LONDON (Reuters) - Pfizer's dementia drug Aricept, already commonly used to treat mild to moderate Alzheimer's disease, can also help patients with severe disease and should be used more widely and for longer, according to research published on Wednesday.
British scientists who studied the possible longer-term benefits of giving Aricept suggested that extending treatment could help twice as many Alzheimer's sufferers worldwide.
The study also looked at another commonly used dementia drug called memantine, which is sold in the United States under the brand Namenda by Forest Laboratories and Germany's Merz, and in Britain under the brand Ebixa by Danish group Lundbeck.
It found that keeping patients with moderate to severe Alzheimer's on Aricept, or donepezil as it is known generically, or starting them on memantine treatment, meant they had significantly better cognitive and function abilities than patients taking a placebo or dummy pill.
An estimated 18 million people worldwide suffer from Alzheimer's disease, which is the most common form of dementia. It is fatal brain disease that affects memory, thinking, behaviour and the ability to handle daily activities and is placing an increasingly heavy burden on societies and economies across the world.
According to the World Health Organisation, some 35 million people worldwide have dementia, and Alzheimer's Disease International predicts that as populations age, dementia cases will almost double every 20 years to around 66 million in 2030 and 115 million in 2050.
The study, published in the New England Journal of Medicine, involved 295 Alzheimer's patients in Britain who were assigned to one of four separate groups - one continuing to take donepezil, one stopping donepezil and getting a placebo, one stopping donepezil and starting memantine, and a fourth taking both drugs together.
Robert Howard, a professor at King's College London who led the trial, said it was the first to show the value of continued drug treatment for patients with moderate to severe Alzheimer's.
While donepezil is commonly prescribed for patients in the early stages of the disease, doctors in some countries, including Britain, are advised to stop prescribing the drug to patients once their disease has progressed to become more severe.
"As patients progress to more severe forms of Alzheimer's disease, clinicians are faced with a difficult decision as to whether to continue or not with dementia drugs and, until now, there has been little evidence to guide that decision," Howard told reporters at a briefing abut his findings.
"(But now) we have robust and compelling evidence that treatment with these drugs can continue to help patients at the later, more severe stages."
The researchers found that patients taking Aricept were better able to remember, understand, communicate and perform daily tasks for at least a year longer than those who stopped taking it. The improvements were noticeable to patients, and their careers and doctors, Howard said.
While the effects were slightly smaller, the study also found that patients who started memantine treatment also had significantly better cognitive functional abilities that those on a placebo.
(Reporting by Kate Kelland; Editing by Andrew Callus)
Donepezil Beneficial in Moderate to Severe Alzheimer's
March 7, 2012 — The cholinesterase inhibitor donepezil (Aricept,
Pfizer), which is widely used to treat mild to moderate Alzheimer's disease
(AD), also appears to be beneficial in patients with moderate to severe
disease, new research shows.
Further, the N-methyl-d-aspartate-receptor antagonist
memantine was also shown to be beneficial in this patient population,
although its effect was more modest compared with donepezil.
The multicenter, double-blind, randomized controlled trial
conducted by investigators at King's College London in the United Kingdom is
the first study to demonstrate the value of continued drug intervention for
those patients with moderate to severe AD who have deteriorated beyond the
point where donepezil is currently recommended.
"For the first time, we have robust and compelling
evidence that treatment with these drugs can continue to help patients at the
later, more severe stages of the disease," lead author Robert Howard,
MD, from the Institute of Psychiatry at King's College, said in a statement.
The study is published
in the March 8 issue of the New England Journal of Medicine.
Limited Evidence, Difficult Decision
Most guidelines advocate treatment with a cholinesterase
inhibitor. However, the investigators note that some recommend discontinuation
of these agents when AD becomes severe.
In addition, memantine has been shown to be effective
primarily in moderate or severe AD, and 1 study suggested that combination
treatment with memantine and a cholinesterase inhibitor was more effective than
treatment with a cholinesterase inhibitor alone. However, to date, this finding
has not been replicated.
The researchers also point out that all trials examining
cholinesterase inhibitors in severe AD have been conducted in patients residing
in nursing homes. Further, none of these trials have investigated the strategy
of continuing treatment with cholinesterase inhibitors in patients already
taking these drugs.
"There is very limited evidence to guide the difficult
decision regarding the continuation or discontinuation of treatment when the
disease progresses, but continued treatment is associated with an increase in
adverse outcomes, including syncope, the need for insertion of permanent
pacemakers, and hip fractures," the investigators write.
The aim of the Donepezil and Memantine in Moderate to Severe
Alzheimer's Disease (DOMINO) trial was to determine whether continuation with
donepezil vs discontinuation of the drug would be associated with better
cognition and function over a period of 52 weeks.
The investigators also tested whether treatment with
memantine vs placebo would be associated with better cognition and function.
Finally, they examined whether combination treatment with donepezil and
memantine would have additive or synergistic benefits.
Noticeable Clinical Improvement
The study included 295 patients living in the community who
had moderate to severe AD, defined as
a score of 5 to 13 on the Standardized Mini-Mental State Examination (SMMSE),
who had been treated with donepezil for at least 3 months before trial entry.
Participants were randomly assigned to continue donepezil (n
= 73), discontinue donepezil (n = 73), discontinue donepezil and start
memantine (n=76), or continue donepezil and start memantine (n = 73) for a
period of 52 weeks.
The study's co-primary endpoints were scores on the SSMSE
and on the Bristol Activities of Daily Living Scale (BADLS). Scores on the SSMSE range from 0 to 30,
with higher scores indicating better cognitive function. In contrast, higher scores on the BADLS,
which range from 0 to 60, indicate greater impairment.
For the purposes of the study, the minimum clinically
important change in SSMSE and BADLS scores were 1.4 points and 3.5 points,
respectively.
The results showed that patients who continued donepezil had
a score on the SMMSE that was higher by an average of 1.9 points vs those who
discontinued the drug (95% confidence interval [CI], 1.3 - 2.5; P <
.001) and a score on the BADLS that was lower by 3.0 points (95% CI, 1.8 - 4.3;
P < .001).
Those assigned to receive memantine had a score on the SMMSE
that was an average of 1.2 points higher (95% CI, 0.6 - 1.8; P <
.001) and a score on the BADLS that was 1.5 points lower (95% CI, 0.3 - 2.8; P
< .02) vs participants who received placebo.
The authors note that there was no significant benefit
associated with the combination of donepezil and memantine over donepezil alone.
"We observed that patients who continued taking
donepezil were better able to remember, understand, communicate, and perform
daily tasks for at least a year longer than those who stopped taking the drugs.
These improvements were noticeable to patients, their caregivers, and
doctors," said Dr. Howard.
"As patients progress to more severe forms of
Alzheimer's disease, clinicians are faced with a difficult decision as to
whether to continue or not with dementia drugs, and until now, there has been
little evidence to guide that decision," he added.
It is estimated that 18 million people worldwide suffer
from AD, which is the most common cause of dementia. According to the World
Health Organization, of the 35 million people currently living with dementia
globally, 58% live in low- and middle-income countries, and this figure is
projected to reach 71% of the total by 2050.
"Both donepezil and memantine will soon be off
patent and available in very cheap generic preparations. These findings
will greatly increase the numbers of patients in the developed and developing
world," said Dr. Howard.
More Research Needed
In an accompanying editorial, Lon S. Schneider, MD, from the
departments of psychiatry and neurology at the University of Southern
California, notes that the fact that the average SMMSE was "1.9 points
lower...in the group that discontinued donepezil than in the group that continued
the drug is potentially important because many of the patients were severely
impaired, on the cusp of needing nursing home care, and slightly worse
cognitive function could affect their ability to remain at home."
However, Dr. Schneider cautions that the "results of
the DOMINO trial should not be interpreted as evidence of the efficacy of
indefinite treatment with the drug."
"More research is needed to assess the long-term
benefits, the potential for harm and physiological tolerance, and the safe discontinuation
of cholinesterase inhibitors as Alzheimer's disease progresses," Dr.
Schneider writes.
Further, he notes, the results with donepezil in this study
cannot necessarily be applied to other cholinesterase inhibitors, including
galantamine and rivastigmine, because the pharmacokinetics, mechanisms, and
other actions of these drugs may differ.
Disclosures for the authors and Dr. Schneider are available
at www.nejm.org.
NEJM. 2012;
366:893-903; 957-959. Abstract
沒有留言:
張貼留言