Real-world evidence for amyloid-targeted therapies: Lecanemab and donanemab.

INTRODUCTION

Real-world safety data on amyloid-targeted therapies in early Alzheimer's disease remain limited, particularly for modified donanemab titration and direct lecanemab-donanemab comparisons.

METHODS

Retrospective review of 172 amyloid-positive patients treated with lecanemab (n = 89) or donanemab (original titration n = 21; modified n = 62). The cohort included patients with ≥2 chronic comorbidities (72.7%), systemic autoimmune or hematologic disorders, and concurrent immunomodulators.

RESULTS

Amyloid-related imaging abnormalities (ARIA) occurred in 11.2% (10/89) with lecanemab and 13.3% (11/83) with donanemab-less than in pivotal trials. Modified donanemab titration reduced ARIA versus the original protocol (8.1% vs 28.6%; p = 0.03) and TRAILBLAZER-ALZ 6 (23.6%). No anaphylaxis occurred. Surveillance magnetic resonance imaging captured 95.2% of ARIA events. Within-center comparison showed comparable safety between lecanemab and modified-titration donanemab (all p's > 0.40). IRRs occurred in 12.0% (donanemab) and 9.0% (lecanemab).

DISCUSSION: In a real-world cohort representing patients excluded from trials, ARIA and IRR rates matched or improved upon pivotal trials, supporting safe ATT use under FDA-approved MRI intervals.