Title | Pharmacological Agents Targeting γ-Secretase Increase Risk of Cancer and Cognitive Decline in Alzheimer's Disease Patients: A Systematic Review and Meta-Analysis. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Penninkilampi, R, Brothers, HM, Eslick, GD |
Journal | J Alzheimers Dis |
Volume | 53 |
Issue | 4 |
Pagination | 1395-404 |
Date Published | 2016 Jul 06 |
ISSN | 1875-8908 |
Abstract | BACKGROUND: Drugs targeting γ-secretase in Alzheimer's disease (AD) have failed to demonstrate efficacy in clinical trials. OBJECTIVE: To perform a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of drugs targeting γ-secretase in AD. METHODS: Ten trials were identified involving 5,227 patients using electronic databases and manual review of reference lists. RCTs of at least two weeks duration involving a drug targeting γ-secretase were eligible. The main outcomes examined were adverse events and cognitive measures (ADAS-cog, MMSE, ADCS-ADL, and CDR-sb). A sub-group analysis was performed, excluding the γ-secretase modulator tarenflurbil, to evaluate the safety and efficacy of γ-secretase inhibitors only. RESULTS: There was an increased risk of adverse events (Odds Ratio (OR) 1.38, 95% CI 1.09-1.73; p = 0.01), serious adverse events (OR 1.50, 95% CI 1.22-1.84; p CONCLUSION: The use of γ-secretase inhibitors is associated with significantly increased risk of serious adverse events including skin cancers, and worsening in cognitive indicators. This evidence indicates that γ-secretase may not be an appropriate target for clinical treatment of AD. |
DOI | 10.3233/JAD-160275 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 27392862 |