Efficacy and Safety of Donanemab in the Treatment of Alzheimer's Disease: A Systematic Review and Meta-Analysis

Introduction: Donanemab is a monoclonal antibody targeting amyloid-β plaques. This study aims to quantify donanemab’s consistent cognitive benefits, biomarker efficacy, and safety risks by pooling data from all available RCTs. Materials and Methods: Systematic searches were conducted in PubMed, the Cochrane Library, Web of Science, and Embase. Phase II/III randomized controlled trials comparing donanemab with placebo in amyloid-positive early Alzheimer’s disease were included. After screening 133 records, two trials met the inclusion criteria. Results: Donanemab significantly reduced cognitive decline (iADRS +2.93; 95% CI: 1.52– 4.33; P < 0.0001) and functional progression (CDR-SB -0.66; 95% CI: -0.90 to -0.42; P < 0.00001), with amplified benefits in low/medium tau burden patients (iADRS +3.80; 95% CI: 2.10– 5.50). Amyloid clearance was dramatically higher with donanemab (risk ratio (RR) = 234.46; 95% CI: 68.17–806.38; P < 0.00001), with 76.4% achieving amyloid-negative status. There were significantly elevated risks of ARIA-E (RR = 12.90; 95% CI: 8.15–20.43; P < 0.00001), ARIA-H (RR = 2.86; 95% CI: 1.61–5.06; P = 0.0003), and treatment discontinuation (RR = 3.26; 95% CI: 2.38– 4.47; P < 0.00001), whereas all-cause mortality was not significantly different (RR = 1.44; 95% CI: 0.69–3.00). Discussion: Donanemab showed statistically significant cognitive benefits, but its clinical meaningfulness warrants careful interpretation. The iADRS improvement of 2.93 points and the CDRSB reduction in all patients of 0.66 points did not approach their minimal clinically important difference (MCID). Conclusion: Donanemab provides statistically significant but modest benefits in early AD, particularly in low-tau subgroups. However, the magnitude of cognitive and functional improvement did not approach the threshold for a MCID in the overall population, which requires stringent safety monitoring for ARIA. Clinical implementation should prioritize PET stratification and APOEguided surveillance.