Efficacy of brexpiprazole on frequently occurring agitation behaviors in patients with dementia due to Alzheimer’s disease: post hoc pooled analysis of two randomized controlled trials

Abstract

Introduction Conclusions Results Methods • Patients with agitation associated with dementia due to Alzheimer's disease exhibit a broad range of frequently occurring agitation behaviors. • In this post hoc analysis of patients with frequently occurring agitation behaviors, fixed-dose brexpiprazole 2 or 3 mg/day was associated with a numerically greater reduction in the frequency of most behaviors versus placebo. Sunday-550 • Agitation symptoms are highly prevalent in patients with Alzheimer's dementia. 1,2 • Agitation symptoms can manifest in a variety of forms, including non-aggressive and aggressive behaviors, 3 and individual behaviors can occur at varying frequencies. 2,4,5 • Brexpiprazole, which acts on noradrenergic, serotonergic, and dopaminergic neurotransmitter systems, 6 is approved in the US and Canada for the treatment of agitation associated with dementia due to Alzheimer's disease. 7,8 • The efficacy of brexpiprazole on 29 individual agitation behaviors (Cohen-Mansfield Agitation Inventory [CMAI] items) was previously evaluated in two trials of patients with agitation associated with dementia due to Alzheimer's disease. 9 There were numerically greater reductions in the frequency of most individual agitation behaviors with brexpiprazole versus placebo. 9 • The previous analysis was conducted in the full efficacy sample of each trial, regardless of patients' baseline behavior frequencies. 9 To explore meaningful effectiveness on agitation behavior frequency, it is beneficial to study subgroups of patients in whom behaviors are present at baseline. • The aim of this pooled post hoc analysis was to determine the efficacy of fixed-dose brexpiprazole on the same individual agitation behaviors, now specifically focusing on patients who were frequently experiencing the behaviors at baseline, using all available data. Patients • The total pooled sample comprised 610 patients (brexpiprazole, n=363; placebo, n=247). • Baseline demographic and clinical characteristics have been presented previously, and were generally similar between treatment groups in each trial. 10,11 • At baseline, in the total pooled sample, the mean (standard deviation) number of different CMAI agitation behaviors occurring at least weekly was 12.8 (4.3) per patient. • At baseline, the agitation behaviors most commonly occurring at least weekly were general restlessness (n=572), pacing/aimless wandering (n=513), and cursing or verbal aggression (n=496) (Figure 2). • For some behaviors (e.g., intentional falling, n=27), conclusions are limited by small subsample sizes. Change in CMAI item scores from baseline to Week 12 • Figure 3 shows the change in CMAI item scores between baseline and Week 12, in subsamples of patients for whom the corresponding behavior occurred at least once per week at baseline (CMAI item score ≥3). • A greater numerical reduction for brexpiprazole versus placebo was observed on 24/29 items (Figure 3). • Data were pooled from two Phase 3, multicenter, 12-week, randomized, double-blind, placebo-controlled, parallel-arm, fixed-dose trials in patients with agitation associated with dementia due to Alzheimer's disease (ClinicalTrials.gov identifiers: NCT01862640 [Study 283]; 10 NCT03548584 [Study 213] 11) (Figure 1). • The primary efficacy endpoint of each trial was the change from baseline to Week 12 in CMAI Total score. 10,11 • The CMAI evaluates the frequency of 29 agitated behaviors (Box 1), with a total score range of 29-203. 12,13 • In this post hoc analysis, the change from baseline to Week 12 in each CMAI item score was determined in subsamples of patients for whom the corresponding behavior occurred at least once per week (item score ≥3) at baseline. • Data were pooled for brexpiprazole 2 or 3 mg/day (FDA-approved dose) 7 and for placebo. • Data are reported using descriptive statistics for patients who completed 12 weeks of treatment.