Evaluating the safety of investigational anti-Alzheimer’s drugs: a comprehensive meta-analysis in the past to current decade

Avaliação da segurança de medicamentos experimentais para Alzheimer: uma meta-análise abrangente das últimas décadas até o período atual

Alzheimer’s disease is a progressive illness that results in the degeneration of neurons with considerable burden. The pharmacological treatments for Alzheimer’s disease include cholinesterase inhibitors, monoclonal antibodies, NMDA receptor antagonists despite having different adverse drug reactions (ADR) alongside the health benefits. Limited data exists for the complete safety evaluation across different classes of anti-Alzheimer’s drugs.

Objective:  The meta-analysis evaluated the severity, frequency and variability of ADR as a result of Alzheimer’s drugs to determine relative safety across various classes.

Methods:  This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with studies derived from the United States National Library of Medicine (PubMed), Embase, Scopus and ClinicalTrials.gov that focus on randomized controlled trials (RCTs) and observational studies which detailed ADRs of anti-Alzheimer’s drugs. Jeffrey’s Amazing Statistics Program (JASP) software was used to conduct heterogeneity assessment (I2), risk ratio (RR) and publication bias analysis in addition to meta-regression.

Results:  31 studies were utilized. The studies with cholinesterase inhibitors exhibited more gastrointestinal ADRs and monoclonal antibodies exhibited amyloid-related imaging abnormalities (ARIA-H and E). The BACE1 inhibitors showed liver toxicity that led to increased patient drug discontinuation. A random-effects model was used for the analysis due to heterogeneity (I²>50%). The meta-regression analysis indicated drug class as a predictor for the type of ADR.

Conclusion:  The research demonstrates considerable variations in the safety of Alzheimer’s drugs that need tailored treatment supported by post-approval monitoring systems. The literature needs extended investigations of safety evaluation as well as practical treatment investigations in actual clinical settings. Unlike conventional reviews focusing solely on currently approved therapies, this study provides a cross-generational analysis of adverse drug reactions across both historical and investigational anti-Alzheimer’s agents, offering insights into mechanism-related safety patterns that may inform the development and clinical use of emerging therapies.

Keywords:
Alzheimer disease; Drug-related side effects and adverse reactions; Meta-analysis; Pharmacovigilance; Antibodies; Monoclonal