Efficacy of Gantenerumab Compared to Placebo in Adults with Alzheimer’s Disease: An Updated Systematic Review and Meta-analysis of Cognitive Function and Amyloid Plaque Reduction
Jawaria Firdous1, Laiba Khalid1, Naila Zainab2, Muhammad Umar Ejaz3, Areeba Tabassum2, zaheer muhammad ahmed2, Tayyaba Abbasi2, Iffah Zafar gondal4, Hamza Ashraf5, Umaimah Naeem2, Muhammad Mohsin Khan2, Atif Malik6, Faseeh Haider7, Syed Inam8
1Punjab Medical College, Faisalabad, Pakistan, 2Jinnah Sindh Medical University, Karachi, Pakistan, 3CMH Lahore medical college, 4Rawal institute of health sciences, 5Allama Iqbal Medical College, Lahore, Pakistan, 6Sheikh Zayed Medical College/Hospital, 7Allama Iqbal Medical College, 8Louisiana State University School of Medicine New Orleans
Objective:
This systematic review and meta-analysis assessed gantenerumab's impact on cognitive and functional outcomes, safety, and biomarker changes in individuals with Alzheimer’s Disease (AD).
Background:
Alzheimer’s Disease (AD) is thought to account for 60-70% of dementia cases globally. The progressive neurodegeneration unique to AD causes terrible cognitive decline, memory loss, and functional impairment. Gantenerumab, a fully human monoclonal antibody, has been explored as a disease-modifying therapy for AD.
Design/Methods:
We conducted a comprehensive literature search of PubMed, Embase, and Cochrane databases from inception to May 25, 2025, for randomized controlled trials (RCTs) comparing gantenerumab to placebo in patients with AD. Review was registered with PROSPERO (CRD420251067883). Data on study characteristics, cognitive and functional efficacy outcomes, and severe adverse events (SAEs) were extracted. Pooled estimates were calculated using a random-effects model in RevMan (v5.4.1).
Results:
A total of seven randomized controlled trials (RCTs) encompassing 6,847 participants were included in this meta-analysis. Gantenerumab was associated with statistically significant improvements in cognitive outcomes. Specifically, there was a notable effect on Clinical Dementia Rating Sum of Boxes (CDR-SB) (SMD = -0.07; 95% [CI]: -0.12 to -0.02; p = 0.009; I² = 0%). Additionally, Alzheimer’s Disease Assessment Scale Cognitive Subscale (ADAS Cog13) (SMD = -0.10; 95% CI: -0.15 to -0.04; p = 0.0006; I² = 0%), and Mini-Mental State Examination (MMSE) ( MD = -0.28; 95% CI: -0.52 to -0.05; p = 0.02; I² = 0%), all suggested gantenerumab over placebo. However, gantenerumab significantly increased the risk of amyloid-related imaging abnormalities, including ARIA-E risk ratio of 7.79 (95% CI: 4.29 to 14.15; p < 0.00001) and ARIA-H risk ratio of 2.25 (95% CI: 1.96 to 2.58; p < 0.00001).
Conclusions:
Gantenerumab demonstrates modest benefits in functional outcomes. Although, a substantial increase in ARIA incidence counterbalances these benefits. Further long-term trials are needed to determine optimal use benefits from gantenerumab therapy.
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