Efficacy, safety and tolerability of rivastigmine patch 13.3 mg/24h (15 cm2) versus 4.6 mg/24h (5 cm2) in patients with severe alzheimer's disease: Results of the activities of daily living and cognition (action) study

OBJECTIVE:

Investigate benefit/risk of 13.3 mg/24h rivastigmine patch in patients with severe Alzheimer's disease (AD).

BACKGROUND:

Rivastigmine patch (4.6, 9.5 and 13.3 mg/24h) is approved for treatment of mild-to-moderate AD. Data suggest rivastigmine 13.3 mg/24h patch is efficacious at more advanced disease stages.

DESIGN/METHODS:

ACTION was a 24-week, prospective, randomized, double-blind, multicenter study in patients with severe AD. Patients aged ≥50 years, with probable AD and Mini-Mental State Examination (MMSE) score of ≥3-≤12, were randomized (13.3 or 4.6 mg/24h patch). Co-primary outcomes were change from baseline at Week 24 on AD Cooperative Study-Activities of Daily Living scale-Severe Impairment Version (ADCS-ADL-SIV) and Severe Impairment Battery (SIB) in the Modified Full Analysis Set (MFAS), using a last observation carried forward (LOCF) approach. Sensitivity analysis included efficacy on co-primary outcomes using a pattern mixture model. ADCS-Clinical Global Impression of Change (ADCS-CGIC), 12-item Neuropsychiatric Inventory (NPI-12), safety and tolerability were secondary assessments.

RESULTS:

Patients were randomized to 13.3 (n=356) or 4.6 mg/24h patch (n=360). Baseline characteristics and demographics were comparable. A similar proportion of both groups completed the study. Significantly less deterioration was observed on ADCS-ADL-SIV and SIB with 13.3 versus 4.6 mg/24h patch in the primary LOCF (p=0.0247 and p<0.0001, respectively) and sensitivity analyses (p=0.0161 and p<0.0001). Significant differences, in favor of high-dose patch, were observed on ADCS-CGIC (p=0.0023), but not NPI-12. The incidence of adverse events (AE) and serious AE (SAE) was comparable with 13.3 and 4.6 mg/24h patch (AE, 74.6% and 73.3%; SAE, 14.9% and 13.6%). Discontinuation due to AE and SAE was higher with 13.3 than 4.6 mg/24h patch (AE, 13.5% and 10.9%; SAE, 8.2% and 4.5%).

CONCLUSIONS:

13.3 mg/24h rivastigmine patch showed benefit over 4.6 mg/24h on ADL and cognition in patients with severe AD. Preliminary safety review of 13.3 mg/24h patch appears consistent with previous studies.