The rivastigmine high-dose, 13 mg/24h (15cm2), transdermal patch provides daily living benefits to people with severe Alzheimer's disease: Retrospective analyses of the optimising transdermal exelon in mild-to-moderate Alzheimer's disease (OPTIMA) study

Background: The OPTIMA study (NCT00506415) provided the unique opportunity to investigate outcomes of treatmentwith 13.3mg/24h (15cm2) versus 9.5 mg/24h (10cm 2) rivastigmine patch, in different patient populations. Efficacy on theAlzheimer's Disease Co-operative Study-InstrumentalActivities of Daily Living (ADCS-IADL) scale was a co-primary study endpoint. The aimof this analysiswas to compare outcomes on function and tolerability of the two patch doses in a severe patient subpopulation. Methods: OPTIMA was a randomized, multicenter, parallel-group, double-blind study. Patients (aged 50V'85 years) meeting pre-specified criteria for functional and cognitive decline, during a 24-48 week, initial open-label phase with 9.5 mg/24h rivastigmine patch, entered a 48-week, double-blind (DB) phase and were randomized to receive 13.3 mg/24h or 9.5 mg/24h patch. Retrospective analyses were performed on changes from DB-baseline toWeek 48 on individual items of the ADCS-IADL scale and reported incidences of adverse events (AEs), within a defined subpopulation with severe AD (Mini-Mental State Examination score ≤ 12 [comparable with other rivastigmine trials in patients with severe AD]). Results: At DB-baseline, 93 patients randomized to 13.3 mg/24h patch and 86 patients randomized to 9.5 mg/24h patch had progressed to severe AD. On the ADCS-IADL scale, numerically, less decline was displayed on 15/17 items atWeek 48 in the 13.3 mg/24h versus 9.5 mg/24h patch group, with statistical significance (p<0.05) reached for four items at this time-point (watching television, travel, being left alone and using household appliances), and for 10/17 items at one or more time-points during the DBphase. The most commonly reported AEs, in this subpopulation for the 13.3 mg/24h versus 9.5 mg/24h patch group, respectively, were: psychiatric disorders (33% vs 24%), nervous systemdisorders (26% vs 20%), and gastrointestinal disorders (19% vs 23%). Fewer patients discontinued treatment with the 13.3 mg/24h compared with the 9.5 mg/24h patch (8% vs 16%). Conclusions: In this OPTIMA study subpopulation with severe AD, the high-dose, 13.3 mg/24h rivastigmine patch remained well tolerated and demonstrated additional benefit compared with 9.5 mg/24h, on activities of daily living items that impact quality of life and degree of independence.