Rivastigmine

Alzheimer’s disease is associated with a large cost burden, of which institutionalised care constitutes a major component. Therefore, the decision to move a patient from the community to institutionalised care is associated with a significant increase in direct costs. About three-quarters of patients with Alzheimer’s disease are admitted to a nursing home within 5 years of diagnosis. Unpaid or informal caregiver time is another large cost in Alzheimer’s disease, especially for patients cared for in the community; informal care can account for up to three-quarters of healthcare costs in non-institutionalised patients.

Several cholinesterase inhibitors, of which rivastigmine is one, are available for the treatment of patients with mild to moderate Alzheimer’s disease. By improving cognitive function and slowing the rate of cognitive decline, cholinesterase inhibitor therapy may reduce a significant part of the economic burden of the disease by delaying the move to institutionalised care. In the absence of prospective long term data which focus on pharmacoeconomic end-points, modelling techniques have been used to extrapolate clinical data available for some cholinesterase inhibitors, including rivastigmine.

Four economic analyses, based on a single model of cognitive decline, have been performed with rivastigmine from the perspective of the provider or society. All show that rivastigmine therapy (excluding drug-related costs) is associated with cost savings in patients with mild to moderate Alzheimer’s disease by delaying the time to institutionalisation. If the acquisition cost of the drug was factored in, the cost savings completely or partially offset treatment costs. The magnitude of the cost savings increased as the time horizon increased (up to 2 years). The largest savings were realised in patients with mild disease over a 2-year time-frame, suggesting that treatment should be initiated early from an economic viewpoint. Pharmacoeonomic data comparing different cholinesterase inhibitors are, as yet, unavailable.

Alzheimer’s disease is characterised by progressive loss of memory and cognitive function. It is the most common form of dementia with an average prevalence of about 5% (range 3.4 to 6.7%) in those aged 65 years or over. Between the ages of 65 and 90 years, the incidence of Alzheimer’s disease doubles for approximately every 5 years of age gained.

In addition to symptoms of cognitive decline and short term memory loss, some patients also experience psychiatric and behavioural disturbances as the disease progresses. The ability to perform basic activities of daily living, such as dressing, bathing and eating, also decreases once the disease becomes moderately severe. Severe dementia is characterised by complete dependence on caregivers.

Patients with Alzheimer’s disease are often cared for at home. Caregivers carry a considerable burden of emotional and physical strain. They are required to perform numerous tasks which can vary from assistance with high level tasks (such as managing finances) in the early stages of the disease to basic tasks (such as bathing) when the disease becomes more severe. There is a direct association between carer burden and behavioural symptoms. As the disease progresses and more supervision is required, the patient may be moved to institutionalised care. About three-quarters of patients with Alzheimer’s disease are admitted to a nursing home within 5 years of diagnosis and typically require care for up to 8 years.

Alzheimer’s disease is associated with a considerable cost burden. Estimates of the cost of care for a patient with Alzheimer’s disease range from approximately US dollars ($US) 17 000 to $US55 000 per annum (1995 values). Costs increase with increasing disease severity; the respective estimated annual costs for patients with mild, moderate and severe disease are $US18 408, $US30 096 and $US36 132 (1996 values).

Institutionalised care is the largest single component of healthcare costs in patients with more severe Alzheimer’s disease. Therefore, the decision to move a patient from the community to institutionalised care is associated with a significant increase in direct costs. Unpaid caregiver time (or informal care) also makes up a large proportion of costs, especially in patients with milder disease cared for at home. In non-institutionalised patients, unpaid care accounted for 50 to 74% of total costs for patients with Alzheimer’s disease.

Symptomatic treatment for patients with Alzheimer’s disease is currently focused on augmentation of cholinergic neurotransmission. Several cholinesterase inhibitors are now available and all achieve a similar level of improvement in cognitive function. Differences between agents therefore relate not to their effects on cognition, but rather to differences in effects on behavioural symptoms and their tolerability, pharmacological and potential drug interaction profiles.

Rivastigmine, like other cholinesterase inhibitors, produces modest improvements in cognitive function. Two pivotal trials showed that rivastigmine, at an oral dosage of 6 to 12 mg/day, significantly improved measures of cognitive function after 26 weeks of treatment versus placebo in patients with mild to moderate Alzheimer’s disease. Caregiver-rated activities of daily living also improved in significantly more patients receiving rivastigmine in both trials (25 and 29% vs 15 and 19% with placebo). Rivastigmine also was superior to placebo on the Clinician’s Interview Based Impression of Change Plus (CIBIC-plus)] scale, which measures global functioning. In addition, noncomparative clinical trials show that rivastigmine offers long term benefits on behavioural symptoms in patients with Alzheimer’s disease.

As with other cholinesterase inhibitors, the adverse events most commonly associated with rivastigmine are cholinergic in nature. These include nausea, vomiting, diarrhoea and anorexia, and were reported in 14 to 50% of patients receiving rivastigmine 6 to 12 mg/day compared with 2 to 11% of placebo recipients in clinical trials.Most events are of mild to moderate intensity, dose-related and of limited duration. About one-quarter of patients receiving rivastigmine 6 to 12 mg/day discontinue treatment because of adverse events. No clinically relevant changes in laboratory or vital signs (including hepatic enzymes) are observed.

In producing modest improvements and, more importantly, slowing the decline of cognitive function, cholinesterase inhibitors may have the potential to decrease a significant part of the economic burden of Alzheimer’s disease by delaying the time to institutionalisation. Long term prospective data are required to quantify and assess the costs of these effects but are currently unavailable. In the interim, an alternative option is to use modelling techniques on pivotal clinical trial data to estimate the long term cost implications of treatment. Such an approach has been used with rivastigmine and some other cholinesterase inhibitors.

A model based on pivotal clinical trial data in patients with mild to moderate Alzheimer’s disease has been developed to estimate the delay in cognitive decline offered by rivastigmine over placebo. This model forms the basis for 4 pharmacoeconomic analyses on rivastigmine.Mini-Mental State Examination scores are used as a measure of disease progression or cognitive decline, and an accelerated life model is used to extrapolate the data beyond the end of the clinical trials (1 and 2 years). Each analysis assessed slightly different components of cost, although all costs were derived from recent cost-of-illness data from the US, UK or Canada.

The analyses show that treatment with rivastigmine 6 to 12 mg/day is associated with cost savings (exclusive of drug-related costs) in patients with mild to moderate Alzheimer’s disease. The magnitude of the savings increased as the time horizon increased. For example, in the most recent US analysis, savings achieved per patient with mild disease were $US83, $US683 and $US4768 after 6 months, 1 and 2 years, respectively.

When disease severity was considered, the greatest savings were realised in those with mild disease over a 2-year time-frame. However, over a time-frame of less than 2 years, greater costs savings were observed in those with moderate disease because institutionalisation is more likely in this patient group.