Pennsylvania GeriatricS Society

This year’s Fall Program was designed to educate attendees on currently available therapeutic options for major neurocognitive disorder, highlighting new monoclonal antibody therapies. The risks and benefits of the use of these novel agents were highlighted through a pro-con debate style interactive learning session. Attendees walked away with the knowledge to be able to recognize currently available therapeutic options, compare risks and benefits of monoclonal antibody therapy in major neurocognitive disorder, and identify dosing and monitoring strategies for safe use of monoclonal antibody therapy in major neurocognitive disorder.

At the end of the debate, attendees voted on whether they would prescribe the case patient with lecanemab. 77% voted that they would not prescribe this drug, while 23% would prescribe lecanemab.

Whether you would prescribe lecanemab or not, here are some key takeaways from the debate –

Lecanemab Medication Highlights

• Must have mild cognitive impairment or mild dementia due to Alzheimer’s disease.
• Lecanemab is a monoclonal antibody, preferentially targets soluble aggregated amyloid beta (aβ)
• Dosing: 10 mg/kg IV infusion over 1 hour, once every 2 weeks
• Duration: Up to 18 months of treatment
• Requires close monitoring by prescriber and team and regularly scheduled MRIs.
• The Clarity AD Phase 3 trial results:
• o   Mean difference in CDR-SB score vs.   Placebo: -0.45 (95% CI: -0.67 to -0.23)
• o   27% slowing of decline after 18 months.
• What is the clinical significance of a -0.45 difference on the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB)? A 0.5-point difference in the score may mean the difference between “consistent slight forgetfulness” and “moderate memory loss: more marked for recent events; defect interferes with everyday activity.”

Safety Takeaways

• Infusion-related reactions were common (over 25%), mostly mild, and preventable with pre-medication.
• Amyloid-related imaging abnormalities (ARIA) were mostly mild to moderate in severity, occurred early, and typically resolved within 4 months.
• Symptomatic ARIA was relatively rare: 2.8% and 0.7% of lecanemab group had symptomatic ARIA-E (edema) and ARIA-H (hemorrhage), respectively.
• ARIA more common in ApoE ε4 carriers, especially homozygotes
• Discontinuation due to adverse event: 6.9% in lecanemab group vs. 2.9% in control group