Abstract
The TRAILBLAZER-ALZ 6 study (NCT05738486) evaluated the effect of different donanemab dosing regimens on amyloid-related imaging abnormalities with edema/sulcal effusions (ARIA-E). The modified titration arm met the primary outcome and significantly reduced ARIA-E frequency compared with the standard dosing while maintaining a similar pharmacodynamic effect on amyloid reduction at 24 weeks. Primary outcome and 52-week data were previously published. Completed study results at 76 weeks are reported here. ARIA-E frequencies were 15.6 % and 24.2 % in the modified titration and standard arms, respectively. ARIA-E radiographic severity was significantly lower (p = 0.015) with modified titration than with standard dosing. Additionally, symptomatic ARIA-E frequency was lower with modified titration versus standard dosing (2.8 % vs 4.8 %). The frequency of serious adverse events was comparable between the modified titration and standard dosing arms. A more gradual titration of donanemab dosing significantly reduced ARIA-E risk versus standard dosing. CLINICALTRIALS.GOV: NCT05738486.