Efficacy, safety and tolerability of rivastigmine patch 13.3 mg/24 h (15 cm2) versus 4.6 mg/24 h (5 cm2) in patients with severe Alzheimer's disease: results of the ACTivities of daily living and cognitION (ACTION) study

Abstract

Rivastigmine transdermal patch (4.6 mg/24 h and 9.5 mg/24 h) is currently approved for the symptomatic treatment of mild-to-moderate Alzheimer's disease (AD). Data suggest rivastigmine may also be efficacious at more advanced disease stages and at higher doses. The ACTivities of daily living and cognitION (ACTION) study investigated the benefit/risk of a higher-dose rivastigmine patch in patients with severe AD. ACTION was a 24-week, prospective, randomized, double-blind, multicenter study of 13.3 mg/24 h versus 4.6 mg/24 h patch in patients with severe AD. Patients aged ≥ 50 years, with a diagnosis of probable AD and a Mini-Mental State Examination score of 3-12 were randomized to 13.3 mg/24 h or 4.6 mg/24 h patch. Co-primary outcome assessments were the change from baseline at Week 24 on the Alzheimer's Disease Cooperative Study-Activities of Daily Living scale-Severe Impairment Version (ADCS-ADL-SIV) and the Severe Impairment Battery (SIB). Secondary outcome assessments included the ADCS-Clinical Global Impression of Change (ADCS-CGIC) and the 12-item Neuropsychiatric Inventory (NPI-12). Safety and tolerability were also assessed. In total, 716 patients were randomized to the study drug; n = 356 to 13.3 mg/24 h patch and n = 360 to 4.6 mg/24 h patch. Similar proportions of patients in both groups completed the study (13.3 mg/24 h, 64.3%; 4.6 mg/24 h, 65.0%). Baseline characteristics and demographics were comparable. Significantly less deterioration was observed on the ADCS-ADL-SIV and SIB with 13.3 mg/24 h versus 4.6 mg/24 h patch (p = 0.0247 and p < 0.0001, respectively). Significant differences, in favor of the 13.3 mg/24 h patch, were observed on the ADCS-CGIC (p = 0.0023 versus 4.6 mg/24 h); there were no significant between-dose differences on the NPI-12. The incidence of adverse events (AE) and serious AE (SAE) was comparable between the 13.3 mg/24 h and 4.6 mg/24 h patch groups (AE, 74.6% and 73.3%; SAE, 14.9% and 13.6%). The most common AE were psychiatric (31.0%; 26.7%), and skin and subcutaneous tissue disorders (25.6%; 26.2%). Discontinuation due to AE and SAE was higher with 13.3 mg/24 h than 4.6 mg/24 h patch (AE, 13.5% and 10.9%; SAE, 8.2% and 4.5%). The 13.3 mg/24 h rivastigmine patch showed benefit over the 4.6 mg/24 h patch on ADLs and cognition at Week 24 in this population with severe AD. Preliminary safety review of 13.3 mg/24 h patch appears to be consistent with that observed in previous studies.