Pharmaceutical Treatment for Alzheimer's Disease and Related Dementias: Utilization and Disparities.

BACKGROUND: Four prescription drugs (donepezil, galantamine, memantine, and rivastigmine) are approved by the US FDA to treat symptoms of Alzheimer's disease (AD). Even modest effectiveness could potentially reduce the population-level burden of AD and related dementias (ADRD), especially for women and racial/ethnic minorities who have higher incidence of ADRD. OBJECTIVE: Describe the prevalence of antidementia drug use and timing of initiation relative to ADRD diagnosis among a nationally representative group of older Americans, and if there are disparities in prevalence and timing by sex and race/ethnicity. METHODS: Descriptive analyses and logistic regressions of Medicare claims (2008-2016) for beneficiaries who had an ADRD or dementia-related symptom diagnosis, or use of an FDA approved drug for AD. We investigate prevalence of use and timing of treatment initiation relative to ADRD diagnosis across time and beneficiary characteristics (age, sex, race/ethnicity, socioeconomic status, comorbidities). RESULTS: Among persons diagnosed with ADRD or related symptoms, 33.3% used an approved drug over the study period. Odds of use was higher among Whites than non-Whites. Among ADRD drug users, 40% initiated use within 6 months of the initial ADRD or related symptoms diagnosis, and 16% initiated prior to a diagnosis. We observed disparities by race/ethnicity: 28% of Asians, 24% of Hispanics, 16% of Blacks, and 15% of Whites initiated prior to diagnosis. CONCLUSIONS: The use of antidementia drugs is relatively low and varies widely by race/ethnicity. Heterogeneity in timing of initiation and use may affect health and cost outcomes, but these effects merit further study.

Medical Resource Value Appraisal for Leucojum aestivum in Turkey.

In this study, we investigate the medical and economical value of Leucojum aestivum. Leucojum aestivum contains the alkaloid galanthamine, which is one of the main active substances in Reminyl, a commonly used drug for the treatment of Alzheimer's disease (AD). In this analysis, we estimate that there are 13 million mild to moderate patients with Alzheimer's who use Reminyl. Our results suggest that the market change value of L aestivum required for 1 unit of Reminyl is US$62. The value of total change of galanthamine and L aestivumis estimated to be US$18.6 billion per year. Alzheimer's drugs that use L aestivum are relatively expensive, ranging in cost from US$183 to more than US$400 per month. The minimum annual cost of this is US$2196 per person for "patients with mild and moderate stage AD." The using value of 6 million units of L aestivum bulbs, which is the amount exported from Turkey, is estimated to be US$27 million per year. The determined value for L aestivum is equivalent to the value of a rare flower that can be used to treat the serious illness of AD.

The effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease (review of Technology Appraisal No. 111): a systematic review and economic model.

BACKGROUND: Alzheimer's disease (AD) is the most commonly occurring form of dementia. It is predominantly a disease of later life, affecting 5% of those over 65 in the UK. OBJECTIVES: Review and update guidance to the NHS in England and Wales on the clinical effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine [acetylcholinesterase inhibitors (AChEIs)] and memantine within their licensed indications for the treatment of AD, which was issued in November 2006 (amended September 2007 and August 2009). DATA SOURCES: Electronic databases were searched for systematic reviews and/or metaanalyses, randomised controlled trials (RCTs) and ongoing research in November 2009 and updated in March 2010; this updated search revealed no new includable studies. The databases searched included The Cochrane Library (2009 Issue 4, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials), MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, PsycINFO, EconLit, ISI Web of Science Databases--Science Citation Index, Conference Proceedings Citation Index, and BIOSIS; the Centre for Reviews and Dissemination (CRD) databases--NHS Economic Evaluation Database, Health Technology Assessment, and Database of Abstracts of Reviews of Effects. REVIEW METHODS: The clinical effectiveness systematic review was undertaken following the principles published by the NHS CRD. We included RCTs whose population was people with AD. The intervention and comparators depended on disease severity, measured by the Mini Mental State Examination (MMSE). INTERVENTIONS: mild AD (MMSE 21-26)--donepezil, galantamine and rivastigmine; moderate AD (MMSE 10-20)--donepezil, galantamine, rivastigmine and memantine; severe AD (MMSE < 10)--memantine. Comparators: mild AD (MMSE 21-26)--placebo or best supportive care (BSC); moderate AD (MMSE 10-20)--donepezil, galantamine, rivastigmine, memantine, placebo or BSC; severe AD (MMSE < 10)--placebo or BSC. The outcomes were clinical, global, functional, behavioural, quality of life, adverse events, costs and cost-effectiveness. Where appropriate, data were pooled using pair-wise meta-analysis, multiple outcome measures, metaregression and mixedtreatment comparisons. The decision model was based broadly on the structure of the three-state Markov model described in the previous technology assessment report, based upon time to institutionalisation, parameterised with updated estimates of effectiveness, costs and utilities. RESULTS: Notwithstanding the uncertainty of our results, we found in the base case that the AChEIs are probably cost saving at a willingness-to-pay (WTP) of £'30,000 per qualityadjusted life-year (QALY) for people with mild-to-moderate AD. For this class of drugs, there is a > 99% probability that the AChEIs are more cost-effective than BSC. These analyses assume that the AChEIs have no effect on survival. For the AChEIs, in people with mild to moderate AD, the probabilistic sensitivity analyses suggested that donepezil is the most cost-effective, with a 28% probability of being the most cost-effective option at a WTP of £'30,000 per QALY (27% at a WTP of £'20,000 per QALY). In the deterministic results, donepezil dominates the other drugs and BSC, which, along with rivastigmine patches, are associated with greater costs and fewer QALYs. Thus, although galantamine has a slightly cheaper total cost than donepezil (£'69,592 vs £'69,624), the slightly greater QALY gains from donepezil (1.616 vs 1.617) are enough for donepezil to dominate galantamine.The probability that memantine is cost-effective in a moderate to severe cohort compared with BSC at a WTP of £'30,000 per QALY is 38% (and 28% at a WTP of £'20,000 per QALY). The deterministic ICER for memantine is £'32,100 per/QALY and the probabilistic ICER is £'36,700 per/QALY. LIMITATIONS: Trials were of 6 months maximum follow-up, lacked reporting of key outcomes, provided no subgroup analyses and used insensitive measures. Searches were limited to English language, The model does not include behavioural symptoms and there is uncertainty about the model structure and parameters. CONCLUSIONS: The additional clinical effectiveness evidence identified continues to suggest clinical benefit from the AChEIs in alleviating AD symptoms, although there is debate about the magnitude of the effect. Although there is also new evidence on the effectiveness of memantine, it remains less supportive of this drug's use than the evidence for AChEIs. The conclusions concerning cost-effectiveness are quite different from the previous assessment. This is because both the changes in effectiveness and costs between drug use and non-drug use underlying the ICERs are very small. This leads to highly uncertain results, which are very sensitive to change. RESEARCH PRIORITIES: RCTs to include mortality, time to institutionalisation and quality of life, powered for subgroup analysis. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Economic evaluation of treatment options in patients with Alzheimer's disease: a systematic review of cost-effectiveness analyses.

INTRODUCTION: Alzheimer's disease (AD) is common among the elderly; it is responsible for 60-80% of all dementia cases. AD is characterized by cognitive decline, behavioural and psychological symptoms, and reductions in functioning and independence. Because of its progressive neurodegenerative nature and unknown aetiology, the burden of AD becomes increasingly significant in an aging population. Estimates indicate that 35.6 million people worldwide suffered from AD in 2010. By 2030 and 2050, this figure is predicted to increase to 65.7 million and 115.4 million, respectively. Costs will also rise along with the increase in the number of people diagnosed with AD. In 2010, the worldwide costs associated with dementia were estimated to be $US604 billion. OBJECTIVE: The objective of this study was to conduct a systematic review of current publications dealing with the pharmacoeconomic factors associated with AD medications and to describe the decision-analytic models used to evaluate long-term outcomes. METHODS: A systematic literature search was performed to identify articles published between 1 January 2007 and 15 July 2010. The search was also based on a previous systematic review, which included literature up to 2007. Articles were included if they were complete and original economic evaluations of AD and if they were comparative in nature. A quality assessment of the included publications was conducted and relevant information was extracted into tables. RESULTS: Seven out of 2067 identified articles were included in this systematic review. Four articles evaluated treatment with donepezil, one with galantamine and two with memantine. The studies were conducted in America, Europe and Asia. Five different groups of medications were compared. The incremental cost-effectiveness ratios (ICERs) for the group of patients treated with donepezil versus no drug treatment ranged from a dominant value to 281, 416.13 euros per quality-adjusted life-year (QALY). Patients treated with donepezil versus placebo showed ICERs with a range from a dominant value (not specified) up to 20, 866.77 euros per QALY. Treatment with memantine in addition to donepezil versus treatment with donepezil alone showed an ICER range from a dominant value to 6818.33 euros per QALY. In comparison with the memantine treatment as an add-on therapy, the ICER of memantine monotherapy versus standard care (without cholinesterase inhibitors [CEIs]) ranged from a dominant value to 63, 087.20 euros per QALY. Finally, the economic evaluation of galantamine in comparison with usual care without any AD drugs showed ICERs ranging from 1894.70 euros to 6953 euros per QALY. CONCLUSION: The seven identified publications included in this review indicate that treatment with CEIs or memantine seems to be reasonable in terms of clinical effects and costs for patients with AD. Depending on different hypotheses, assumptions and variables (e.g. time horizon, discount rates, initial number of patients in different states, etc.) in the sensitivity analyses, treatment with these drugs seems to be primarily a cost-effective strategy or even a cost-saving strategy. Nevertheless, the results generally are associated with a degree of uncertainty. The comparability of the results from the different economic evaluations is limited because of the different assumptions made.

The economic impact of galantamine vs placebo: an analysis based on functional capacity in a Swedish cohort study.

OBJECTIVE: To analyse the economic impact of galantamine, based on basic activities of daily living (ADL). METHODS: Data were derived from Swedish patients enrolled in a 6-month placebo-controlled trial of galantamine (GAL-INT-1; n=80), and from the Kungsholmen-Nordanstig Project, a longitudinal study of 919 elderly persons in Sweden. Basic ADL were assessed using the Katz' Index of Independence in Activities of Daily Living (ADL) (number of ADL lost [dependency in 0, 1-2, 3-4, or 5-6 ADL]). Costs were appraised based on regression analysis and on costs directly linked to ADL. Six-month costs for galantamine and placebo were calculated. RESULTS: In the regression analyses, each increase in a Katz stage was associated with an annual cost increase of SEK 81,415-83,683 (∼€8000). Results were similar using stage-specific costs. Overall, there was a small, non-significant numerical cost benefit for galantamine indicating cost neutrality. LIMITATIONS: The small number of Swedish patients in the GAL-INT-1 study, which was not powered for economic outcomes, limits the statistical power of the analysis. In addition, long-term outcomes are difficult to assess in persons with dementia because of practical and logistical problems. CONCLUSIONS: The benefits of galantamine in patients with AD can be achieved with no increase in cost. Combined with positive effects in terms of outcome, treatment with galantamine can be regarded as cost-effective using a cost-consequence approach.

The costs of Alzheimer's disease and the value of effective therapies.

Every 69 seconds, a person in the United States develops Alzheimer's disease (AD). By 2050, this rate is expected to double. Total direct costs of AD and dementia (AD/D) are estimated at $183 billion, and are expected to increase to $1.1 trillion by 2050. In 2010, unpaid care was valued at an estimated $202 billion. Caregivers of patients with AD are usually family members, and provide up to 70 hours of care per week. By delaying institutionalization of an AD patient, a savings of $2029 per month in direct healthcare costs could be realized; therefore, caregiver support is a significant factor in controlling costs. It is important for those with AD/D to have prescription plans that optimize access to AD/D therapies. Among older adults who previously did not have prescription coverage, 80% are now enrolled in Medicare Part D. Three preferred AD/D agents (donepezil, extended release galantamine hydrochloride, and memantine hydrochloride) have been identified by an expert panel. It is important, given the clinical course of AD, especially with progression to moderate-to-severe disease, that physicians continue to have access to preferred medications as demonstrated through evidence-based clinical evaluations. Many Medicare Part D beneficiaries are subject to a gap in prescription coverage known as the "donut hole," including 64% of patients with AD. Because of the increased out-of-pocket expenditures associated with this coverage gap, some patients stop taking their medication completely or reduce medication use. It is critical to avoid lapses in maintenance therapy, as functional and cognitive abilities cannot be regained. Numerous clinical trials have demonstrated the pharmacoeconomic benefits of appropriate and preferred AD therapies; greater therapeutic availability may lead to better adherence and therefore improved outcomes.

Modelling the clinical and economic implications of galantamine in the treatment of mild-to-moderate Alzheimer's disease in Germany.

OBJECTIVE: This analysis was to assess the long-term clinical and economic implications of galantamine in the treatment of mild-to-moderate Alzheimer's disease (AD) in Germany. METHODS: An economic model was developed using discrete event simulation to predict the course of AD through changes in cognition, behavioural disturbance, and function over time. It compares the costs and benefits of galantamine versus no-drug treatment and ginkgo biloba. Clinical data were mainly derived from analyses of pooled data from clinical trials. Epidemiological and cost data were obtained from literature and public data sources. Costs (2009 euros) from the perspective of the German Statutory Health Insurance were used. RESULTS: The mean survival time for the model population is about 3.44 years over 10 years of simulation. Galantamine delays average time to severe stage of the disease by 3.57 and 3.36 months, compared to no-drug treatment and ginkgo biloba, respectively. Galantamine reduces time spent in an institution by 2.34 and 2.21 months versus no-drug treatment and ginkgo biloba, respectively. The use of galantamine is projected to yield net savings of €3,978 and €3,972 per patient versus no-drug and ginkgo biloba treatments. These results, however, may be limited by lack of long-term comparative efficacy data as well as data on long-term care costs based on multiple outcome measures. CONCLUSION: Compared to no-drug treatment and ginkgo biloba, galantamine therapy provides clinical benefits and achieves savings in healthcare costs associated with care for patients with mild-to-moderate AD in Germany.

Prescribing of drugs for Alzheimer's disease: a South African database analysis.

BACKGROUND: Relatively few studies of mental illness in Africa have focused on dementia. The primary aim of this study was to determine the prescribing patterns and cost of drugs for Alzheimer's disease in a private health care sector patient population. METHODS: A retrospective, exposure-cohort pharmacoepidemiological study was conducted. Data were obtained from a South African private pharmacy group for 2008. The database consisted of 1,578,346 medicine records. RESULTS: A total of 588 patients (326 females and 262 males) received 2623 medicine items for Alzheimer's disease at a cost of R1,563,701.18 (average cost per item R596.15). The average age of the patients was 75.54 (SD = 10.48) years. Donepezil was the most frequently prescribed active ingredient (37.09%), followed by galantamine (36.94%). Donepezil accounted for 39.50% of the cost of Alzheimer medication. The average cost per prescription was R634.76 for donepezil and R551.35 for memantine. Only 5.27% of patients were prescribed more than one active ingredient for Alzheimer's disease during the year (mostly donepezil or galantamine, and memantine). Average prescribed daily doses (PDDs) of all active ingredients were generally lower than their respective defined daily doses (DDDs). The average PDD for donepezil was 7.45 mg (DDD = 7.5 mg), for galantamine 13.56 mg (DDD = 16 mg), for memantine 17.46 mg (DDD = 20 mg) and for rivastigmine 6.89 mg (DDD = 9 mg). CONCLUSIONS: A small number of patients were prescribed medicine for Alzheimer's disease. It is recommended that qualitative studies be undertaken to determine the cost-effectiveness of the different treatment options according to family members and carers.

International price comparisons of Alzheimer's drugs: a way to close the affordability gap.

BACKGROUND: Alzheimer's drugs are believed to have limited availability and to be unaffordable in low- and middle-income countries compared to high-income countries. The price, availability and affordability of Alzheimer's drugs have not been reported before. METHODS: During 2007 an international survey was conducted in 21 countries in six continents (Argentina, Australia, Brazil, the Dominican Republic, France, India, Japan, Macedonia, Mexico, New Zealand, Nigeria, the Philippines, Portugal, Serbia, South Korea, Switzerland, Taiwan, Thailand, Uganda, the U.K. and the U.S.A.). Prices of Alzheimer's drugs were compared using the affordability index (the total number of units purchasable with one's daily income) derived from purchasing power parity (PPP) converted prices as well as raw prices. RESULTS: Donepezil is available in all 21 countries, whereas the newer drugs are less available. A 5 mg tablet of branded originator donepezil costs just US$0.26 in India and US$0.31 in Mexico, whereas it costs US$6.64 in the U.S.A. Pricing conditions of rivastigmine, galantamine and memantine appear to be similar to that of donepezil. The cheapest branded originators are from India and Mexico. However, in terms of PPP, Alzheimer's drugs in other low- and middle-income countries are much more expensive than in high-income countries. Most people in low- and middle-income countries cannot afford Alzheimer's drugs. CONCLUSIONS: Alzheimer's drugs, albeit available, are often unaffordable for those who need them most. It is hoped that equitable differential pricing will be applied to Alzheimer's drugs.

Modeling the cost-effectiveness of galantamine for mild to moderately severe Alzheimer's disease in Korea.

OBJECTIVE: The aim of the study was to determine the cost-effectiveness, from the third-party payer viewpoint, of galantamine compared with usual care in the treatment of mild to moderately severe Alzheimer's disease (AD). METHODS: An existing Markov model was adapted to Korea to predict long-term outcomes over a 5-year time horizon and to estimate the cost-effectiveness of galantamine for the treatment of AD. The model structure is informed by a review of national and international literature on the clinical and cost-effectiveness of galantamine and on the costs and outcomes associated with treatment for AD. The main outcome measure used was the cost per quality-adjusted life year (QALY) gained. All costs were indexed to US$ (2007 value). Multivariate probabilistic sensitivity analysis and scenario analysis were undertaken to assess uncertainty in the results. RESULTS: The study findings indicate that the clinical benefits on AD progression from galantamine treatment resulted in an incremental cost per QALY gained of US$4939 over 5 years (vs. usual care). Probabilistic sensitivity analysis and cost-effectiveness acceptability curve suggest that the probability of galantamine treatment having an incremental cost per QALY over US$6740 is zero. Incremental cost per QALY gained according to scenario analyses ranged from US$2271 to US$8335. CONCLUSION: These findings suggest that the use of galantamine may be a cost-effective use of Korean national health-care resources, considering the gross domestic product per capita of US$21,695 in 2007.

Comparison of cholinesterase inhibitor utilization patterns and associated health care costs in Alzheimer's disease.

BACKGROUND: Sustained treatment with a cholinesterase inhibitor (ChEI) is used in the management of the symptoms of Alzheimer's disease (AD). However, the characteristic declines in learning and memory seen in AD may erode the patient's ability to adhere to medication regimens with or without caregiver support. OBJECTIVES: To examine differences by type of ChEI in (1) monthly prevalence of use, (2) nonpersistence, (3) switching from the index drug to another ChEI, (4) number of days on therapy, (5) medication possession ratio (MPR), and (6) an estimate of the relationship of these characteristics to total annual health care expenditures. METHODS: Data were from the MarketScan Medicare Supplemental and Coordination of Benefits 2001-2003 database, which comprised 1.47 million Medicare beneficiaries during this 3-year time period. Inclusion criteria were: (1) aged 65 years or older; (2) at least 1 claim with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 331.0 for AD in any of 15 diagnosis fields on outpatient claims or any of 2 diagnosis fields on inpatient claims at any time during 18 months of observation; (3) at least 1 pharmacy claim for donepezil, galantamine, or rivastigmine preceded by a 6-month period without a ChEI claim; and (4) at least 12 months of follow-up data, for a minimum 18 months continuous enrollment. Multivariate analyses, including logistic regression and exponential conditional mean models, tested for cohort differences in ChEI utilization, controlling for demographics, region of the country, type of insurer, and the Charlson Comorbidity Index (comorbid diagnoses). Using exponential conditional mean models, we also examined the relationship between utilization characteristics and all-cause (i.e., not specific to AD) health care expenditures for a 12-month period, including inpatient and outpatient (physician) care, laboratory and radiology services, emergency room (ER) use, prescription drugs, and long-term care services (e.g., nursing home care, home health visits) paid by Medicare or private insurance, but excluding long-term care services paid by Medicaid. Expenditure was defined as allowed charge (i.e., the total payment received by the service provider including plan and patient paid amounts.) RESULTS: More than 70% of the patients who received ChEI therapy and who otherwise met the inclusion criteria were excluded from this study due to the absence of at least 1 claim with a diagnosis for AD. Of the 3,177 patients included in the study, the index ChEI was donepezil for 62.8% of the patients (n=1,994); 17.2% received galantamine (n=546) and 20.1% received rivastigmine (n=637). The total number of days of index therapy dispensed was greater for those starting on donepezil (mean [median, SD] days=226 [263, 115]) compared with rivastigmine (206 [233, 120], P<0.001), but was not significantly different compared with galantamine (216 [250, 119], P=0.085). Monthly prevalence of use was similar for the 3 drugs until month 5 when a smaller proportion of rivastigmine patients had index medication on hand (65.9%) compared with 72.1% of donepezil patients (P=0.003) and 72.7% of galantamine patients (P=0.012). At 12 months, the likelihood of receiving the index ChEI was higher for donepezil (61.1%) than for either rivastigmine (50.1%, P<0.001) or galantamine (56.4%, P=0.048) and was higher for galantamine than for rivastigmine (P=0.030). The rate of switching for donepezil patients was significantly lower (14.5%) than the switch rate for rivastigmine patients (21.5%, P<0.001) and was similar to the switch rate for galantamine patients (15.0%, P=0.781 for donepezil vs. galantamine; P=0.004 for galantamine vs. rivastigmine). Rates of nonpersistence, measured as having at least 1 gap in therapy of 30 days or more during the 1-year follow-up, were 63.5% for donepezil, 63.7% for galantamine (P=0.933 for donepezil vs. galantamine), and 68.0% for rivastigmine (P=0.042 for donepezil vs. rivastigmine). MPRs and total days supply of any ChEI did not significantly differ among the 3 drugs. Results of multivariate models showed that, controlling for index ChEI drug, each additional month of ChEI treatment was associated with a reduction of 1% in total all-cause health care costs. The mean (SD) total all-cause 1-year health care costs for patients initiated on the 3 ChEIs were not significantly different: $12,112 ($16,437) for donepezil, $12,137 ($19,154) for galantamine (P=0.978), and $12,853 ($14,543) for rivastigmine (P=0.278). CONCLUSIONS: During the first year following initiation of ChEI therapy, patients initiated on donepezil had a greater days supply of the index medication than did patients initiated on rivastigmine. At 12 months following treatment initiation, the proportion of patients in therapy was higher for donepezil than for either rivastigmine or galantamine and was higher for galantamine than for rivastigmine. Patients treated with either donepezil or galantamine were less likely to switch from the index drug to another ChEI than were patients treated with rivastigmine. All-cause 1-year health care costs for patients initiated on the 3 ChEIs were not significantly different.

Economic and clinical benefits of galantamine in the treatment of mild to moderate Alzheimer's disease in a Korean population: a 52-week prospective study.

To evaluate the impact of galantamine treatment on the function, caregiver time, and resource used in the treatment of patients with mild to moderate Alzheimer's disease (AD), costs and outcomes were evaluated during a 52-week prospective, randomized, double-blind, community-controlled trial of galantamine. Patients received either galantamine treatment (n=72) or no treatment (n=66). The analysis was performed from a societal perspective. Galantamine treatment reduced time spent caring for the patients and maintained improved functional capacity, whereas, when no treatments were given, a great increase in caregiver time and progressive functional deteriorations were observed. Saved caregiver time was equivalent to 113 working days per year. After 52 weeks, mean total annual costs per patient were 14,735,000 Korea Won (KRW) (USD 12,315) for patients with galantamine treatment and 25,325,000 KRW (USD 21,166) for patients without treatment. Adjusted annual cost saving of galantamine treatment was 6,428,000 KRW (USD 5,372) when compared to no treatment (p=0.0089). Galantamine had a beneficial effect not only to slow functional decline in patients with mild to moderate AD, but also to save a substantial amount of costs, closely related to reduction in caregiver burden and decrease in caregiver time.

Economic and Clinical Benefits of Galantamine in the Treatment of Mild to Moderate Alzheimer's Disease in a Korean Population: A 52-Week Prospective Study

To evaluate the impact of galantamine treatment on the function, caregiver time, and resource used in the treatment of patients with mild to moderate Alzheimer's disease (AD), costs and outcomes were evaluated during a 52-week prospective, randomized, double-blind, community-controlled trial of galantamine. Patients received either galantamine treatment (n=72) or no treatment (n=66). The analysis was performed from a societal perspective. Galantamine treatment reduced time spent caring for the patients and maintained improved functional capacity, whereas, when no treatments were given, a great increase in caregiver time and progressive functional deteriorations were observed. Saved caregiver time was equivalent to 113 working days per year. After 52 weeks, mean total annual costs per patient were 14,735,000 Korea Won (KRW) (USD 12,315) for patients with galantamine treatment and 25,325,000 KRW (USD 21,166) for patients without treatment. Adjusted annual cost saving of galantamine treatment was 6,428,000 KRW (USD 5,372) when compared to no treatment (p=0.0089). Galantamine had a beneficial effect not only to slow functional decline in patients with mild to moderate AD, but also to save a substantial amount of costs, closely related to reduction in caregiver burden and decrease in caregiver time.

The clinical and cost-effectiveness of donepezil, rivastigmine, galantamine and memantine for Alzheimer's disease.

OBJECTIVES: To provide an update review of the best quality evidence for the clinical effectiveness and cost-effectiveness of donepezil, rivastigmine and galantamine for mild to moderately severe Alzheimer's disease (AD) and of memantine for moderately severe to severe AD. DATA SOURCES: Electronic databases, experts in the field and manufacturer submissions to the National Institute for Health and Clinical Excellence (NICE). REVIEW METHODS: A systematic review of the literature and an economic evaluation were undertaken. The quality of included randomised controlled trials (RCTs) was assessed using criteria developed by the NHS Centre for Reviews and Dissemination. An outline assessment of economic evaluations was undertaken using a standard checklist. The clinical and cost-effectiveness data were synthesised through a narrative review with full tabulation of the results of included studies. Where appropriate, meta-analysis of data was undertaken. RESULTS: For mild to moderately severe AD, the results of the study suggested that all three treatments were beneficial when assessed using cognitive outcome measures. Global outcome measures were positive for donepezil and rivastigmine, but mixed for galantamine. Results for measures of function were mixed for donepezil and rivastigmine, but positive for galantamine. Behaviour and mood measures were mixed for donepezil and galantamine, but showed no benefit for rivastigmine. For memantine, two published RCTs were included; in one of these trials the participants were already being treated with donepezil. The results suggest that memantine is beneficial when assessed using functional and global measurements. The effect of memantine on cognitive and behaviour and mood outcomes is, however, less clear. Literature on the cost-effectiveness of donepezil, rivastigmine and galantamine was dominated by industry-sponsored studies, and studies varied in methods and results. Of the three UK studies, two report donepezil as not cost-effective, whereas a third study reports an additional cost (1996 pounds sterling) of between 1200 pounds sterling and 7000 pounds sterling per year in a non-severe AD health state (concerns over these estimates are raised, suggesting that they may underestimate the true cost-effectiveness of donepezil). Cost-effectiveness analysis undertaken in this review suggests that donepezil treatment has a cost per quality-adjusted life-year (QALY) in excess of 80,000 pounds sterling, with donepezil treatment reducing the mean time spent in full-time care (delays progression of AD) by 1.42-1.59 months (over a 5-year period). From four published cost-effectiveness studies, two UK studies report additional costs associated with rivastigmine treatment. Cost-effectiveness analysis undertaken in the current review suggests that rivastigmine treatment has a cost per QALY in excess of 57,000 pounds sterling, with rivastigmine treatment reducing the mean time spent in full-time care (delays progression) by 1.43-1.63 months (over a 5-year period). From five published cost-effectiveness studies, one UK study reports a cost per QALY of 8693 pounds sterling for 16-mg galantamine treatment and 10,051 pounds sterling for 24-mg galantamine treatment (concerns raised suggest that this may underestimate the true cost-effectiveness of galantamine). Cost-effectiveness analysis undertaken in the present review suggests that galantamine treatment has a cost per QALY in excess of 68,000 pounds sterling, with galantamine reducing the time spent in full-time care (delays progression) by 1.42-1.73 months (over a 5-year period). From two published cost-effectiveness studies, one reports analysis for the UK, finding that memantine treatment results in cost savings and benefits in terms of delaying disease progression (concerns raised suggest that this may underestimate the true cost-effectiveness of memantine). In the current review, the cost-effectiveness of memantine has not been modelled separately, but where alternative parameter inputs on the cost structure and utility values have been used in a reanalysis using the industry model, the cost-effectiveness is reported at between 37,000 pounds sterling and 52,000 pounds sterling per QALY, with this alternative analysis still based on what is regarded as an optimistic or favourable effectiveness profile for memantine. CONCLUSIONS: Although results from the clinical effectiveness review suggest that these treatments may be beneficial, a number of issues need to be considered when assessing the results of the present review, such as the characteristics of the participants included in the individual trials, the outcome measures used, the length of study duration, the effects of attrition and the relationship between statistical significance and clinical significance. Many included trials were sponsored by industry. For donepezil, rivastigmine and galantamine, the cost savings associated with reducing the mean time spent in full-time care do not offset the cost of treatment sufficiently to bring estimated cost-effectiveness to levels generally considered acceptable by NHS policy makers. It is difficult to draw conclusions on the cost-effectiveness of memantine; it is suggested that further amendments to the potentially optimistic industry model (measure of effect) would offer higher cost per QALY estimates. Future research should include: information on the quality of the outcome measures used; development of quality of life instruments for patients and carers; studies assessing the effects of these interventions of durations longer than 12 months; comparisons of benefits between interventions; and research on the prediction of disease progression.

[Cost-effectiveness of galantamine in a german context]. / Kosteneffektivität von Galantamin in Deutschland.

OBJECTIVE: The application of acetylcholinesterase (AChE) inhibitors seems to be constrained in the German health care system. We investigate the cost-effectiveness of the AChE inhibitor Galantamine for patients with Alzheimer's disease (AD) in a German context. METHOD: A Markov model as the decision theoretic framework is applied to compare two treatment scenarios (Placebo vs. Galantamine). The incremental cost-utility ratio based on different sources of data is calculated as decision criteria. RESULTS: In the base case, the application of the AChE inhibitor Galantamine is a dominant scenario with cost savings along with gained quality adjusted life years. It is not cost saving from the perspective of third party payers in Germany. Results are sensitive regarding assumptions about efficacy of the drug and mortality in the analysed cohort. CONCLUSION: The German reimbursement system places an obstacle to the application of Galantamine. Further research is needed to tackle uncertainties in the model.

Assessing the health and economic impact of galantamine treatment in patients with Alzheimer's disease in the health care systems of different countries.

INTRODUCTION: Cholinesterase inhibitors have been shown to improve cognitive function and improve or maintain global function. OBJECTIVE: To estimate the long-term economic impact of treating patients with Alzheimer's disease with galantamine in seven healthcare systems: Australia, Canada, Finland, New Zealand, Sweden, the Netherlands and the UK. METHODS: The time until patients require full-time care (FTC), defined as the consistent requirement for a significant amount of care giving and supervision each day, and the associated costs were evaluated using the 'Assessment of Health Economics in Alzheimer's Disease (AHEAD)' model. Efficacy data were obtained from three clinical trials comparing galantamine with placebo and local cost and resource use data were determined for each country. Forecast costs reported in Euros (2001 value), were made for up to 10 years in each healthcare system. All costs were determined from a perspective somewhat broader than that of a comprehensive payer, including social services. Both benefits and costs were discounted at 3%. RESULTS: Galantamine (16 mg/day) is predicted to delay the need for FTC by 6.8%, thus the cumulative cost of care over 10 years is expected to be reduced, and this offsets much or all of the cost of galantamine. Approximately five patients need to be treated to avoid 1 year of FTC. In each healthcare system, FTC was estimated to account for 61-92% of the cost. Savings were estimated for most of the countries. For those countries with an expected expense, there were reasonable costs per FTC month avoided (euro553, discounted) and costs per quality-adjusted life year gained (euro25,000). CONCLUSION: In addition to the clinical benefits associated with galantamine treatment, the savings predicted from delaying FTC may offset the treatment costs.

Assessment of health economics in Alzheimer's disease (AHEAD): treatment with galantamine in the UK.

OBJECTIVE: To assess the long-term health and economic impact of treating mild to moderate Alzheimer's disease (AD) with galantamine (16 mg or 24 mg per day) compared to no cholinesterase therapy in the UK. METHODS: The long-term costs and outcomes were assessed using a model developed from longitudinal data on a cohort of AD patients. The model predicts the time until patients require full-time care, defined as the consistent requirement for a significant amount of care and supervision each day. Efficacy data were obtained from three clinical trials comparing galantamine with placebo, forecasts were made for ten years. Costs were determined in 2001 British pounds and discounted at 6% per annum, while outcomes such as time to full-time care were discounted at 1.5%. RESULTS: Without pharmacological treatment, patients are expected to incur costs of 28,134 British pounds over ten years, 70% of costs accrue from providing full-time care. Galantamine (16 mg per day) is predicted to reduce the duration of the full-time care state by 12%; approximately five patients need to be treated to avoid one year of full-time care. The ten-year incremental costs per month of full-time care avoided average pound 192 British pounds per patient and 8,693 British pounds per QALY. Savings (1380 British pounds) are predicted for patients who continue treatment beyond six months and whose cognitive function is maintained or improved. Comparable results were estimated for the 24 mg dose. CONCLUSION: In addition to the clinical benefits associated with galantamine treatment, the savings predicted from delaying when full-time care is needed may offset the treatment costs.

Economic evaluation of galantamine in the treatment of mild to moderate Alzheimer's disease in the United States.

BACKGROUND: Alzheimer's disease (AD) is estimated to affect up to 11% of those aged > or =65 years in the United States, and the number of patients with AD is predicted to increase over the next few decades as the population ages. The substantial social and economic burden associated with AD is well established, with the cost of management increasing as the disease progresses. OBJECTIVE: The aim of this study was to evaluate the economic impact of galantamine 16 and 24 mg/d relative to no pharmacologic treatment in the management of mild to moderate AD in the United States based on the concept of need for full-time care (FTC). METHODS: Calculations were made using the Assessment of Health Economics in Alzheimer's Disease model, which applies predictive equations to estimate the need for FTC and the associated costs. The predictive equations were developed from longitudinal data on patients with AD. Inputs to the equations were derived by analyzing the data from 2 randomized, placebo-controlled, galantamine clinical trials. Resource use (from a payer perspective) was estimated from US clinical trial data, and costs were estimated from several US databases. Analyses were carried out over 10 years, and costs and benefits were discounted at 3%. RESULTS: In the base case, 3.9 to 4.6 patients need to start treatment with galantamine to avoid 1 year of FTC, depending on dose. Treated patients spent 7% to 8% more time pre-FTC and 12% to 14% less time requiring FTC, resulting in savings of 2408 to 3601 US dollars. Time horizons below 3 years, very high discontinuation rates, or increased survival with galantamine reversed the savings. Conversely, limiting treatment to responders delayed FTC by 6 to 7 months, with savings of approximately 9097 to 11,578 US dollars. CONCLUSIONS: These results suggest that use of galantamine in patients with AD in the United States could reduce the use of costly resources such as formal home care and nursing homes, leading to cost savings over time.

Galantamine hydrobromide: an agent for Alzheimer's disease.

The pharmacology, dosage, adverse effects, efficacy, and economics of galantamine hydrobromide are discussed. Galantamine hydrobromide is a tertiary alkaloid that has been extracted from plant sources and is now synthesized for use in the treatment of mild to moderate Alzheimer's disease (AD). Galantamine acts both as a reversible competitive inhibitor of acetylcholinesterase (AChE) and as an allosteric modulator of nicotinic acetylcholine receptors. The recommended starting dosage is 4 mg (as the hydrobromide) twice daily. The dosage should be increased in increments of 8 mg/day in two divided doses after four weeks at a given dosage until a maintenance dosage of 16-24 mg/day in two divided doses is reached. Adverse effects are primarily mild and cholinergic and include nausea, vomiting, diarrhea, and dizziness. Five large clinical trials demonstrated that galantamine is more effective than placebo in controlling the symptoms of mild to moderate AD. Optimal therapy appears to require early initiation of the drug and a dosage-adjustment period of eight weeks. In one study, galantamine delayed full-time care by 10% and reduced the overall cost of care by $528. Because galantamine has not yet been compared directly with other AChE inhibitors, cost should be the principal factor weighed during formulary evaluations. Galantamine provides the clinician with another choice of an AChE inhibitor for use in treating AD.