Sequential Lecanemab→Donanemab Therapy in Alzheimer’s Disease: Real-World PET Findings
Abstract:
Anti-amyloid monoclonal antibodies such as lecanemab and donanemab have shown robust amyloid clearance and modest clinical benefit in Alzheimer’s disease. Japan’s staggered regulatory approvals of these agents provided a unique opportunity for sequential therapy. To evaluate real-world amyloid PET evidence of sequential lecanem ab→donanemab therapy compared with lecanemab monotherapy and untreated controls. Thirty-one individuals who underwent amyloid PET between 2019 and 2025 were retrospectively analyzed. Participants were classified into sequential therapy (n = 16), lecanemab monotherapy (n = 5), and untreated controls (n = 14). Global and regional standardized uptake value ratios were calculated and converted into Centiloid units. Statistical compar isons were performed using Wilcoxon signed-rank and Welch’s t-tests with Cohen’s d. Significant amyloid reduc tions were observed in both treated groups, with greater decreases in sequential therapy group (−70.6 Centiloids) than in lecanemab monotherapy (−48.4). Sequential therapy induced significant reductions across all cortical regions, particularly in the precuneus (p = 0.034, d = 0.95). Cognitive scores remained stable in sequential therapy group but declined in controls. No amyloid-related imaging abnormalities were detected. Sequential lecanem ab→donanemab therapy achieved stronger and regionally distinct amyloid reductions than monotherapy, without safety concerns. This real-world evidence suggests that sequential antibody use may extend the biological effects of anti-amyloid therapy in Alzheimer’s disease. Prospective trials are warranted to confirm clinical efficacy and optimize treatment sequencing.
