Efficacy and safety of idalopirdine for Alzheimer's disease: A systematic review and meta-Analysis

Shinji Matsunaga, Hiroshige Fujishiro, Hajime Takechi

研究成果: Article

抄録

Objective: The efficacy and tolerability of idalopirdine, a selective 5-hydroxytryptamine6 receptor antagonist, in patients with Alzheimer's disease (AD) is uncertain. A systematic review and meta-Analysis of randomized controlled trials (RCTs) testing idalopirdine for patients with AD was performed.Methods: We included RCTs of idalopirdine for patients with AD and used Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) scores as a primary measure.Results: Four RCTs with 2,803 patients with AD were included. There was no significant difference in ADAS-cog between the idalopirdine and placebo groups [mean difference (MD) =-0.41, P = 0.32, I 2 = 62%]. However, significant heterogeneity remained. Sensitivity analysis revealed that idalopirdine was more effective than placebo for ADAS-cog in the high dose and moderate AD subgroups (high dose subgroup: MD =-2.15, P = 0.005, moderate AD subgroup: MD =-2.15, P = 0.005). Moreover, meta-regression analysis showed that idalopirdine effect size for ADAS-cog was associated with mean dose (coefficient,-0.0289), ADAS-cog at baseline (coefficient,-0.9519), and proportion of male participants (coefficient, 0.2214). For safety outcomes, idalopirdine was associated with a higher incidence of at least one adverse event and increased γ-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, and vomiting than placebo. There were no significant differences in other secondary outcomes between both treatments.Conclusions: Idalopirdine is not effective for AD patients and is associated with a risk of elevated liver enzymes and vomiting. Although idalopirdine might be more effective at high doses and in moderate AD subgroups, the effect size is small and may be limited.

元の言語English
ページ(範囲)1627-1633
ページ数7
ジャーナルInternational Psychogeriatrics
31
発行部数11
DOI
出版物ステータスPublished - 01-11-2019

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Meta-Analysis
Alzheimer Disease
Safety
Randomized Controlled Trials
Placebos
(2-(6-fluoro-1H-indol-3-yl)-ethyl)-(3-(2,2,3,3-tetrafluoropropoxy)benzyl)amine
Vomiting
Aspartate Aminotransferases
Alanine Transaminase
Regression Analysis

All Science Journal Classification (ASJC) codes

  • Clinical Psychology
  • Gerontology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

これを引用

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title = "Efficacy and safety of idalopirdine for Alzheimer's disease: A systematic review and meta-Analysis",
abstract = "Objective: The efficacy and tolerability of idalopirdine, a selective 5-hydroxytryptamine6 receptor antagonist, in patients with Alzheimer's disease (AD) is uncertain. A systematic review and meta-Analysis of randomized controlled trials (RCTs) testing idalopirdine for patients with AD was performed.Methods: We included RCTs of idalopirdine for patients with AD and used Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) scores as a primary measure.Results: Four RCTs with 2,803 patients with AD were included. There was no significant difference in ADAS-cog between the idalopirdine and placebo groups [mean difference (MD) =-0.41, P = 0.32, I 2 = 62{\%}]. However, significant heterogeneity remained. Sensitivity analysis revealed that idalopirdine was more effective than placebo for ADAS-cog in the high dose and moderate AD subgroups (high dose subgroup: MD =-2.15, P = 0.005, moderate AD subgroup: MD =-2.15, P = 0.005). Moreover, meta-regression analysis showed that idalopirdine effect size for ADAS-cog was associated with mean dose (coefficient,-0.0289), ADAS-cog at baseline (coefficient,-0.9519), and proportion of male participants (coefficient, 0.2214). For safety outcomes, idalopirdine was associated with a higher incidence of at least one adverse event and increased γ-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, and vomiting than placebo. There were no significant differences in other secondary outcomes between both treatments.Conclusions: Idalopirdine is not effective for AD patients and is associated with a risk of elevated liver enzymes and vomiting. Although idalopirdine might be more effective at high doses and in moderate AD subgroups, the effect size is small and may be limited.",
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Efficacy and safety of idalopirdine for Alzheimer's disease : A systematic review and meta-Analysis. / Matsunaga, Shinji; Fujishiro, Hiroshige; Takechi, Hajime.

:: International Psychogeriatrics, 巻 31, 番号 11, 01.11.2019, p. 1627-1633.

研究成果: Article

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T1 - Efficacy and safety of idalopirdine for Alzheimer's disease

T2 - A systematic review and meta-Analysis

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AU - Fujishiro, Hiroshige

AU - Takechi, Hajime

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Objective: The efficacy and tolerability of idalopirdine, a selective 5-hydroxytryptamine6 receptor antagonist, in patients with Alzheimer's disease (AD) is uncertain. A systematic review and meta-Analysis of randomized controlled trials (RCTs) testing idalopirdine for patients with AD was performed.Methods: We included RCTs of idalopirdine for patients with AD and used Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) scores as a primary measure.Results: Four RCTs with 2,803 patients with AD were included. There was no significant difference in ADAS-cog between the idalopirdine and placebo groups [mean difference (MD) =-0.41, P = 0.32, I 2 = 62%]. However, significant heterogeneity remained. Sensitivity analysis revealed that idalopirdine was more effective than placebo for ADAS-cog in the high dose and moderate AD subgroups (high dose subgroup: MD =-2.15, P = 0.005, moderate AD subgroup: MD =-2.15, P = 0.005). Moreover, meta-regression analysis showed that idalopirdine effect size for ADAS-cog was associated with mean dose (coefficient,-0.0289), ADAS-cog at baseline (coefficient,-0.9519), and proportion of male participants (coefficient, 0.2214). For safety outcomes, idalopirdine was associated with a higher incidence of at least one adverse event and increased γ-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, and vomiting than placebo. There were no significant differences in other secondary outcomes between both treatments.Conclusions: Idalopirdine is not effective for AD patients and is associated with a risk of elevated liver enzymes and vomiting. Although idalopirdine might be more effective at high doses and in moderate AD subgroups, the effect size is small and may be limited.

AB - Objective: The efficacy and tolerability of idalopirdine, a selective 5-hydroxytryptamine6 receptor antagonist, in patients with Alzheimer's disease (AD) is uncertain. A systematic review and meta-Analysis of randomized controlled trials (RCTs) testing idalopirdine for patients with AD was performed.Methods: We included RCTs of idalopirdine for patients with AD and used Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) scores as a primary measure.Results: Four RCTs with 2,803 patients with AD were included. There was no significant difference in ADAS-cog between the idalopirdine and placebo groups [mean difference (MD) =-0.41, P = 0.32, I 2 = 62%]. However, significant heterogeneity remained. Sensitivity analysis revealed that idalopirdine was more effective than placebo for ADAS-cog in the high dose and moderate AD subgroups (high dose subgroup: MD =-2.15, P = 0.005, moderate AD subgroup: MD =-2.15, P = 0.005). Moreover, meta-regression analysis showed that idalopirdine effect size for ADAS-cog was associated with mean dose (coefficient,-0.0289), ADAS-cog at baseline (coefficient,-0.9519), and proportion of male participants (coefficient, 0.2214). For safety outcomes, idalopirdine was associated with a higher incidence of at least one adverse event and increased γ-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, and vomiting than placebo. There were no significant differences in other secondary outcomes between both treatments.Conclusions: Idalopirdine is not effective for AD patients and is associated with a risk of elevated liver enzymes and vomiting. Although idalopirdine might be more effective at high doses and in moderate AD subgroups, the effect size is small and may be limited.

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