Today I want to once again report from the 51st Congress of the American College of Neuropsychopharmacology (ACNP), 2nd – 6th December 2012 in Hollywood, Florida, even though the Congress has already ended. The study was presented as a poster, but I believe it could have been also presented in the “Highlights” session, in which unfortunately the preclinical work dominated (see my last posting dated 12/04/2012).
At least in Germany, acetylcholinesterase inhibitors still have the reputation of being of dubious benefit in patients with dementia of the Alzheimer’s type. It is widely believed that their effect is limited and is in no way proportionate to the adverse effects and costs.
Klaus Hager from the Center for Medicine in Old Age in the Diakonie Hospital Henriettenstiftung in Hannover, Germany, now reported on the results of a large multicenter double-blind placebo-controlled study in patients with mild to moderate Alzheimer’s dementia, who were treated with Galantamin or Placebo. While the regulatory studies usually had a treatment duration of six months, the extraordinary characteristic of this new study is its duration of two years (!). The size of the study is also remarkable. There were 2225 patients screened and 2051 were randomized. More than 1000 patients in each group received the study drug. The Mini Mental State Examination (MMSE) score was 19.0 points at baseline in both groups. The mean age was 73 years in both groups, about two-thirds of the patients were female. The patients were treated with 16-24 mg galantamine daily. The primary efficacy endpoint was the change in MMSE score from baseline until month 24, a secondary efficacy endpoint was the change in the daily activities – as measured by the Disability Assessment in Dementia (DAD) scale – from baseline to the months 12 and 24. The primary safety endpoint was mortality.
After all, 339 patients treated with galantamine and 322 of the placebo-treated patients completed the study after two years. About two-thirds of the patients had been treated with the maximum dose of 24 mg galantamine, only 3.4% received less than the targeted 16 mg. In the group of patients treated with galantamine, the MMSE score decreased by 1.4 points (LOCF analysis) after two years, in the group of patients treated with placebo by 2.1 points. This difference was statistically highly significant (p <0.001). Also with regard to the change in the DAD score, galantamine was significantly superior to placebo (after two years: placebo 10.8 points decrease, galantamine 8.2 points, p = 0.002). New in this study, however, was the result of the analysis of safety data: In the placebo group 56 deaths occurred (5.5%), in the galantamine group, 33 (3.2%). This difference was statistically significant (p = 0.011). Thus, the mortality was reduced to almost half (hazard ratio 0.58, 95% CI 0.37 to 0.89). The rate of adverse events in patients treated with galantamine was only slightly higher than in the placebo group (54.0% vs. 48.6%). Serious adverse reactions were similarly frequent in both groups.
This is the first study with an acetylcholinesterase inhibitor, which not only shows once again that the reduction of cognitive performance and activities of daily living can be slowed by these substances, but also for the first time provides evidence that the treatment can reduce the mortality of the disease. Whether the results can be generalized to other acetylcholinesterase inhibitors is unclear.
This post is also available in: German