Alpesh Shah, Alvin Estilo, Pamela L Sheridan, Uwa Kalu, Dalei Chen, Denise Chang, Mary Slomkowski, Daniel Lee, Nanco Hefting, Mary Hobart, Saloni Behl, Pedro Such, Malaak Brubaker, George T Grossberg
{"title":"Brexpiprazole对阿尔茨海默病痴呆相关躁动患者的安全性和耐受性：三个随机试验和一项扩展试验的汇总分析","authors":"Alpesh Shah, Alvin Estilo, Pamela L Sheridan, Uwa Kalu, Dalei Chen, Denise Chang, Mary Slomkowski, Daniel Lee, Nanco Hefting, Mary Hobart, Saloni Behl, Pedro Such, Malaak Brubaker, George T Grossberg","doi":"10.1007/s40263-025-01200-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objective: </strong>Older adults with dementia are particularly vulnerable to antipsychotic side effects. Brexpiprazole, an atypical antipsychotic, is approved in a number of countries for the treatment of agitation associated with dementia due to Alzheimer's disease. This pooled analysis aimed to evaluate the safety and tolerability of brexpiprazole in this patient population.</p><p><strong>Methods: </strong>Data were included from three Phase 3, 12-week, randomized, double-blind, placebo-controlled trials and a Phase 3, 12-week, active-treatment extension trial in participants with agitation associated with dementia due to Alzheimer's disease. Safety outcomes included treatment-emergent adverse events (TEAEs), weight change, suicidality, extrapyramidal symptoms, and cognitive dysfunction. Two datasets were considered: a 12-week dataset that pooled data from the three randomized trials for brexpiprazole 0.5-3 mg/day and placebo, and a 24-week dataset that combined data from the parent randomized trial and the extension trial for brexpiprazole 2-3 mg/day.</p><p><strong>Results: </strong>Over 12 weeks, 335/655 (51.1%) participants on brexpiprazole and 178/388 (45.9%) participants on placebo reported ≥ 1 TEAE, which led to discontinuation in 41 (6.3%) and 13 (3.4%) participants, respectively. Headache was the only TEAE with incidence ≥ 5% (brexpiprazole, 50 [7.6%] participants; placebo, 36 [9.3%] participants). The incidences of cerebrovascular TEAEs (brexpiprazole, 0.5%; placebo, 0.3%), cardiovascular TEAEs (3.7%; 2.3%), extrapyramidal symptom-related TEAEs (5.3%; 3.1%), and somnolence/sedation TEAEs (3.7%; 1.8%) were generally similar between treatment groups. Six (0.9%) participants on brexpiprazole and 1 (0.3%) participant on placebo died; causes of death were not considered related to brexpiprazole and were generally in line with those expected in Alzheimer's disease. Over 24 weeks, 110/226 (48.7%) participants on brexpiprazole reported ≥ 1 TEAE, which led to discontinuation in 19 (8.4%) participants. Headache was the only TEAE with incidence ≥ 5% (18 [8.0%] participants). No participants died during the extension trial. Over 12 and 24 weeks, mean changes in weight, suicidality, and extrapyramidal symptoms were minimal, with no worsening of cognition.</p><p><strong>Conclusions: </strong>Considering pooled data from > 1000 participants on brexpiprazole or placebo, brexpiprazole appears to be generally well tolerated for up to 24 weeks in participants with agitation associated with dementia due to Alzheimer's disease.</p><p><strong>Study registration: </strong>ClinicalTrials.gov identifiers: NCT01862640, NCT01922258, NCT03548584, NCT03594123.</p>","PeriodicalId":10508,"journal":{"name":"CNS drugs","volume":" ","pages":""},"PeriodicalIF":7.4000,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Safety and Tolerability of Brexpiprazole in Participants with Agitation Associated with Dementia due to Alzheimer's Disease: Pooled Analysis of Three Randomized Trials and an Extension Trial.\",\"authors\":\"Alpesh Shah, Alvin Estilo, Pamela L Sheridan, Uwa Kalu, Dalei Chen, Denise Chang, Mary Slomkowski, Daniel Lee, Nanco Hefting, Mary Hobart, Saloni Behl, Pedro Such, Malaak Brubaker, George T Grossberg\",\"doi\":\"10.1007/s40263-025-01200-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background and objective: </strong>Older adults with dementia are particularly vulnerable to antipsychotic side effects. 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Two datasets were considered: a 12-week dataset that pooled data from the three randomized trials for brexpiprazole 0.5-3 mg/day and placebo, and a 24-week dataset that combined data from the parent randomized trial and the extension trial for brexpiprazole 2-3 mg/day.</p><p><strong>Results: </strong>Over 12 weeks, 335/655 (51.1%) participants on brexpiprazole and 178/388 (45.9%) participants on placebo reported ≥ 1 TEAE, which led to discontinuation in 41 (6.3%) and 13 (3.4%) participants, respectively. Headache was the only TEAE with incidence ≥ 5% (brexpiprazole, 50 [7.6%] participants; placebo, 36 [9.3%] participants). The incidences of cerebrovascular TEAEs (brexpiprazole, 0.5%; placebo, 0.3%), cardiovascular TEAEs (3.7%; 2.3%), extrapyramidal symptom-related TEAEs (5.3%; 3.1%), and somnolence/sedation TEAEs (3.7%; 1.8%) were generally similar between treatment groups. Six (0.9%) participants on brexpiprazole and 1 (0.3%) participant on placebo died; causes of death were not considered related to brexpiprazole and were generally in line with those expected in Alzheimer's disease. Over 24 weeks, 110/226 (48.7%) participants on brexpiprazole reported ≥ 1 TEAE, which led to discontinuation in 19 (8.4%) participants. Headache was the only TEAE with incidence ≥ 5% (18 [8.0%] participants). No participants died during the extension trial. 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Safety and Tolerability of Brexpiprazole in Participants with Agitation Associated with Dementia due to Alzheimer's Disease: Pooled Analysis of Three Randomized Trials and an Extension Trial.
Background and objective: Older adults with dementia are particularly vulnerable to antipsychotic side effects. Brexpiprazole, an atypical antipsychotic, is approved in a number of countries for the treatment of agitation associated with dementia due to Alzheimer's disease. This pooled analysis aimed to evaluate the safety and tolerability of brexpiprazole in this patient population.
Methods: Data were included from three Phase 3, 12-week, randomized, double-blind, placebo-controlled trials and a Phase 3, 12-week, active-treatment extension trial in participants with agitation associated with dementia due to Alzheimer's disease. Safety outcomes included treatment-emergent adverse events (TEAEs), weight change, suicidality, extrapyramidal symptoms, and cognitive dysfunction. Two datasets were considered: a 12-week dataset that pooled data from the three randomized trials for brexpiprazole 0.5-3 mg/day and placebo, and a 24-week dataset that combined data from the parent randomized trial and the extension trial for brexpiprazole 2-3 mg/day.
Results: Over 12 weeks, 335/655 (51.1%) participants on brexpiprazole and 178/388 (45.9%) participants on placebo reported ≥ 1 TEAE, which led to discontinuation in 41 (6.3%) and 13 (3.4%) participants, respectively. Headache was the only TEAE with incidence ≥ 5% (brexpiprazole, 50 [7.6%] participants; placebo, 36 [9.3%] participants). The incidences of cerebrovascular TEAEs (brexpiprazole, 0.5%; placebo, 0.3%), cardiovascular TEAEs (3.7%; 2.3%), extrapyramidal symptom-related TEAEs (5.3%; 3.1%), and somnolence/sedation TEAEs (3.7%; 1.8%) were generally similar between treatment groups. Six (0.9%) participants on brexpiprazole and 1 (0.3%) participant on placebo died; causes of death were not considered related to brexpiprazole and were generally in line with those expected in Alzheimer's disease. Over 24 weeks, 110/226 (48.7%) participants on brexpiprazole reported ≥ 1 TEAE, which led to discontinuation in 19 (8.4%) participants. Headache was the only TEAE with incidence ≥ 5% (18 [8.0%] participants). No participants died during the extension trial. Over 12 and 24 weeks, mean changes in weight, suicidality, and extrapyramidal symptoms were minimal, with no worsening of cognition.
Conclusions: Considering pooled data from > 1000 participants on brexpiprazole or placebo, brexpiprazole appears to be generally well tolerated for up to 24 weeks in participants with agitation associated with dementia due to Alzheimer's disease.
Study registration: ClinicalTrials.gov identifiers: NCT01862640, NCT01922258, NCT03548584, NCT03594123.
期刊介绍：
CNS Drugs promotes rational pharmacotherapy within the disciplines of clinical psychiatry and neurology. The Journal includes:
- Overviews of contentious or emerging issues.
- Comprehensive narrative reviews that provide an authoritative source of information on pharmacological approaches to managing neurological and psychiatric illnesses.
- Systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement.
- Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in neurology and psychiatry.
- Original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies.
Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in CNS Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.
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