Background: Anti-amyloid monoclonal antibodies lecanemab (Leqembiâ) and donanemab (Kisunla^TM) have been approved by the U.S. Food and Drug Administration for patients with mild cognitive impairment or mild dementia due to Alzheimer’s disease.

Methods: We examined 187 patients who received at least one lecanemab infusion over a 2-year duration and 51 patients who received at least one donanemab infusion over a 1-year period at the Norton Neuroscience Institute Memory Center.  We adhered to the lecanemab and donanemab appropriate use recommendations regarding surveillance brain MRIs to monitor for ARIA.^1,2 After several infusion-related reactions were reported, we instituted a pretreatment oral cocktail of acetaminophen 650 mg, loratadine 10 mg, and famotidine 20 mg.  All patients receiving donanemab received the same pre-infusion cocktail.

Results: Of the 175 patients who underwent at least one surveillance brain MRI following lecanemab initiation, 39 (22.3%) had evidence of ARIA (both ARIA-H and ARIA-E: 13 [33.3%]; solitary ARIA-H: 17 [43.6%]; and solitary ARIA-E: 9 [23.1%]). ARIA was detected in 12 of the 25 (48.0%) e4 homozygotes, 20 of the 95 (21.0%) e4 heterozygotes, and 7 of the 55 (12.7%) e4 non-carriers.  Of the 48 patients who underwent at least one surveillance brain MRI after starting donanemab, 10 (20.8%) had ARIA detected (both ARIA-H and ARIA-E: 5 [50.0%]; solitary ARIA-H: 3 [30.0%]; and solitary ARIA-E: 2 [20.0%]). ARIA was observed in 3 of the 6 (50%) e4 homozygotes, 5 of the 17 (29.4%) e4 heterozygotes, and only 2 of the 25 (8.0%) e4 non-carriers.  Of the patients who developed ARIA, 5 treated with lecanemab were symptomatic compared to none receiving donanemab.  Of the 145 patients who were treated with lecanemab after the pre-infusion cocktail was incorporated, 41 (28.3%) had an infusion-related adverse event.  Seven (13.7%) patients treated with donanemab experienced infusion-related side effects.  Thirty-two (17.1%) patients discontinued lecanemab, primarily due to cognitive decline associated with progressive AD (10 [31.2%]) and ARIA progression (9 [28.1%]).  Eight (15.7%) patients discontinued donanemab due to ARIA progression in 5, severe infusion reactions in 2, and need for anticoagulants in 1

Conclusion: Our findings conclude that lecanemab and donanemab have a similar incidence of ARIA and both may be safely used in a real-world setting.  Rates of ARIA in real-world settings are similar to those observed in pivotal clinical trials.

References: ¹ Cummings J, Apostolova L, Rabinovici GD, Atri A, Aisen P, Greenberg S, et al. Lecanemab: appropriate use recommendations. J Prev Alzheimers Dis 2023;10:362-77.

²   Rabinovici GD, Selkoe DJ, Schindler SE, Aisen P, Apostolova LG, Atri A, et al. Donanemab: appropriate use recommendations. J Prev Alzheimers Dis 2025;12:100150.