Neurological

Therapy with donanemab modestly reduces cognitive and functional decline in patients with early Alzheimer’s disease

Eli Lilly researchers found that donanemab therapy slightly slowed cognition and decreased functionality in patients with early-stage Alzheimer’s disease (AD). These results were published in the New England Journal of Medicine.

Patients (N = 257) with early symptomatic AD were enrolled in the randomized, double-blind phase 2 TRAILBLAZER-ALZ study at 56 locations in the United States and Canada. Patients randomized in a 1: 1 ratio received 3 doses of 700 mg, then 1,400 mg of donanemab (n = 131) or placebo (n = 126) every 4 weeks for 72 weeks.

The patients underwent florbetapir positron emission tomography (PET) and the instruments Integrated AD Rating Scale (iARDS), Mini-Mental State Examination (MMSE), AD Assessment Scale (ADAS-Cog13), AD Cooperative Study-Instrumental Activities of Daily Living Inventory (ADCS-iADL) and Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB).

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The mean age of the patients in the intervention and control groups was 75.0 and 75.4 years old, 51.9% and 51.6% were women, 93.1% and 96.0% were whites, who were baseline iARDS values 106.2 and 105.9, MMSE 23.6 and 23.7, CDR-SB 3.6 and 3.4, and the amyloid plaque scores were 107.6 and 101.1 centiloids, respectively.

At week 76 the iARDS scores changed by -6.86 in the Donanemab and -10.06 in the placebo recipients (difference 3.20; 95% CI 0.12-6.27; P = 0, 04). Compared to the placebo group, the CDR-SB scores changed by -0.36 (95% CI, -0.83 to 0.12), ADAS-Cog13 by -1.86 (95% CI, -3.63 to 0.09), ADCS-iADL by 1.21 (95%) CI, -0.77 to 3.20, and MMSE by 0.64 (95% CI, -0.40 to 1.67) in the intervention cohort.

During the PET scan, florbetapir was -84.13 centiloids in the donanemab and 0.93 centiloids in the control recipients. At weeks 28 and 56, 27.4% and 54.7% of patients who received donanemab, respectively, had sufficient reductions in amyloid plaque levels to justify switching to a placebo infusion.

At least 1 side effect was reported by 90.8% of the intervention and 90.4% of the placebo groups. Amyloid-associated imaging abnormalities with edema or effusion were more common in the intervention cohort (26.7% vs. 0.8%). Antidrug antibodies were detected in 90% of Donanemab recipients.

This study was limited by drug dosage heterogeneity, as many patients were given a reduced dose due to changes in amyloid plaques.

The study authors concluded that donanemab slightly reduced cognitive and functional decline in patients with symptomatic early AD. Long term results have yet to be clarified.

Disclosure: Several authors stated links to industry. For a full list of the details, see the original article.

reference

Mintun MA, Lo AC, Evans CD, et al. Donanemab in early Alzheimer’s disease. N Engl J Med. Published online May 6, 2021. doi: 10.1056 / NEJMoa2100708

This article originally appeared on Psychiatry Advisor

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