Apr 2, 2012
Galantamine and rivastigmine patches: positive influence on cognition possible
But for both the drugs used to treat Alzheimer’s disease, there is also proof of harm
In a final report published on 2nd April 2012, the German Institute for Quality and Efficiency in Health Care (IQWiG) investigated whether treatment with galantamine or rivastigmine transdermal patches offers advantages to patients with Alzheimer's disease. According to this report, there is proof for galantamine - but only indications for rivastigmine patches - that the drugs can slight delay the loss of cognitive functions. However, the same studies also provide proof of possible harm, most notably in the form of more frequently occurring nausea and vomiting, as well as skin irritation in the case of rivastigmine patches. There is currently no data on important other aspects of treatment such as the quality of life of patients or the need for full inpatient care.
Analysis supplements the 2007 benefit assessment of cholinesterase inhibitors
Back in 2007, IQWiG presented a benefit assessment of the drugs donezepil, galantamine and rivastigmine, which belong to the group of cholinesterase inhibitors. An updated literature search in 2009 showed that in the meantime further study data, some of which were unpublished, had become available on galantamine. In addition, rivastigmine was no longer only marketed as a tablet, but since 2007 also as a patch. Since this fact could also affect the conclusions of the first benefit assessment of 2007, the Federal Joint Committee (G-BA) commissioned IQWiG to re-investigate the benefits of galantamine and to assess rivastigmine patches for the first time.
No proof of benefit for galantamine in daily living skills
As regards the abilities to cope with the activities of daily living and accompanying psychopathological symptoms such as agitation or depression, IQWiG indeed showed differences between the treatment groups, but could not evaluate these as proof or indication of a benefit. This was because these differences were so small that is it doubtful whether those affected or their relatives could actually see them as an advantage.
But as the assessment shows, when the more recent studies are also included, there is proof that galantamine, at least in a higher dose, can have positive effects on cognition and memory in patients with mild to moderate Alzheimer's disease.
More frequent study discontinuations with galantamine
The studies also provided proof of harm: patients who took galantamine suffered from nausea or vomiting more often than those who received a placebo. In addition, patients given galantamine discontinued the study more frequently because of side effects.
These results applied to a treatment period of up to 6 months.
So far, there has been only a single long-term study on galantamine. It investigated whether it is worth extending galantamine therapy beyond 12 months in patients who had been treated for this length of time with galantamine and who responded to this treatment. This study provided a hint that the continued treatment can have a benefit in terms of cognition and memory.
Indication of benefit of rivastigmine patches only in relatively young patients
Rivastigmine patches were approved in Germany in 2007 and are available in two dosage strengths (5 cm2 und 10 cm2). In contrast to tablets, the patch does not have to be used twice, but only once daily.
In the studies IQWiG found no proof of benefit of the new dosage form - either for the cognitive or for the practical daily living skills. Compared to a placebo patch, only the higher dose (10 cm2) showed differences in respect of cognition. For patients under 75 years of age, IQWiG assesses this as an indication, for the over 75 year-olds, a hint of a benefit. The main reason that IQWiG sees no proof of benefit here is that the results observed in the studies are not sufficiently robust.
Skin irritation more frequent with rivastigmine patches
But rivastigmine patches also have a risk of harm: with the lower dosage used in the studies IQWiG found indications of harm - and with the higher dosage, proof. In addition to nausea and vomiting, occurring more often with the 10 cm2 patch, both dosages triggered increased skin irritation.
It is not clear from the only study which directly compared both application forms of rivastigmine, that the patch is inferior to the tablet. However this study was not designed to also demonstrate this inferiority. This important question therefore remains unanswered. "As an argument in favour of the patch, it is often said that gastrointestinal side effects are less common. However our assessment shows that instead other side effects, namely skin problems, occur more frequently. And these can be quite burdensome. In addition, the data on the improvement in cognition and memory are not as clear as with the orally-administered cholinesterase inhibitors,” explained Thomas Kaiser, Head of the Drug Assessment Department at IQWiG. "It is possible that fewer gastrointestinal problems occur only because the effect of the patch is also smaller. But we don't know that. Further studies would be necessary to find this out,” according to Thomas Kaiser.
All these results on rivastigmine apply only for a treatment period of 24 weeks, because so far there are no long-term studies.
Procedure of report production
IQWiG published the preliminary results, the "preliminary report” for discussion in July 2011. After the commenting procedure had ended, the preliminary report was revised and sent to the contracting agency (G-BA) as a final report in February 2012. The written comments will be published in a separate document at the same time as the final report. The report was prepared in collaboration with external experts.
An overview of the background, methods and further results of the final report is provided in the following executive summary.
Contact: Tel. +49(0)221-35685-0, presse@iqwig.de