Aducanumab Might Cause Brain Swelling in 35% of Alzheimer's disease patients: JAMA
Aduhelm (Aducanumab) becomes the first treatment approved for Alzheimer's disease in almost 20 years. However, a recent safety analysis suggests that 41.3 per cent of all trial participants experienced some kind of brain imaging abnormality throughout the study. The study findings were published in the journal JAMA Neurology on November 22, 2021.
The controversies around Aduhelm started since the early phase of approval as an independent data monitoring committee had looked at the early results and concluded the drug didn't seem to be working. Later, Biogen revealed that the findings were premature and further investigations showed positive results from patients exposed to higher doses of the drug for longer periods of time. Based on on two phase III studies, EMERGE and ENGAGE findings FDA granted approval for aduhelm.
After approval Aduhelm transverse a rocky road as FDA went ahead despite a score of specialists and senior FDA officials pointing out that it was unclear whether Aduhelm would benefit patients. Followed later by the death of a 75-year-old trial participant and Biogen responded to the report saying the causes of death remain unknown at this time. Now, several months later, the aducanumab story continues after the findings of the secondary analysis.
Dr Stephen Salloway and his team conducted a secondary analysis of data from the EMERGE and ENGAGE trials, which were 2 double-blind, placebo-controlled, parallel-group, phase 3 randomized clinical trials that compared low-dose and high-dose aducanumab treatment with placebo. They included a total of 3285 participants with Alzheimer disease who received one or more doses of placebo (n = 1087) or aducanumab (n = 2198; 2752 total person-years of exposure) during the placebo-controlled period.
The major outcome assessed was the incidence of amyloid-related imaging abnormalities (ARIA) which was monitored using brain magnetic resonance imaging. Associated symptoms were reported as adverse events.
Key Findings of the Study:
- During the placebo-controlled period, the researchers noted that 41.3% experienced ARIA, with serious cases occurring in 14 patients (1.4%).
- They also noted that ARIA-edema (ARIA-E) was the most common adverse event (35.2%), and 72.7% occurred within the first 8 doses of aducanumab; 26.0%with an event exhibited symptoms.
- They observed that most of those affected by the ARIA-edema did not report any symptoms, but among those who did, headache, confusion and dizziness were commonly experienced.
- They found that the incidence of ARIA-E was highest in aducanumab-treated participants who were apolipoprotein E ε4 allele carriers.
- They further noted that most events (98.2%) among those with ARIA-E resolved radiographically and 82.8% resolved within 16 weeks.
- In the placebo group, they observed 2.7% had ARIA-E. 19.1% had ARIA-microhemorrhage and 14.7% ARIA–superficial siderosis.
The study is one of the first formal publications of safety data to stem from the two final-stage trials of Aduhelm.
The authors concluded, "In this integrated safety data set from EMERGE and ENGAGE, the most common adverse event in the 10-mg/kg group was ARIA-E, which occurred in 362 of the 1029 patients (35.2%) in the 10-mg/kg group with at least 1 postbaseline MRI scan, with 94 patients (26.0%) experiencing associated symptoms. The most common associated symptom was headache."
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