A Systematic Review and Network Meta Analysis of Pharmacologic Disease-Modifying Therapies for Early Alzheimer's Disease
Author(s)
Heather Eames, BSc (Pharm), MPharm, MSc (Health Econonomics)1, David McConnell, BA, PhD2, Cliona A. Flynn, BSc, MSc2, Sinead O'Neill, PhD2, Marie Harte, MSc2, Belinda Hernandez, PhD2, Caitriona Ni Choitir, BPharm, MPharm, MSc2, Sean Kennelly, MB PhD FRCPI3, Roisin Adams, BPharm, MPharm, PhD2, Laura Mccullagh, BSc, PhD1.
1National Centre for Pharmacoeconomics and Trinity College Dublin, Dublin, Ireland, 2National Centre for Pharmacoeconomics, Dublin, Ireland, 3Tallaght University Hospital, Dublin, Ireland.
1National Centre for Pharmacoeconomics and Trinity College Dublin, Dublin, Ireland, 2National Centre for Pharmacoeconomics, Dublin, Ireland, 3Tallaght University Hospital, Dublin, Ireland.
OBJECTIVES: The treatment landscape for disease modifying therapies (DMTs) for Early Alzheimer’s Dementia (EAD) is rapidly evolving. The safety of these novel DMTs, including the risk of amyloid-related imaging abnormalities (ARIAs), is a key concern to decision makers. The objective of this research is to assess the comparative efficacy and safety of pharmacologic DMTs for AD. Here we report Systematic Literature Review (SLR) results and a preliminary assessment of comparative safety.
METHODS: A SLR was conducted to identify randomized controlled trials (RCTs) in patients with EAD with confirmed AD pathology. Horizon Scanning identified 34 potential AD DMTs which were eligible for inclusion in the SLR. Comparators were standard of care (SoC), which may include acetylcholinesterase inhibitors and/or memantine, or any other listed intervention. The outcome of interest here is Serious Adverse Events (SAEs), which may include ARIA. A Bayesian network meta-analysis (NMA), via the standard contrast-based generalised linear modelling framework, was applied. Analyses were conducted in R (4.4.2) and JAGS (4.3.1) using BUGSnet.
RESULTS: Twelve sources reporting on eight RCTs, investigating six DMTs versus placebo (a proxy for SoC), were identified in the SLR. The incidence of SAEs were reported across all RCTs. All identified RCTs were considered for inclusion in the NMA. Following a feasibility assessment, seven RCTs, investigating five DMTs (lecanemab, donanemab, blarcamesine, ALZT-OP1a/1b, and AGB108) were included in the NMA. Baseline characteristics were similar across all studies included in the NMA. The preferred random-effects model indicated that blarcamesine was associated with the numerically highest relative risk (RR) of SAEs compared to SoC amongst the identified treatments (RR: 1.58, 95% confidence interval: 0.80 to 3.17).
CONCLUSIONS: Several AD DMTs are in the horizon. The RR of SAEs should be considered, when considering alternative AD treatment classes to mitigate the risk of ARIAs.
METHODS: A SLR was conducted to identify randomized controlled trials (RCTs) in patients with EAD with confirmed AD pathology. Horizon Scanning identified 34 potential AD DMTs which were eligible for inclusion in the SLR. Comparators were standard of care (SoC), which may include acetylcholinesterase inhibitors and/or memantine, or any other listed intervention. The outcome of interest here is Serious Adverse Events (SAEs), which may include ARIA. A Bayesian network meta-analysis (NMA), via the standard contrast-based generalised linear modelling framework, was applied. Analyses were conducted in R (4.4.2) and JAGS (4.3.1) using BUGSnet.
RESULTS: Twelve sources reporting on eight RCTs, investigating six DMTs versus placebo (a proxy for SoC), were identified in the SLR. The incidence of SAEs were reported across all RCTs. All identified RCTs were considered for inclusion in the NMA. Following a feasibility assessment, seven RCTs, investigating five DMTs (lecanemab, donanemab, blarcamesine, ALZT-OP1a/1b, and AGB108) were included in the NMA. Baseline characteristics were similar across all studies included in the NMA. The preferred random-effects model indicated that blarcamesine was associated with the numerically highest relative risk (RR) of SAEs compared to SoC amongst the identified treatments (RR: 1.58, 95% confidence interval: 0.80 to 3.17).
CONCLUSIONS: Several AD DMTs are in the horizon. The RR of SAEs should be considered, when considering alternative AD treatment classes to mitigate the risk of ARIAs.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO5
Topic
Clinical Outcomes, Economic Evaluation, Health Technology Assessment
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
Geriatrics, Mental Health (including addition), Neurological Disorders