Public Health.

Area of Science:

• Neurology
• Pharmacology
• Clinical Trials

Background:

• Alzheimer's disease treatments, including anti-amyloid monoclonal antibodies like lecanemab and donanemab, show varying safety profiles.
• Understanding these differences is crucial for patient care and treatment selection.

Purpose of the Study:

• To conduct an indirect treatment comparison (ITC) of lecanemab and donanemab.
• To evaluate and compare safety outcomes, specifically ARIA (amyloid-related imaging abnormalities) and death, between these two anti-amyloid therapies.

Main Methods:

• An indirect treatment comparison (ITC) utilizing ARIA rates from FDA labels, review documents, and publications.
• Compared lecanemab and donanemab using placebo as a common comparator, analyzing ARIA-E, ARIA-H, intracerebral hemorrhage (ICH), and death over 18 months.
• Employed anchored Bucher ITCs and risk difference-in-difference (RDD) analysis to assess treatment effects.

Main Results:

• Lecanemab demonstrated significantly lower risks of any ARIA (ARIA-E or ARIA-H) compared to donanemab (RDD: -10.1%).
• Significant reductions in ARIA-E (-10.7%) and ARIA-H (-10.1%) were observed with lecanemab, persisting in APOE4 carriers.
• Lecanemab showed lower risks of microhemorrhage and superficial siderosis; ICH and all-cause death were not significantly different, but lecanemab had a lower risk of death with concurrent ARIA or ICH.

Conclusions:

• Lecanemab exhibits significantly lower risks of ARIA outcomes compared to donanemab, including deaths associated with ARIA or ICH.
• These findings highlight distinct safety profiles between the two anti-amyloid therapies.
• Further real-world studies are needed to inform clinical decision-making regarding comparative safety.