNF-α biologics; however, adalimumab was more or as effective as other TNF-α inhibitors and non-TNF-α biologics.

Cost-Effectiveness Analysis of Isavuconazole vs. Voriconazole as First-Line Treatment for Invasive Aspergillosis.

INTRODUCTION: Invasive aspergillosis (IA) is associated with a significant clinical and economic burden. The phase III SECURE trial demonstrated non-inferiority in clinical efficacy between isavuconazole and voriconazole. No studies have evaluated the cost-effectiveness of isavuconazole compared to voriconazole. The objective of this study was to evaluate the costs and cost-effectiveness of isavuconazole vs. voriconazole for the first-line treatment of IA from the US hospital perspective. METHODS: An economic model was developed to assess the costs and cost-effectiveness of isavuconazole vs. voriconazole in hospitalized patients with IA. The time horizon was the duration of hospitalization. Length of stay for the initial admission, incidence of readmission, clinical response, overall survival rates, and experience of adverse events (AEs) came from the SECURE trial. Unit costs were from the literature. Total costs per patient were estimated, composed of drug costs, costs of AEs, and costs of hospitalizations. Incremental costs per death avoided and per additional clinical responders were reported. Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted. RESULTS: Base case analysis showed that isavuconazole was associated with a $7418 lower total cost per patient than voriconazole. In both incremental costs per death avoided and incremental costs per additional clinical responder, isavuconazole dominated voriconazole. Results were robust in sensitivity analysis. Isavuconazole was cost saving and dominant vs. voriconazole in most DSA. In PSA, isavuconazole was cost saving in 80.2% of the simulations and cost-effective in 82.0% of the simulations at the $50,000 willingness to pay threshold per additional outcome. CONCLUSION: Isavuconazole is a cost-effective option for the treatment of IA among hospitalized patients. FUNDING: Astellas Pharma Global Development, Inc.

The Long-Term Benefits of Increased Aspirin Use by At-Risk Americans Aged 50 and Older.

BACKGROUND: The usefulness of aspirin to defend against cardiovascular disease in both primary and secondary settings is well recognized by the medical profession. Multiple studies also have found that daily aspirin significantly reduces cancer incidence and mortality. Despite these proven health benefits, aspirin use remains low among populations targeted by cardiovascular prevention guidelines. This article seeks to determine the long-term economic and population-health impact of broader use of aspirin by older Americans at higher risk for cardiovascular disease. METHODS AND FINDINGS: We employ the Future Elderly Model, a dynamic microsimulation that follows Americans aged 50 and older, to project their lifetime health and spending under the status quo and in various scenarios of expanded aspirin use. The model is based primarily on data from the Health and Retirement Study, a large, representative, national survey that has been ongoing for more than two decades. Outcomes are chosen to provide a broad perspective of the individual and societal impacts of the interventions and include: heart disease, stroke, cancer, life expectancy, quality-adjusted life expectancy, disability-free life expectancy, and medical costs. Eligibility for increased aspirin use in simulations is based on the 2011-2012 questionnaire on preventive aspirin use of the National Health and Nutrition Examination Survey. These data reveal a large unmet need for daily aspirin, with over 40% of men and 10% of women aged 50 to 79 presenting high cardiovascular risk but not taking aspirin. We estimate that increased use by high-risk older Americans would improve national life expectancy at age 50 by 0.28 years (95% CI 0.08-0.50) and would add 900,000 people (95% CI 300,000-1,400,000) to the American population by 2036. After valuing the quality-adjusted life-years appropriately, Americans could expect $692 billion (95% CI 345-975) in net health benefits over that period. CONCLUSIONS: Expanded use of aspirin by older Americans with elevated risk of cardiovascular disease could generate substantial population health benefits over the next twenty years and do so very cost-effectively.

Direct and Indirect Costs of Chronic and Episodic Migraine in the United States: A Web-Based Survey.

OBJECTIVE: The objective of this study was to compare the societal direct and indirect costs of chronic and episodic migraine in the United States. BACKGROUND: Episodic and chronic migraine are distinguished by the frequency of headache-days. Chronic migraine has a greater overall impact on quality of life than does episodic migraine. Individuals with chronic migraine also use more healthcare resources (resulting in higher direct costs) and experience greater decreases in productivity (resulting in higher indirect costs) than those with episodic migraine as shown in the American Migraine Prevalence and Prevention (AMPP) Study. METHODS: The International Burden of Migraine Study utilized a web-based questionnaire to elicit data on several topics related to the burden of migraine illness, including health resource utilization and productivity losses. Potential survey participants were identified by Synovate Healthcare (Chicago, IL, USA) from a pool of registered panelists from various countries. The panelists were screened online to determine eligibility and to identify individuals with migraine (episodic or chronic), based on reported symptoms. Participants from the United States were divided into episodic and chronic migraine groups, based on reported headache-day per month frequency. Direct and indirect costs were estimated by applying estimated unit costs to reported headache-related productivity losses and resource use. Costs were compared between participants with episodic and chronic migraine. RESULTS: Mean [standard deviation] total annual cost of headache among people with chronic migraine ($8243 [$10,646]) was over three times that of episodic migraine ($2649 [$4634], P < .001). Participants with chronic migraine had significantly greater direct medical costs ($4943 [$6382]) and indirect (lost productivity) costs ($3300 [$6907]) than did participants with episodic migraine (direct, $1705 [$3591]; indirect, $943 [$2084]) (P < .001 for each). Unlike previous findings, direct medical costs constituted the majority of total headache-related costs for both chronic migraine (60.0%, $4943 of $8243) and episodic migraine (64.3%, $1705 of $2649) participants. A large portion of direct medical costs are attributable to pharmaceutical utilization among both chronic migraine (80%, $3925 of 4943) and episodic migraine (70%, $1196 of $1705) participants. CONCLUSION: The results of this study build on previous results of the AMPP Study, demonstrating that headache-related direct, indirect, and total costs are significantly greater among individuals with chronic migraine than with episodic migraine in the United States.

Do Statins Reduce the Health and Health Care Costs of Obesity?

CONTEXT: Obesity impacts both individual health and, given its high prevalence, total health care spending. However, as medical technology evolves, health outcomes for a number of obesity-related illnesses improve. This article examines whether medical innovation can mitigate the adverse health and spending associated with obesity, using statins as a case study. Because of the relationship between obesity and hypercholesterolaemia, statins play an important role in the medical management of obese individuals and the prevention of costly obesity-related sequelae. METHODS: Using well-recognized estimates of the health impact of statins and the Future Elderly Model (FEM)-an established dynamic microsimulation model of the health of Americans aged over 50 years-we estimate the changes in life expectancy, functional status and health care costs of obesity due to the introduction and widespread use of statins. RESULTS: Life expectancy gains of statins are estimated to be 5-6 % greater for obese individuals than for healthy-weight individuals, but most of these additional gains are associated with some level of disability. Considering both medical spending and the value of quality-adjusted life-years, statins do not significantly alter the costs of class 1 and 2 obesity (body mass index [BMI] ≥30 and ≥35 kg/m(2), respectively) and they increase the costs of class 3 obesity (BMI ≥40 kg/m(2)) by 1.2 %. CONCLUSIONS: Although statins are very effective medications for lowering the risk of obesity-associated illnesses, they do not significantly reduce the costs of obesity.

A review of the economic burden of glioblastoma and the cost effectiveness of pharmacologic treatments.

Grade IV glioma (glioblastoma) is one of the most common brain/central nervous system cancers. In 2005, the standard of care for adjuvant treatment was significantly changed with the approval of temozolomide. Carmustine wafers have also gained some popularity. Phase III trials are currently evaluating bevacizumab in conjunction with the standard temozolomide regimen. Despite these recent advances in pharmacotherapy, roughly two-thirds of patients do not survive longer than 2 years after diagnosis. Meanwhile, the costs of treatment are substantial. The goal of this study is to review the clinical, cost-of-illness, and cost-effectiveness literature relevant to treating glioblastoma. Estimates of the economic burden of glioblastoma within different healthcare systems were converted to 2013 US dollars. Temozolomide has demonstrated a 2.5-month increase in overall survival and a 1.9-month increase in progression-free survival, relative to radiotherapy alone. Carmustine wafers have also been shown to increase overall survival by 2.3 months, compared with placebo wafers. Cost-effectiveness studies of temozolomide have produced incremental cost-effectiveness ratios, adjusted to 2013 US dollars, with a range from US$73,586 per quality-adjusted life-year (QALY) (UK National Health Service perspective) to US$105,234 per QALY (US societal perspective). More research is needed to quantify the full societal burden of illness.

Treatment persistence and switching in triptan users: a systematic literature review.

OBJECTIVE: To conduct a systematic review to evaluate persistence to and switching of triptan therapy for the acute treatment of migraine. BACKGROUND: Migraine affects over 12% of adults in Western countries and an estimated 36 million people in the United States. Triptans are an abortive treatment option in patients with moderate to severe migraine. Despite the safety and efficacy of triptans reported in clinical trials, observational studies have consistently demonstrated low persistence to therapy and frequent switching among products over time. METHODS: The following databases were researched: Medline, CENTRAL, and EMBASE. Detailed inclusion and exclusion criteria were specified a priori before conducting abstract and full-text screening. Included studies were required to: (1) report triptan use for migraine treatment; (2) report measures of persistence and/or switching patterns; (3) study migraineurs aged 18 years or older; and (4) conduct an observational study. Studies were excluded if they (1) incorporated interventional study design; (2) lack information or relevance to outcome of interest; (3) were not original research; (4) did not clearly state the results; and (5) were not written in English. Abstracts and full-text articles were reviewed independently by two investigators. RESULTS: Out of 595 studies identified, 380 studies were included for abstract screening. A total of 12 articles met the eligibility criteria after full-text screening of 44 studies, including four studies from reference search. The proportion of patients that remained persistent up to six refills of an index triptan ranged from 3.2% to 12.6% and the proportion of patients that never refilled their index triptan ranged from 38% to 65.8%. In addition to those patients who discontinued, several studies reported that 5-9% of newly initiating triptan users switch to a different triptan before refilling their original medication. Finally, several studies reported the 1-year probability of discontinuation among a general group of triptan users (not limited to treatment naïve patients) to be between 30% and 60%. CONCLUSIONS: Triptans can be a valuable option for acute treatment of migraine. However, studies have shown that treatment persistence is low. This, along with frequent switching behaviors, suggests that a significant unmet clinical need remains despite the wide availability of triptans.

Novel methods of measuring clinical outcomes from psoriasis and psoriatic arthritis clinical trials.

Numerous instruments exist that measure the clinical and health related quality of life impact of psoriasis and psoriatic arthritis (PsA) in clinical trials. However, many of these instruments are not typically used in economic evaluations to inform decision problems facing health care decision makers. This study reviews the current state of psoriasis and PsA health outcome measures and evaluates their limitations in cost-effectiveness analyses (CEAs). We highlight the health related quality of life and clinical outcome measures that are typically used in CEAs, with special focus on studies with quality adjusted life years as a primary outcome measure. Despite the high prevalence of psoriasis and PsA health outcome measures in clinical trials, only a few are used in CEAs. The methods by which utilities are estimated from these measures vary across cost-effectiveness studies. These differences should be considered when conducting cost-effectiveness research in psoriasis and PsA.

Health care resource utilization following initiation of a triptan: a retrospective claims analysis.

BACKGROUND: 23 million Americans suffer from migraine headaches, incurring more than $1 billion in direct medical costs each year (with another $13 billion in indirect productivity losses). Triptans are the most common treatment of choice for these patients; however, adherence and persistence to triptans are poor. Partly due to poor adherence to therapy, the ability of triptans to reduce the utilization of other medical services and prescription drugs remains unclear. OBJECTIVES: To (a) assess changes in the utilization of medical services and relevant prescription drugs after patients suffering from episodic migraines begin triptan therapy and (b) further investigate the relationship between concomitant opioid use among triptan-treated migraine patients and further utilization of medical services and prescription drugs. METHODS: A retrospective analysis of pharmacy and medical insurance claims was carried out using a large and nationally representative database. The utilization patterns of episodic migraine patients were observed for 12 to 24 months prior to their first triptan prescription and 12 to 24 months following that prescription. Resource utilization included physician office visits, diagnostic imaging, emergency room use, inpatient hospitalization, opioid prescriptions, migraine prophylaxis prescriptions, and acetaminophen or nonsteroidal anti-inflammatory prescriptions. Results were stratified according to triptan-switching behavior. RESULTS: The analytic sample included 9,521 migraine patients who were followed for a median of 550 days before and after their first triptan fill. 40.9% of these patients filled their triptan prescriptions only once (index fill). Another 40.3% filled a triptan prescription at least twice and never switched their triptan brand. 15.6% of patients switched their triptan prescriptions once, and 3.2% of patients switched their triptan prescriptions twice or more. The only group to display significant reductions in resource utilization following the prescription of a triptan was the cohort that never refilled the medication, potentially suggestive of misdiagnosis. Either no significant change or a significant increase in resource utilization was seen in all other cases. The ability of triptans to reduce resource utilization seemed to be lower among patients who switched triptans more often. Patients that concomitantly used opioid medications in addition to triptans also used significantly more resources than migraine patients who were not treated with opioids. CONCLUSION: Contrary to the findings of some previous research, the initiation of triptan therapy did not significantly reduce the utilization of migraine-related medical services or other relevant prescription drugs in this retrospective claims analysis. This may have been due to higher and more realistic rates of triptan switching and discontinuation. Consistent with previous findings, patients using concomitant opioids used more migraine-related health care resources.

Cost effectiveness of moderate to severe psoriasis therapy with etanercept and ustekinumab in the United States.

BACKGROUND: Limited information is available on the cost effectiveness of ustekinumab and alternative biologic treatments in a United States (US) setting. Given the recent head-to-head clinical trial study of ustekinumab and etanercept, an economic model comparing the two treatments can be constructed. Etanercept and ustekinumab are indicated for the treatment of chronic moderate to severe plaque psoriasis in adult patients who are candidates for phototherapy or systemic therapy. OBJECTIVE: Clinical trials have evaluated the efficacy of ustekinumab, an anti-cytokine biologic, for the treatment of moderate to severe psoriasis. This study evaluated the cost effectiveness of ustekinumab compared with etanercept from a US societal perspective. METHODS: A Markov model was constructed to simulate the incremental cost per quality-adjusted life-year (QALY) gained every 12 weeks over a base-case 3-year time horizon. A hypothetical patient cohort was based on the characteristics of the phase III Active Comparator Psoriasis Trial (ACCEPT). The main outcome measures were costs and QALYs, which were estimated from the US societal perspective. Costs, utilities, treatment strategy, and resource use estimates were obtained from relevant literature. All costs were adjusted to 2011 US dollars. A 3 % annual discount rate was applied to costs and QALYs. Incremental cost-effectiveness ratios were in US dollars per QALY gained. RESULTS: For the base-case 3-year time horizon, the incremental cost-effectiveness ratio comparing ustekinumab 90 mg with etanercept 50 mg was US$384,401 per QALY gained. Ustekinumab 45 mg dominates etanercept 50 mg for the same time horizon. These results were robust to sensitivity analyses involving treatment strategy, transition probabilities, valuing outcomes, and resource use and costs. The probabilistic sensitivity analysis suggests ustekinumab 90 mg has a minimal (4 %) chance of being cost effective compared with etanercept 50 mg at a willingness-to-pay threshold of US$150,000 per QALY improvement. For the same threshold, ustekinumab 45 mg has a high (88 %) chance of being cost effective compared with etanercept 50 mg. CONCLUSION: Under typical US willingness-to-pay cutoffs, ustekinumab 90 mg is not cost effective compared with etanercept 50 mg therapy in moderate to severe psoriasis patients for the base-case 3-year time horizon. Ustekinumab 45 mg dominates etanercept 50 mg therapy for an equivalent patient psoriasis severity and time horizon.

The cost-effectiveness of temozolomide in the adjuvant treatment of newly diagnosed glioblastoma in the United States.

BACKGROUND: The objective of this work was to determine the cost-effectiveness of temozolomide compared with that of radiotherapy alone in the adjuvant treatment of newly diagnosed glioblastoma. Temozolomide is the only chemotherapeutic agent to have demonstrated a significant survival benefit in a randomized clinical trial. Our analysis builds on earlier work by incorporating caregiver time costs and generic temozolomide availability. It is also the first analysis applicable to the US context. METHODS: A systematic literature review was conducted to collect relevant data. Transition probabilities were calculated from randomized controlled trial data comparing temozolomide plus radiotherapy with radiotherapy alone. Direct costs were calculated from charges reported by the Mayo Clinic. Utilities were obtained from a previous cost-utility analysis. Using these data, a Markov model with a 1-month cycle length and 5-year time horizon was constructed. RESULTS: The addition of brand Temodar and generic temozolomide to the standard radiotherapy regimen was associated with base-case incremental cost-effectiveness ratios of $102 364 and $8875, respectively, per quality-adjusted life-year. The model was most sensitive to the progression-free survival associated with the use of only radiotherapy. CONCLUSIONS: Both the brand and generic base-case estimates are cost-effective under a willingness-to-pay threshold of $150 000 per quality-adjusted life-year. All 1-way sensitivity analyses produced incremental cost-effectiveness ratios below this threshold. We conclude that both the brand Temodar and generic temozolomide are cost-effective treatments for newly diagnosed glioblastoma within the US context. However, assuming that the generic product produces equivalent quality of life and survival benefits, it would be significantly more cost-effective than the brand option.