Long-Term Effects of Second-Generation Cholinesterase Inhibitors on Clinical Outcomes and Costs of Alzheimer's Disease

摘要

Alzheimer's disease, which is a common disorder among the elderly, not only has devastating healthconsequences, but also poses a substantial economic burden. Three second-generation cholinesterase inhibitors -donepezil, galantamine and rivastigmine - represent the best available treatment for patients with mild-to-moderate stages of the disease. While these drugs have been effective in short-term clinical trials, it is necessary to understand the outcomes over the longer term in order to assess the appropriateness of these treatments.Data on the effectiveness of these drugs from information beyond the short-term clinical trials (e.g. long-term clinical trials and non-trial data) are now emerging. In most cases, the results indicate that, at least for some patients, continued treatment with cholinesterase inhibitors is effective in slowing cognitive decline. Whether these results translate to clinically and economically relevant outcomes is less clear. The AD2000 trial in particular, a 1-year, placebo-controlled trial, seems to suggest that cognitive benefits, even if maintained over the mid-to-long term, may not adequately reflect overall deterioration in patients. Naturalistic studies, as well as analyses of administrative data, however, mostly suggest that these benefits are real and relevant.The cost effectiveness of treatment has been evaluated primarily through modeling. These studies have shown that the costs of treatment can be offset by savings in other areas as a result of slowed disease progression. When all medical costs are considered, relatively small delays in disease progression are required to offset treatment costs, but a large portion of these offsetting savings are a result of delayed institutionalization. To payers not responsible for institutional care costs, these predicted economic advantages are less relevant. While data are limited, some research indicates that reductions in other costs may be sufficiently large to fully offset the costs of treatment,Economic comparisons among active treatments have only been made in one study so far. Based on meta-analyses of trial data and a model estimating disease progression, that study concluded that galantamine provided the best health and economic projections. Head-to-head studies, however, are limited and provide conflicting results.While the treatment of patients with Alzheimer' s disease using cholinesterase inhibitors will likely continue to increase, there is no definitive answer regarding the appropriateness of long-term treatment. A reasonably complete answer will likely not be available until more long-term data from actual practice become available.