The FDA-approved anti-amyloid-β monoclonal antibodies for the treatment of Alzheimer's disease: a systematic review and meta-analysis of randomized controlled trials

Background Alzheimer's disease (AD) is a worldwide public health problem and is difficult to cure. Drugs aimed at slowing the progression of the disease have been developed, with the Food and Drug Administration (FDA) granting accelerated approval for aducanumab on June 21, 2021 and a new accelerated approval for lecanemab on January 22, 2023. We performed this systematic review and meta-analysis to assess the efficacy and safety of FDA-approved anti-amyloid-beta (anti-A beta) monoclonal antibodies (mabs) for the treatment of AD.Method PubMed, Embase, and Cochrane Library were systematically searched to identify relevant studies published before May 2023. Efficacy outcomes included A beta, neuroimaging, and biomarker outcomes. Safety outcomes included amyloid-related imaging abnormalities with edema or effusions (ARIA-E) and ARIA with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (ARIA-H). Review Manager 5.4 software was used to assess the data. The standard mean differences (SMDs) or odds ratio (OR) with 95% confidence interval (95% CI) were analyzed and calculated with a random effect model or a fixed effect model.Result Overall, 4471 patients from 6 randomized controlled trials (RCTs), with 2190 patients in the treatment group and 2281 patients in the placebo group meeting the inclusion criteria. FDA-approved anti-A beta mabs showed statistically significant improvements in clinical outcomes, including CDR-SB (P = 0.01), ADCS-ADL-MCI (P = 0.00003), ADCOMS (P < 0.00001), ADAS-Cog (P < 0.00001). Moreover, FDA-approved anti-A beta mabs increased cerebrospinal fluid (CSF) A beta 1-42 (P = 0.002) and plasma A beta 42/40 ratios (P = 0.0008). They also decreased CSF P-Tau (P < 0.00001), CSF T-Tau (P < 0.00001), and plasma p-tau181 (P < 0.00001). FDA-approved anti-A beta mabs perform neuroimaging changes in amyloid Positron Emission Tomography Standardized Uptake Value ratio (PET SUVr) (P < 0.00001). However, compared with placebo, FDA-approved anti-A beta mabs had higher risk of ARIA-E (P < 0.00001) and ARIA-H (P < 0001).Conclusion FDA-approved anti-A beta mabs have a role in slowing disease progression in patients with AD, at the cost of an increased probability of side effects.

Automated summary

This systematic review and meta-analysis evaluated the efficacy and safety of FDA-approved anti-A beta monoclonal antibodies for the treatment of Alzheimer's disease. The findings indicate that these drugs have significant improvements in clinical outcomes and biomarkers, but also come with an increased risk of side effects.