Korean J Clin Pharm.  2023 Dec;33(4):290-304. 10.24304/kjcp.2023.33.4.290.

Systemic Literature Review Study on the Efficacy and Safety of Novel Alzheimer’s Disease Treatments

• Park S
• Chang H
• Sohn H
• Shim M

• KMID: 2553209
• DOI: http://doi.org/10.24304/kjcp.2023.33.4.290

Abstract

Background
Innovative Alzheimer’s disease drugs received approval in the United States in 2021 and 2023. This study aims to assess the safety and efficacy of these novel treatments, elucidate their mechanisms of action, and compare their impact on cognitive function improvement with approved drugs.
Methods
We conducted a comprehensive search of pivotal clinical studies related to Alzheimer’s disease treatments in PubMed/Medline, Embase, and the Cochrane Library databases from January 1st, 2020 to December 31st, 2022. Meta-analysis was performed using RevMan 5.4 software.
Results
A total of 14 studies were included in this systematic review. When compared to the placebo, the new drugs did not exhibit a statistically significant effect on MMSE (MiniMental State Examination) (mean difference= −0.04, 95% confidence intervals [CIs]: −0.31, 0.23, N=3662, I² =0%). However, they demonstrated a significant impact on ADAS-cog (Alzheimer’s Disease Assessment Scale-Cognitive Subscale) (standardized mean difference= −0.15, 95% CIs: −0.2, −0.1, N=6710, I² =17%). When compared to the approved drugs, the new drugs showed a statistically significantly lower effect on MMSE (test for subgroup difference Chi² =23.13, N = 5870, p<0.00001) but showed only a trend of decreased efficacy on ADAS-cog (Chi² =1.16, N = 8670, p=0.28).
Conclusion
New drugs yielded diverse clinical endpoint results compared to the placebo, and in comparison to existing approved drugs, they exhibited lower efficacy in improving cognitive function. The safety profile of these new drugs, as reported in clinical trials, was generally well-tolerated.

Keyword

Aducanumab; alzheimer disease; alzheimer’s disease assessment scale-cognitive subscale (ADAS-Cog); lecanemab; mini-mental state examination (MMSE); systematic review