Cost effectiveness and impact on quality of life of abobotulinumtoxinA and onabotulinumtoxinA in the treatment of children with lower limb spasticity in Canada.

Background: Injectable botulinum neurotoxins are a mainstay of treatment for pediatric spasticity. AbobotulinumtoxinA and onabotulinumtoxinA are both injectable toxin therapies used to treat pediatric lower limb (PLL) spasticity in Canada. The objective of this study was to assess the cost-effectiveness of abobotulinumtoxinA vs. onabotulinumtoxinA in the treatment of PLL spasticity in Canada.Methods: A probabilistic Markov cohort model with a 2-year time horizon was developed, with health states defined by response to therapy, as characterized by the goal attainment scale (GAS). Based on randomized controlled trial evidence, response to therapy was similar or higher for abobotulinumtoxinA relative to onabotulinumtoxinA; uncertainty was incorporated into model parameters, however, as the two therapies have not been compared head-to-head. Canadian resource use and cost data were incorporated.Results: In the base case, abobotulinumtoxinA generated 1.48 quality-adjusted life years over the model time horizon, compared to 1.47 for onabotulinumtoxinA. AbobotulinumtoxinA was associated with cost savings of $123 CAD, reflecting lower costs in both medication acquisition and health services. The estimated improvement to quality of life and reduced costs result in an estimate of economic dominance for abobotulinumtoxinA over onabotulinumtoxinA. This dominant result persisted across probabilistic and scenario analyses.Key points for decision makersBased on a review of available clinical evidence, abobotulinumtoxinA was found to have significant and/or numerical efficacy benefits to onabotulinumtoxinA on functional outcomes (Goal Attainment Scale) and tone (Modified Ashworth Scale) and in the treatment of pediatric lower limb spasticityIn this cost-effectiveness analysis, abobotulinumtoxinA was found to be associated with greater quality-adjusted life years and lower costs than onabotulinumtoxinA (economically dominant)A limitation of this analysis was the uncertainty around key parameters. Specifically, the lack of head-to-head comparison data for the two therapies, and variable data regarding likely onabotulinumtoxinA dosing in PLL in clinical practice. However, across a range of plausible scenarios, the economic dominant result remained.

Cost-of-illness of metastatic gastroenteropancreatic neuroendocrine tumours in Sweden-A population-based register-linkage study.

The objective was to estimate the cost-of-illness of grades 1 and 2 metastatic gastroenteropancreatic neuroendocrine tumours (GEP-NETs) in Sweden in 2013 in a population-based study including all patients diagnosed between 2005 and 2013. Data were obtained from national registers, and patients who utilised healthcare resources due to metastatic GEP-NETs in 2013 were included. The study included 478 patients (mean age 64 [SD=11] years, 51% men). The majority (80%) had small intestinal NET, 10% had pancreatic NET, and 41% had carcinoid syndrome. The total cost-of-illness was €12,189,000 in 2013, of which direct costs constituted 77% and costs from production loss constituted 22%. The largest contributor to the direct medical costs was prescription drugs (54%; primarily somatostatin analogues [91% of the total drug cost]). Production loss due to sickness absence constituted 52% of the total costs of production loss. The total annual cost per patient was €25,500. By patient group, the cost was €24,800 (95% CI €21,600-€28,100) for patients with small intestinal NET, €37,300 (95% CI €23,300-€51,300) for those with pancreatic NET and €18,600 (95% CI €12,600-€24,500) for patients with other GEP-NETs. To conclude, the total annual cost of grades 1 and 2 metastatic GEP-NETs in Sweden was €25,500 per patient and year.

Cost-effectiveness comparison of cabozantinib with everolimus, axitinib, and nivolumab in the treatment of advanced renal cell carcinoma following the failure of prior therapy in England.

PURPOSE: The aim of this study was to compare the cost-effectiveness of cabozantinib with the standard of care in England in adult patients with advanced renal cell carcinoma (aRCC), following prior vascular endothelial growth factor receptor (VEGFR)-targeted therapy. METHODS: We developed a partitioned-survival model with three health states to assess the cost-effectiveness of cabozantinib and its comparators. The model time horizon was 30 years. Efficacy and safety data were derived from pivotal clinical trials (METEOR: NCT01865747, CheckMate025: NCT01668784, and AXIS: NCT00678392). METEOR data were used for a direct comparison of cabozantinib and everolimus. Cabozantinib and nivolumab were compared indirectly, whereas equal efficacy for axitinib and everolimus was assumed based on a previously published expert opinion. For all efficacy endpoints, the best-fitting log-logistic or fractional polynomial curves were used to estimate outcomes. Utilities were converted from the 5-level EQ-5D version instrument applied during the METEOR study for specific health states. Reductions in utility scores due to adverse events were applied. English costs (eg, drug prices) and resource use (eg, visit to consultant) data were used. RESULTS: The total treatment cost was estimated to be 84,136 Great British Pounds (GBP) per patient treated with cabozantinib. The health gains were 2.26 life-years (LYs) and 1.78 quality-adjusted LYs (QALYs). The incremental cost-effectiveness ratios (ICERs) versus axitinib and everolimus were 98,967 GBP/QALY and 137,450 GBP/QALY, respectively. Cabozantinib was less costly and more effective than nivolumab; the incremental cost was -6,742 GBP and the QALY difference was 0.18. CONCLUSION: Treatment with cabozantinib was more effective than treatment with axitinib or everolimus but was associated with higher total costs. When compared with nivolumab, cabozantinib represents an efficient option with nominally better efficacy and lower costs.

A retrospective study to assess resource utilization and costs in patients with post-stroke spasticity in the United Kingdom.

OBJECTIVE: Post-stroke spasticity (PSS) is a common complication following stroke. This study describes the differences in healthcare resource utilization between patients who do and do not develop PSS in the UK. METHODS: Adults registered in The Health Improvement Network database with a recorded stroke between 2007 and 2011 were included. PSS was identified through Read codes; machine learning was used to retrospectively identify unrecorded PSS events. Patients with diagnosed or predicted PSS in the 12 months after stroke were matched to those with no PSS on age, sex, number of strokes, socioeconomic status, and comorbidities using the nearest neighbor algorithm. Utilization and costs associated with general practitioner visits, nurse visits, hospitalizations, referrals to specialists, laboratory tests, and medications in the 12 months after stroke were compared. RESULTS: Overall, 2,951 PSS cases were matched to 37,753 controls. During the first year, more PSS cases visited a physiotherapist (19% vs 7%) and occupational therapist (12% vs 5%) compared to controls. A greater proportion of cases were also referred to specialists (76% vs 64%) and hospitalized (33% vs 9%) compared to controls. Medication for spasticity was, on average, 14.68 prescriptions for cases and 5.64 for controls. Total mean costs per patient were £1,270 (standard deviation [SD] = 772) and £635 (SD = 273) for cases and controls, respectively. CONCLUSION: Costs after stroke for patients developing PSS are twice as high compared to patients who do not develop it, with the major driver being the number of hospital admissions. This highlights the need for better recording and closer management of PSS.

Cost-effectiveness analysis of abobotulinumtoxinA for the treatment of cervical dystonia in the United Kingdom.

BACKGROUND: Cervical dystonia (CD) involves painful involuntary contraction of the neck and shoulder muscles and abnormal posture in middle-aged adults. Botulinum neurotoxin type A (BoNT-A) is effective in treating CD but little is known about its associated cost-effectiveness. OBJECTIVE: To evaluate the cost-effectiveness of abobotulinumtoxinA for treating CD from the UK payer perspective. METHODS: A Markov model was developed to evaluate the cost-effectiveness of abobotulinum-toxinA versus best supportive care (BSC) in CD, with a lifetime horizon and health states for response, nonresponse, secondary nonresponse, and BSC in patients with CD (mean age: 53 years; 37% male). Clinical improvement measured using Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) was mapped to utility using data from a randomized trial of abobotulinumtoxinA. Health care resource use, costs, and other inputs were from the British National Formulary, Personal Social Services Research Unit, published literature, or expert opinion. Costs and outcomes were discounted at 3.5% per annum. RESULTS: In the base case, the incremental lifetime quality-adjusted life-years (QALYs) gained from abobotulinumtoxinA arm versus BSC was 0.253 per patient, whereas the incremental cost was £7,160, leading to an incremental cost-effectiveness ratio (ICER) of £30,468 per QALY. One-way sensitivity analyses showed that these results were sensitive to the proportion of responders to abobotulinumtoxinA at first injection, duration between injections, the number of reinjections allowed among primary nonresponders, and any difference in baseline TWSTRS value between the BSC and abobotulinumtoxinA arms. Probabilistic sensitivity analysis showed that abobotulinumtoxinA was cost-effective 46% and 49% of times at thresholds of £20,000 and £30,000 per QALY, respectively. Scenarios are considered including vial-sharing, productivity losses, secondary response/nonresponse at subsequent injections, 5-year time horizon, and alternative reinjection intervals for BoNT-As produced ICERs ranging from cost-saving to £40,777 per QALY, versus BSC. CONCLUSION: AbobotulinumtoxinA was found to be cost-effective in treating adults with CD, at acceptable willingness-to-pay thresholds in the UK.

Comorbidities, treatment patterns and cost-of-illness of acromegaly in Sweden: a register-linkage population-based study.

OBJECTIVE: Acromegaly is a complex endocrine disease with multiple comorbidities. Treatment to obtain biochemical remission includes surgery, medical therapy and radiation. We aimed to describe comorbidities, treatment patterns and cost-of-illness in patients with acromegaly in Sweden. DESIGN: A nationwide population-based study. METHODS: Patients with acromegaly were identified and followed in national registers in Sweden. Longitudinal treatment patterns were assessed in patients diagnosed between July 2005 and December 2013. The cost-of-illness during 2013 was estimated from a societal perspective among patients diagnosed between 1987 and 2013. RESULTS: Among 358 patients with acromegaly (48% men, mean age at diagnosis 50.0 (s.d. 15.3) years) at least one comorbidity was reported in 81% (n = 290). The most common comorbidities were hypertension (40%, n = 142), neoplasms outside the pituitary (30%, n = 109), hypopituitarism (22%, n = 80) and diabetes mellitus (17%, n = 61). Acromegaly treatment was initiated on average 3.7 (s.d. 6.9) months after diagnosis. Among the 301 treated patients, the most common first-line treatments were surgery (60%, n = 180), somatostatin analogues (21%, n = 64) and dopamine agonists (14%, n = 41). After primary surgery, 24% (n = 44) received somatostatin analogues. The annual per-patient cost was €12 000; this was €8700 and €16 000 if diagnosed before or after July 2005, respectively. The cost-of-illness for acromegaly and its comorbidities was 77% from direct costs and 23% from production loss. CONCLUSIONS: The prevalence of comorbidity is high in patients with acromegaly. The most common first-line treatment in acromegalic patients was surgery followed by somatostatin analogues. The annual per-patient cost of acromegaly and its comorbidities was €12 000.

AbobotulinumtoxinA in the management of cervical dystonia in the United Kingdom: a budget impact analysis.

BACKGROUND: Cervical dystonia (CD) can be effectively managed by a combination of botulinum neurotoxin A (BoNT-A) and conventional therapy (skeletal muscle relaxants and rehabilitative therapy), but the costs of different interventions in the UK vary. METHODS: A budget impact model was developed from the UK payer perspective with a 5-year time horizon to evaluate the effects of changing market shares of abobotulinumtoxinA, onabotulinumtoxinA, and incobotulinumtoxinA, and best supportive care from the UK payer perspective. Epidemiological and resource use data were retrieved from the published literature and clinical expert opinion. Deterministic sensitivity analyses were performed to determine the parameters most influential on the budgetary findings under base case assumptions. RESULTS: Under base case assumptions, an increased uptake of abobotulinumtoxinA showed an accumulated savings of £2,250,992 by year 5. Treatment per patient per year with onabotulinumtoxinA and incobotulinumtoxinA costs more when compared to treatment with abobotulinumtoxinA. One-way sensitivity analyses showed that the prevalence of CD, dose per injection of each of the BoNT-As, and time to reinjection of incobotulinumtoxinA and abobotulinumtoxinA influenced the base case findings most. CONCLUSION: There is potential for cost savings associated with the greater use of abobotulinumtoxinA rather than other BoNT-A treatments, permitting more patients to benefit more from effective BoNT-A treatment with a fixed budget.

Budget impact analysis of botulinum toxin A therapy for upper limb spasticity in the United Kingdom.

BACKGROUND: Botulinum toxin A (BoNT-A) is an effective treatment for patients with upper limb spasticity (ULS), which is a debilitating feature of upper motor neuron lesions. BoNT-A preparations available in the UK are associated with different costs. METHODS: We developed a budget impact model to assess the effect of changing market shares of different BoNT-A formulations - abobotulinumtoxinA, onabotulinumtoxinA, and incobotulinumtoxinA - and best supportive care, from the UK payer perspective, over a 5-year time horizon. Epidemiological and resource use data were derived from published literature and clinical expert opinion. One-way sensitivity analyses were performed to determine parameters most influential on budget impact. RESULTS: Base-case assumptions showed that an increased uptake of abobotulinumtoxinA resulted in a 5-year savings of £6,283,829. Treatment with BoNT-A costs less than best supportive care per patient per year, although treating a patient with onabotulinumtoxinA (£20,861) and incobotulinumtoxinA (£20,717) cost more per patient annually than with abobotulinumtoxinA (£19,800). Sensitivity analyses showed that the most influential parameters on budget were percentage of cerebral palsy and stroke patients developing ULS, and the prevalence of stroke. CONCLUSION: Study findings suggest that increased use of abobotulinumtoxinA for ULS in the UK could potentially reduce total ULS cost for the health system and society.

A retrospective study to assess resource utilization in patients with cervical dystonia in the United Kingdom.

PURPOSE: Cervical dystonia (CD) is a hypertonic condition caused by damage to the central nervous system. Very few studies have assessed the overall economic burden of the disease. The objective of this study was to describe the utilization of health care resources of patients with CD in the UK primary care setting, using a large population-based database. PATIENTS AND METHODS: Adults with a first diagnosis of CD between January 1, 2007 and January 31, 2011, who were registered to a general practitioner (GP) practice contributing to The Health Improvement Network (THIN), were included. Sociodemographic and clinical characteristics were assessed at the time of diagnosis. Health care resource utilization and pharmacological treatment were investigated at the end of the first and second year after diagnosis. RESULTS: Overall, 4,024 newly diagnosed patients with CD were identified, with average age at diagnosis of 45 years old; 65.3% were female. Depression in the year prior to diagnosis was the most common comorbidity. Primary care utilization was high in the first year, with 99.2% of patients visiting their GP (on average 6.2 times), and 43% visiting a nurse (on average 2.5 times). Patients were most commonly referred to an orthopedic surgeon, and 15.9% reported at least one physiotherapy visit. In the second year, utilization was similar. Prescriptions of at least one of the investigated treatments were found in 82.0% and 45.3%, in the first and second year, respectively. CONCLUSION: Findings suggest a high number of new CD cases are being identified in primary care, but not all will be referred to secondary care. Health care resource utilization was compared with that of all patients registered in THIN, which is representative of the UK, and the adjusted usage of primary care resources was found to be similar to that of the THIN population.

Treatment Patterns and Economic Burden in Patients Treated for Acromegaly in the USA.

BACKGROUND: Acromegaly is a rare, debilitating condition for which data on the associated treatment patterns and economic burden are limited. OBJECTIVE: Our objective was to examine patient characteristics, treatment patterns, and healthcare resource utilization (HRU)/costs for individuals with acromegaly treated with surgical and/or medical therapy in the USA. METHODS: Using a large US claims database, adults with new episodes of acromegaly between 1 July 2007 and 31 December 2010 were identified (the first observed diagnosis being the index date). Patients had 6-month pre-index and 12-month post-index continuous enrollment and surgical and/or medical treatment during the 12-month post-index period. Descriptive analysis was performed to observe demographic/clinical characteristics, treatment patterns, HRU, and monthly healthcare costs between two mutually exclusive surgically and medically treated cohorts. RESULTS: This study included 228 acromegalic individuals treated with surgical therapy and 169 treated with medical therapy. During the 12-month follow-up, compared with the medical cohort, the surgical cohort were more likely to have hypertension (50.4 vs. 32.0 %), sleep apnea (31.6 vs. 15.8 %), cardiac dysrhythmia (16.7 vs. 7.0 %), hospitalizations (98.3 vs. 13.6 %), and emergency room visits (29.8 vs. 20.7 %), and had more outpatient visits (10.2 vs. 5.2) and physician office visits (21.2 vs. 15.0) (all differences, p < 0.05). The surgical cohort had lower monthly healthcare costs during the 6-month pre-index period ($US1963.5 vs. 2818.4) but higher costs in the 12-month post-index period ($US5202.6 vs. 3076.5) than the medical cohort. CONCLUSIONS: Our findings suggest the treatment pathway observed in this patient population has a non-negligible association with the clinical and economic burden.

Assessing the burden of illness from cervical dystonia using the Toronto Western Spasmodic Torticollis Rating Scale scores and health utility: a meta-analysis of baseline patient-level clinical trial data.

PURPOSE: This study aimed to explore the burden of illness associated with cervical dystonia (CD), including possible demographic and humanistic correlates of baseline disease severity. METHODS: The analysis involved the five multinational randomized, placebo-controlled clinical trials that had evaluated the efficacy and safety of Dysport® in patients with CD, including assessment using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Patient-level TWSTRS scores from the individual studies were meta-analysed to estimate disease severity at baseline. One of the studies had reported Short Form-36 (SF-36) Health Survey quality-of-life measures, and these data were used to investigate whether the severity of CD was associated with humanistic outcomes, as measured by health utility. A generalized regression model was then applied to explore potential correlation between TWSTRS scores and utilities. RESULTS: The estimated pooled mean baseline severity of CD in clinical trial entrants, as measured by TWSTRS score, was 43.23 (95% CI = 39.31-47.15). In general, disease severity was significantly greater in patients aged over 40 years (compared to the reference group aged 18-30 years). However, there was no correlation between disease severity and other demographic characteristics (e.g., weight, height, gender). Higher TWSTRS scores correlated with worse health-related quality of life as perceived by patients and was reflected in health utility (R(2 )= 0.133). CONCLUSIONS: This study was able to define TWSTRS scores in patients with CD in terms of associated utility. This approach could help in capturing the disease's burden through measures that are more tangible than TWSTRS scores to patients, carers, clinicians, and healthcare payers.

Epidemiological, humanistic, and economic burden of illness of lower limb spasticity in adults: a systematic review.

BACKGROUND: The purpose of this study was to investigate the epidemiological, humanistic, and economic burden of illness associated with adult lower limb spasticity (LLS) and its complications. METHODS: A systematic search of MEDLINE and EMBASE identified 23 studies published between January 2002 and October 2012 that assessed the epidemiology, impact, and resource use associated with LLS. A hand-search of four neurology conferences identified abstracts published between 2010 and 2012. RESULTS: LLS was found to occur in one third of adults after stroke, half to two thirds with multiple sclerosis, and three quarters with cerebral palsy. LLS limits mobility and reduces quality of life. No clear association was found between LLS and occurrence of pain, development of contractures, or risk of falls. CONCLUSION: The evidence on the burden of LLS and its complications is surprisingly limited given the condition's high prevalence among adults with common disorders, such as stroke. Further research is needed to clarify the impact of LLS, including the likelihood of thrombosis in spastic lower limbs. The dearth of high-quality evidence for LLS suggests a lack of awareness of, and interest in, the problem, and therefore, the unmet need among patients and their carers.

[Cost of obesity in France]. / Evaluation du coût associé à l'obésité en France.

OBJECTIVE: To estimate the costs associated with obesity in France. METHODS: We used data from the 2002 survey on health and social protection as well as health care consumption data from the EPAS sample of the national health insurance funds. After excluding those younger than 18 years, pregnant women and people diagnosed with cancer, we classified subjects as underweight, normal weight, or obese and then studied two subpopulations: (P1) obese patients (body mass index (BMI) >or= 30 kg/m2) and (P2) patients who were obese or overweight (BMI >or= 27 kg/m2) and had additional cardiovascular risk factors: hypertension, dyslipidemia, type 2 diabetes, myocardial infarction (present or history), transient ischemic attack, intermittent claudication or sleep apnea. The Heckman approach was used to adjust for several factors. RESULTS: The study included 4651 individuals, with a mean age was 47 years. The obesity prevalence rate was estimated at 10.7% for P1; the P2 prevalence was 16.0%. Average healthcare costs for the entire study group were 1534 euro, 1105 euro for ambulatory care (72%) and 429 euro (28%) for inpatient care. Costs for obese subjects (P1 and P2) averaged 2500 euro, twice the costs for normal-weight people (1263 euro). After taking into account age, sex, socioeconomic status, alcohol consumption and smoking, the 100% reimbursement rate for chronic diseases (all else being equal), the extra cost of obesity, compared with normal weight, was estimated between 506 euro (P1) and 648 euro (P2). CONCLUSION: The annual total cost of obesity was estimated to range from 2.1 to 6.2 billion euros in 2002 and account for 1.5 to 4.6% of total health expenditures in France.

Insomnia and absenteeism at work. Who pays the cost?

STUDY OBJECTIVE: To estimate the costs of insomnia-associated work absenteeism and to analyze how these costs are shared between the different payers: the national health insurance system, employers, and employees. DESIGN: Retrospective cohort study over a 2-year period. SETTING: The Paris Ile de France region. PATIENTS: Two matched groups of employees: 369 insomniacs and 369 good sleepers. MEASUREMENTS: The costs of absenteeism at work associated with insomnia were estimated by comparing the 2 matched groups in terms of the number and duration of work absences. We considered that work absences incurred costs relating to salary replacement and loss of productivity: these were given a monetary value on the basis of the added value per hour worked. RESULTS: The percentage of employees with at least 1 work absence are 50% and 34% for insomniacs and good sleepers, respectively. The work absenteeism (expressed in days, per employee, per year +/- confidence intervals [CI]) differed significantly between insomniacs and good sleepers: 5.8 (+/- 1.1 ) and 2.4 (+/- 0.5), respectively (p < .001). The extra cost (+/- CI) to the national health insurance system of insomnia-associated absenteeism was estimated at euro 77 (+/- euro 39) per employee, per year. The extra cost (+/- CI) to employers was estimated at euro 233 (+/- euro 101) for salary replacement and euro 1062 (+/- euro 386) for loss of productivity. Finally, employees themselves bore a cost (+ CI) of euro 100 (euro 54). CONCLUSIONS: Employees who suffered from insomnia had a significantly higher rate of absenteeism at work than those who slept well. This absence represents a cost for society: in France, 88% of this amount is shouldered by employers.

The comparative medical costs of atherothrombotic disease in European countries.

BACKGROUND: The clinical manifestations of atherothrombotic disease include ischaemic heart disease (including myocardial infarction [MI]) and cerebrovascular disease (including ischaemic stroke [IS]). Although costs generated by the clinical manifestations of atherothrombotic disease represent an important economic burden for any healthcare system, very few economic comparative data are available. OBJECTIVE: To: (i) assess management costs of the different practice patterns for acute and chronic phases for MI, IS and peripheral arterial disease (PAD) in eight European countries; and (ii) to simulate the cost of managing a patient with an atherothrombotic disease for 2 years in Europe. STUDY PERSPECTIVE: Healthcare system. METHODS: Firstly, the medical costs of managing MI and IS were analysed during the acute phase and subsequent 6-month periods over a total of 2 years. In each case, a decision tree was designed to indicate resource use. Assumptions concerning patient management and resource use were based on currently available local and international literature, official national statistics and local expert opinions (Delphi panel). Costs were assessed using diagnosis-related groups (Austria, Italy, Portugal and Sweden), or hospital databases and national tariffs (Belgium, France, Spain and Switzerland). Secondly, these costs were correlated to data from a large randomised clinical trial to estimate the overall cost per patient with atherothrombotic disease over a 2-year period. RESULTS: For MI, there was a 2-fold difference in costs between the eight countries (euro9512-18 293), with 47-76% of costs devoted to acute management, 14-48% to follow-up management during the first year, and 4-17% to follow-up during the second year. For IS, there was a 10-fold difference (euro5607-56 370), with 18-75% devoted to follow-up for the years 1995-1997. CONCLUSIONS: There are differences in the overall costs and cost breakdown in the clinical management patterns of MI and IS in Europe. These differences seem to arise as a result of local treatment pattern specificities as well as the availability of specific and well-adapted structures for patients' rehabilitation. Further studies are necessary to fully explain these differences. The assessment of the total medical costs of managing an atherothrombotic patient over a 2-year period (MI, IS, established PAD) has to take into account the risk of ischaemic events in different vascular areas (MI, IS or major leg ischaemia).