NEW ORLEANS—After receiving a 13.3-mg/24-hour rivastigmine transdermal patch for 48 weeks, patients with mild to moderate Alzheimer’s disease showed significantly less decline in the capacity to perform daily living activities than did patients receiving the 9.5-mg/24-hour patch at 48 weeks, according to data from a phase III trial reported at the 64th Annual Meeting of the American Academy of Neurology.
“The safety profile of the 13.3-mg/24-hour patch was consistent with that seen for the 9.5-mg/24-hour patch in this study and in previous reports,” said lead author Jeffrey Cummings, MD, ScD, Director of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas, and colleagues. “The study did not show any unexpected side effects of long-term treatment with either [patch dose].”
The OPTIMA Study
Dr. Cummings’s group conducted the multicenter Optimizing Transdermal Exelon in Mild-to-moderate Alzheimer’s disease (OPTIMA) study, a 72- to 96-week trial with a 24- to 48-week initial open-label phase using a 9.5-mg/24-hour patch. The initial open-label phase included 1,584 persons ages 50 to 85 with a diagnosis of Alzheimer’s disease, a clinical diagnosis of probable Alzheimer’s disease, and a Mini-Mental State Examination score between 10 and 24.
After the open-label phase, 567 (35.8%) patients who met functional decline criteria and cognitive decline criteria were randomized in the 48-week, double-blind, double-dummy, parallel group phase to a 9.5-mg/24-hour rivastigmine transdermal patch group (287 patients) or a 13.3-mg/24-hour group (280 patients). All treatment groups had similar baseline demographics and mean duration of drug exposure.
Outcomes After Randomization
The researchers set primary efficacy outcomes of change from double-blind randomization baseline to week 48 on the Alzheimer’s Disease Cooperative Study–Instrumental Activities of Daily Living Scale (ADCS-IADL) and the Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-cog).
Results showed that patients in the 13.3-mg/24-hour patch group declined less on the ADCS-IADL than did patients in the 9.5-mg/24-hour patch group at all time points, with a statistically significant difference noted from week 16 onward. In addition, patients in the 13.3-mg/24-hour patch group declined less on the ADAS-cog at 24 weeks but not at 48 weeks, compared with patients in the 9.5-mg/24-hour patch group.
Secondary Outcomes
Secondary efficacy outcomes were also established, including time to functional decline, which was defined as at least a one-point decrease in the ADCS-IADL score in a visit, confirmed by the next visit, or at least a two point-decrease in the ADCS-IADL from double-blind baseline and at least one point less at the following visit.
The investigators found that patients in the 13.3-mg/24-hour patch group experienced longer time to functional decline than did patients in the 9.5-mg/24-hour patch group. However, the difference in time to functional decline was not statistically significant between the groups.
Other secondary efficacy outcomes results—the change from double-blind baseline to week 48 on the Trail Making Test (Parts A and B) and the 10-item Neuropsychiatry Index—showed no statistical significance between the groups.
Investigating Safety
According to reports of safety outcomes, the 13.3-mg/24-hour patch group had more adverse events (75.0%) than the 9.5-mg/24-hour patch group (68.2%), though the higher prevalence of adverse events in the 13.3-mg/24-hour group only occurred in the first 24 weeks. Adverse event rates for both groups were similar in the second 24 weeks.
Furthermore, both groups experienced similar incidences of general disorders (13.3 mg/24 h, 23.2%; 9.5 mg/24 h, 21.2%), including gastrointestinal problems (29.3% versus 19.1%), as well as psychiatric (25.4% versus 21.6%) and nervous system (21.4% versus 18.4%) disorders.
The study authors noted that although the incidence of adverse events appeared to be dose-related, “the total incidence of adverse events in weeks 25 to 48 was comparable between treatment groups, suggesting that the greater incidence of adverse events in the 13.3-mg/24-hour patch group during the double-blind phase was likely associated with titration to the higher dose.”
Fewer patients discontinued use of the 13.3-mg/24-hour patch (9.6%) due to adverse events, compared with the 9.5-mg/24-hour patch (12.7%).
“Functional decline is one of the most challenging aspects of Alzheimer’s disease for patients and caregivers,” said Dr. Cummings. “If it becomes available, the 13.3-mg/24-hour patch would provide another option in the repertoire of treatments available to practitioners managing patients who are declining despite treatment.”
—Lauren LeBano