Gantenerumab for early Alzheimer’s disease: a systematic review and meta-analysis

ABSTRACT

Introduction

Gantenerumab is a monoclonal antibody targeting amyloid β protein (Aβ) in early Alzheimer’s disease (AD). The authors sought to evaluate gantenerumab safety and efficacy in early AD patients.

Methods

MEDLINE, Embase, and Cochrane databases were systematically searched until 2 December 2023. Data were examined using the Mantel–Haenszel method and 95% confidence intervals (CIs). Meta-regression analysis was conducted to evaluate a possible link between baseline Clinical Dementia Rating Scale – Sum of Boxes (CDR-SB) and amyloid-related imaging abnormalities (ARIA) at follow-up. R, version 4.2.3, was used for statistical analysis.

Results

A total of 4 RCTs and 2848 patients were included, of whom 1580 (55%) received subcutaneous gantenerumab. Concerning clinical scores, the placebo group achieved better rates of change in the Disease Assessment Scale (ADAS-Cog13) (SMD −0.11; 95% CI −0.19– −0.03; p = 0.008569; I² = 0%). Gantenerumab was strongly associated with the occurrence of ARIA-E and ARIA-H: (19.67% vs. 2.31%; RR 9.46; 95% CI 5.55–16.11; p = <0.000001; I² = 10%) and (21.95% vs. 12.38%; RR 1.79; 95% CI 1.50–2.13; p = <0.000001; I² = 0%), respectively.

Discussion

In this meta-analysis, consistent results suggest that gantenerumab is not safe and efficient for early AD, showing no improvement in clinical scores for AD and being associated with the occurrence of ARIA-E and ARIA-H.

KEYWORDS:

• Alzheimer’s disease
• monoclonal antibodies
• early alzheimer’s disease
• disease-modifying treatment
• gantenerumab

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

All authors made substantial contributions to the conception or design of the work or the acquisition, analysis, or interpretation of data for the work: A Menegaz de Almeida and M Leite conceived the research question, elaborated the search strategy, and conducted the study selection; P Gomes Lima, ML Siegloch Barros, and S Rocha Pinheiro contributed to conducting data acquisition. A Menegaz de Almeida, LM Lopes., and I Andrade conducted the interpretation of the data and A Menegaz de Almeida synthesized the data using statistics software; A Menegaz de Almeida and P Viana assessed the risk of bias; A Menegaz de Almeida, M Leite, LM Lopes, V Morbach, and G Marinheiro drafted the writing. All authors reviewed it for important intellectual content and R de Oliveira and AC Pinheiro reviewed it critically as specialists in the field. All authors reviewed and approved the final version for publication and can confirm that they meet the ICMJE authorship criteria.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14737175.2024.2367016

Additional information

Funding

This paper was not funded.