Amyloid-related imaging abnormalities seen in about 40% of aducanumab users in clinical trials

Reuters Health - 25/11/2021 - Amyloid-related imaging abnormalities (ARIA) occurred in about 40% of adults with early Alzheimer's disease (AD) who participated in the phase-3 studies of the anti-amyloid agent aducanumab (Aduhelm, Biogen), with about one-quarter of these patients experiencing symptoms, according to a secondary safety analysis.

"With the recent U.S. FDA approval of aducanumab, the EMERGE and ENGAGE trials provide a large safety data set for characterizing ARIA and informing real-world practice," corresponding author Dr. Karen Smirnakis of Biogen told Reuters Health by email.

This analysis shows that ARIA in the two phase-3 trials of aducanumab were "mostly mild or moderate in nature, occurred early in the course of treatment, were often self-resolving and clinically manageable. Serious ARIA events occurred, but were uncommon," Dr. Smirnakis said.

Among the 3,285 participants in the two trials, 425 of 1,029 (41%) patients taking 10 mg/kg aducanumab experienced ARIA, she and her colleagues report in JAMA Neurology.

ARIA-edema occurred in 362 patients (35%), and 94 of these patients (26%) experienced associated symptoms including headache, confusion, dizziness and nausea. The incidence of ARIA-E with aducanumab was highest in carriers of the APOE e4 allele. Most events among those with ARIA-E resolved radiographically.

ARIA-microhemorrhage and ARIA-superficial siderosis occurred in 197 patients (19.1%) and 151 patients (14.7%), respectively.

"Although ARIA can occur at any time, clinical suspicion for ARIA should be highest in early treatment, and routine surveillance MRIs should be supplemented with ad hoc MRIs in patients with new-onset symptoms potentially associated with ARIA," the authors note in their paper.

"In patients with identified ARIA, prescribers should carefully assess the radiographic and clinical findings when deciding whether to continue dosing," they advise.

"Safety data collected while treating patients with aducanumab in real-world settings as well as clinical settings through the phase 3b EMBARK redosing trial and forthcoming FDA-mandated confirmatory clinical studies will continue to inform best practices and characterization of ARIA in the clinic," they say.

The FDA granted accelerated approval of aducanumab in June against the advice of its own expert advisory committee.

SOURCE https://bit.ly/3xa9YUO JAMA Neurology, online November 22, 2021.

By Megan Brooks



Posted on 25 November, 20218 December, 2021