Efficacy of Brexpiprazole in Patients with Agitation Associated with Dementia Due to Alzheimer's Disease Analyzed by Patient Characteristics: A Post Hoc Pooled Analysis of Randomized, Fixed-Dose, Placebo-Controlled Trials

IntroductionBrexpiprazole is an efficacious and well-tolerated treatment for agitation associated with dementia due to Alzheimer's disease. To assist with treatment decision-making, it is valuable to explore treatment effects in different patient subgroups. These post hoc subgroup analyses explored the efficacy of brexpiprazole in patients with agitation associated with dementia due to Alzheimer's disease according to dementia severity, co-occurring neuropsychiatric symptoms, concomitant use of treatments for dementia or psychiatric conditions, and care setting.MethodsThis was a post hoc analysis of efficacy data from two 12-week, Phase 3, randomized, placebo-controlled trials of fixed-dose brexpiprazole in patients with agitation associated with dementia due to Alzheimer's disease (NCT01862640, NCT03548584). Data were pooled for brexpiprazole 2 or 3 mg/day treatment arms, and separately for placebo arms. Change in Cohen-Mansfield Agitation Inventory (CMAI) Total score from baseline to Week 12 (primary endpoint in each trial) was analyzed using a mixed model for repeated measures. Least squares mean change from baseline was compared between brexpiprazole and placebo arms in each subgroup. Responder analyses were also conducted, based on a meaningful within-patient change threshold of ≥20-point reduction from baseline to Week 12 in CMAI Total score. Baseline dementia severity was classed as mild/moderate (Mini Mental State Examination score ≥13) or severe (score ≤12). Presence of baseline co-occurring neuropsychiatric symptoms was defined as reported history of each of 11 neuropsychiatric symptoms associated with Alzheimer's disease at the screening visit. Concomitant use of treatments for dementia or psychiatric conditions was defined as use of memantine, cholinesterase inhibitor, or antidepressant during the trials, or a history of benzodiazepine or anxiolytic use prior to the trials. Setting was defined as community-based or long-term care facility.ResultsThe analysis included 610 patients: 363 who received brexpiprazole 2 or 3 mg/day and 247 who received placebo. The least squares mean change in CMAI Total score at Week 12 was larger with brexpiprazole than placebo in subgroups with mild/moderate dementia and severe dementia. Similarly, brexpiprazole was associated with a larger change from baseline to Week 12 in CMAI Total score than placebo in all subgroups with and without co-occurring neuropsychiatric symptoms, and in all subgroups with and without concomitant use of treatments for dementia or psychiatric conditions. Brexpiprazole also showed a larger change in CMAI Total score at Week 12 than placebo in the subgroups based in the community and in long-term care facilities. Overall, a greater proportion of patients treated with brexpiprazole achieved meaningful response compared to placebo, across different studied subgroups. These analyses are limited by small sample sizes for certain subgroups.ConclusionsIn patients with agitation associated with dementia due to Alzheimer's disease, the effect of brexpiprazole on symptoms of agitation was consistent across different patient subgroups. Brexpiprazole showed larger improvement than placebo, and higher response rates based on a meaningful within-patient change threshold, regardless of dementia severity, presence or absence of co-occurring neuropsychiatric symptoms, use of concomitant treatments for dementia or psychiatric conditions, and care setting.