Patients with advanced Alzheimer's disease treated with 13.3 mg rivastigmine patch showed greater improvements in cognitive, functional, and behavioral performance from baseline compared to patients who received 4.6 mg patches.
Martin Farlow, MD, shared findings on the efficacy of the 13.3 mg/24hr rivastigmine patch for the treatment of severe Alzheimer’s Disease. The findings were presented as part of a poster session at the 2013 Annual Meeting of the American Neurological Association. Dr. Farlow is a Professor of Neurology at the Indiana University School of Medicine in Indianapolis.
The ACTION study was a 24-week randomized study that focused on the activities of daily living and cognition in patients with severe Alzheimer’s disease. The study evaluated the efficacy, safety, and tolerability of rivastigmine, an acetylcholinesterase inhibitor. In this study, patients given 13.3 mg rivastigmine patches showed significantly less deterioration than patients given 4.6 mg patches (as measured by the Severe Impairment Battery and the AD Cooperative Study—Activities of Daily Living scale—Severe Impairment Version).
The rivastigmine transdermal patch was previously approved in the US for mild to moderate Alzheimer’s disease (AD). Based on the ACTION study data, the higher dose 13.3 mg patch was also recently approved for severe Alzheimer’s disease in the US. The authors of this present study sought to analyze more data from the ACTION study to investigate the impact of this patch using secondary measures of global functioning and behavior.
All patients in this study had probable Alzheimer’s disease. Mini Mental State Examination scores ranged between three and 12. Baseline characteristics were comparable between the treatment groups.
The patients were randomized to one of two groups. 356 patients received the 13.3 mg/24 hr rivastigmine patch; 360 patients received the 4.6 mg patch. The researchers used the Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change scale (ADCS-CGIC) and the Neuropsychiatric Inventory Test (NPI-12) to assess function at baseline as well as at 8, 16, and 24 weeks of treatment.
Sixty-five percent of patients in the 4.6 mg group completed the study, with 14% withdrawing due to adverse events. Sixty-four percent of patients in the larger dose group completed the study, with 20% withdrawing due to adverse events.
On analysis, the two groups demonstrated significant differences on the ADCS-CGIC. More patients in the 13.3 mg group showed improvements in their clinical status (p=0.0094). At week 24, 24.6% of patients at the larger dose displayed an improvement in ADCS-CGIC, versus 16.2% in the smaller dose group (p=0.0094). The NPI-12 did not demonstrate significant differences between the two groups, though there was a slight trend of improvement in the larger dose group.
The two groups showed similar rates of adverse events (74.6% in the 13.3mg group versus 73.3% in the 4.6mg group). “The thing that was kind of surprising here is when you have a higher dose of a drug like this you expect to see more side effects, and in this case the percentage of people with side effects were essentially the same,” said Farlow. Some adverse effects (like agitation) were actually slightly decreased at the higher dose.
“The global ADCS was highly significant and did show benefit that you can see for the 13.3 mg dose,” said Farlow. More details of the study are available online.