Review questions clinical benefit of anti-amyloid Alzheimer's drugs as PET study probes ARIA-E
A review of 17 studies involving 20,342 patients found anti-amyloid Alzheimer’s drugs had “trivial” effects after 18 months and increased the risk of brain swelling and bleeding. A separate PET study suggested ARIA-E may mark brain regions with greater amyloid plaque reduction.
A new review found that anti-amyloid medicines for Alzheimer’s disease made “no meaningful difference to patients” while increasing the risk of swelling and bleeding in the brain. Separate new PET findings suggested that amyloid-related imaging abnormality edema (ARIA-E), a known side effect of treatments such as lecanemab and donanemab, may indicate that certain parts of the brain are more responsive to treatment.
The new Cochrane review looked at 17 studies involving 20,342 patients overall. Most had either mild cognitive impairment, dementia, or both, with a mean age of 70 to 74. The studies included trials on anti-amyloid drugs lecanemab and donanemab, as well as aducanumab, which has been discontinued by its manufacturer, and bapineuzumab, crenezumab and solanezumab, which were discontinued after failed trials.
The analysis found that the effects of these drugs on cognitive function and dementia severity after 18 months was “trivial.” The effects of the medicines on those with early-stage Alzheimer’s and dementia were “either absent or consistently small,” and the differences made by the treatments were “far below the minimal effect that’s needed to be noticeable at all for patients and caregivers.” The evidence suggested that while early trials showed results that were statistically significant, there was no clinically meaningful effect.
The drugs could also increase the risk of swelling and bleeding in the brain, according to the review. These side effects were seen in brain scans and caused no symptoms for most patients, although the long-term impact was unclear. The review also noted that most studies reported after 18 months, a “relatively short” window “in the context of a slowly progressive condition like Alzheimer’s,” while in clinical practice these drugs may likely be used for much more than 18 months.
ARIA-E is a known side effect of anti-amyloid monoclonal antibody treatments, such as lecanemab and donanemab. Though the condition typically resolves on its own, in rare cases the side effects associated with the drugs, such as seizures, coma and brain hemorrhage, can be deadly. Routine brain imaging is recommended for patients to monitor for signs of ARIA-E.
In the PET study, researchers analyzed the cases of a handful of patients with ARIA-E. Using PET scans, the team quantified changes in Aβ PET signal before and after ARIA-E resolution, comparing regions affected by ARIA-E with unaffected regions. Areas of the brain that swelled the most tended to show the greatest reduction of plaques after the swelling resolved, suggesting certain areas might be more responsive to treatment than others.
More research is needed to validate the PET findings, as the study sample size was quite small. The team plans to expand on the work with additional institutions, including the Longitudinal Early Onset Alzheimer’s Disease Study consortium.
The review comes after it emerged that Nice is looking again at evidence on donanemab and lecanemab following successful appeals by their manufacturers Eli Lilly and Eisai.