Impact of dementia severity on efficacy of brexpiprazole for agitation in Alzheimer's dementia: A post hoc analysis of a randomized, double-blind, placebo-controlled study in Japan

Background The impact of dementia severity on the efficacy of brexpiprazole for agitation associated with Alzheimer's disease in Japanese patients remains unclear. Objective This post hoc analysis aimed to further examine the efficacy of brexpiprazole with respect to the severity of Alzheimer's dementia (AD), determined using Mini-Mental State Examination (MMSE) score, in a randomized, double-blind, placebo-controlled study conducted in Japanese patients with agitation in AD (AAD). Methods Data from Japanese patients with AAD who received brexpiprazole 1 mg/day or 2 mg/day, or placebo for 10 weeks were analyzed. Changes from baseline in Cohen-Mansfield Agitation Inventory (CMAI) total score were evaluated according to severity of dementia (mild-to-moderate AD: MMSE 11-22; severe AD: MMSE 1–10). Changes from baseline in Clinical Global Impression-Severity of Illness (CGI-S) score were similarly assessed. Results At Week 10, greater improvement was observed primarily with brexpiprazole compared with placebo, whereas efficacy in severe AD was limited with the 1 mg dose. Differences between brexpiprazole and placebo in the mean change from baseline in CMAI total score for mild-to-moderate and severe AD groups were −4.2 (p = 0.0306) and −2.9 (p = 0.2534) for brexpiprazole 1 mg, −7.0 (p = 0.0001) and −7.3 (p = 0.0024) for brexpiprazole 2 mg, respectively. Differences in CGI-S score were −0.3 (p = 0.0598) and −0.4 (p = 0.0762) in brexpiprazole 1 mg, −0.8 (p < 0.0001) and −0.7 (p = 0.0002) in brexpiprazole 2 mg, respectively. Conclusions Brexpiprazole showed efficacy at the 2 mg dose in Japanese patients, supporting its effectiveness for AAD across AD severities; the effects of the 1 mg dose in severe AD were limited. ClinicalTrials.gov Identifier NCT03620981 (trial registry name: Brexpiprazole for the Treatment of Patients With Agitation Associated With Dementia of the Alzheimer's Type). Available from https://www.clinicaltrials.gov/study/NCT03620981 .