P3‐424: High‐dose 13.3 mg/24 h rivastigmine transdermal patch demonstrates efficacy on instrumental activities of daily living: Individual item analysis

Background: OPTIMA, a 48-week randomized, double-blind (DB) study, compared the efficacy and safety of 13.3 and 9.5 mg/24 h rivastigmine patches in patients with AD meeting functional and cognitive decline criteria during an initial open-label (IOL) phasewith 9.5 mg/24 h patch. The current analysis investigated the efficacy of 13.3 mg/24 h patch on the autonomy in instrumental activities of daily living (IADL) in patients by disease severity and time-to-meet decline criteria.Methods: Patients receiving rivastigmine patch 9.5 mg/24 h, were assessed at Weeks 24, 36 and 48 of the IOL phase for functional (investigators’ judgement) and cognitive decline ( 2-point decrease in Mini-Mental State Examination [MMSE] score from previous visit OR 3-point decrease from baseline). Decliners entered the randomized DB phase (9.5 or 13.3 mg/24 h). Co-primary outcomes included change from DB-baseline at Week 48 on the AD Cooperative Study (ADCS)-IADL scale. Prospective subgroup analyses were efficacy on ADCS-IADL by: disease severity at DB-baseline (moderate [MMSE 10 18] versus moderate-to-severe [MMSE 3 18]); and time-to-meet decline criteria ( 36 versus >36 weeks). Results: The mean DB-baseline ADCS-IADL score was higher with 13.3 mg/24 h, compared with 9.5 mg/ 24 h patch, for patients with moderate (26.7 and 24.5, respectively) or moderate-to-severe disease (25.3 and 22.8, respectively). At all time points, regardless of disease severity, slower decline in ADCS-IADL score was observed with 13.3 versus 9.5 mg/24 h patch. The mean DB-baseline ADCS-IADL score was higher with 13.3 mg/24 h, compared with 9.5 mg/ 24 h patch, for patients meeting decline criteria 36 weeks (27.1 and 24.5, respectively), but comparable for patients meeting decline criteria >36 weeks. Regardless of time-to-meet decline criteria, decline in ADCS-IADL score was less with 13.3 mg/24 h patch during Weeks 16 to 48.The superiority of the 13.3 mg/24 h patch compared with the 9.5 mg/ 24 h patch was confirmed by statistical comparisons adjusted for the corresponding baseline value for the different subgroup analyses. Conclusions: High-dose (13.3 mg/24 h) rivastigmine patch demonstrates superior efficacy on functional outcomes and provides additional benefits to patients with AD, compared with 9.5 mg/24 h patch, regardless of their disease severity or time-to-meet decline criteria.