Doctors warn against off-label use of new Alzheimer's drug for cerebral amyloid angiopathy

According to the International Cerebral Amyloid Angiography Association, there is no evidence that monoclonal antibody aducanumab is a beneficial treatment for patients with cerebral amyloid angiopathy.BOSTON - A new therapy for Alzheimer's disease that was approved by the U.S. Food and Drug Administration should not be prescribed to patients off-label by doctors for cerebral amyloid angiopathy. This cerebrovascular condition is similar to Alzheimer's, says Steven Greenberg, MD, PhD. Greenberg is the director of the Hemorrhagic stroke Research Program at Massachusetts General Hospital (MGH), and president of International Cerebral Amyloid Angiopathy Association. Greenberg, along with eight other members of the association, wrote in a letter published by The Lancet Neurology that there was no evidence that monoclonal antibody aducanumab has any benefit for patients suffering from CAA. This is a condition where proteins called amyloid corrode the arterial walls of the brain, leading to bleeding and stroke.The letter stated that "there are substantial uncertainties, concerns about both safety and efficacy [of aducanumab] in patients with CAA and] we believe [it] shouldn't be used for the purposes of treating CAA beyond the context of a clinical trial."FDA approved aducanumab in accordance with the FDA's expedited approval process for drugs that treat serious medical conditions or fill unmet medical needs. Although the FDA approved aducanumab for Alzheimer's, doctors can legally prescribe it off-label to treat cerebral amyloid angiopathy. CAA, like Alzheimer's disease, is believed to be caused by the accumulation of harmful amyloid beta brain deposits. However, unlike Alzheimer's, these deposits are found in brain tissue and not the cerebral blood vessels. The FDA gave the green light for aducanumab. This was contrary to the FDA's independent advisory committee and many doctors, scientists, and other medical professionals who claim there is no evidence that the drug can help patients.Leading experts in cerebral amyloid angiopathy are now advocating that aducanumab be not prescribed off-label to treat CAA. The ICAAA officers commented that amyloid beta plaques in brain blood vessels are more resistant to anti-inflammatory treatment than plaque deposits in brain tissue. There was also insufficient evidence to support the claim that aducanumab could clear those blood vessels. Physicians cited a clinical trial of ponezumab (an anti-amyloid antibody), which showed that patients with CAA had worsened rather than improved blood vessel function after three monthly infusions.Greenberg and his colleagues addressed safety concerns by citing the fact that patients who had been enrolled in anti-amyloid antibody drug trials of aducanumab or other anti-amyloid antibodies drugs were experiencing major adverse reactions. CAA is believed to trigger ARIAs. These are bleeding and swelling of the brain that can be detected by MRI imaging. Worrisome for physicians was the possibility that abnormalities could occur more often in patients with CAA than in patients with Alzheimer's disease.Greenberg disapproved of off-label use for aducanumab. However, he made a distinction between cerebral amyloid angiopathy patients and those with Alzheimer's disease. He says, "We haven’t taken a stance on whether an Alzheimer’s patient with markers of CAA should also be prescribed aducanumab." "What we're saying is that the drug should not be prescribed to treat CAA.###Greenberg, a Harvard Medical School professor of Neurology, is an internationally recognized authority in the diagnosis, causes, and treatment of cerebral amyloid-angiopathy.The Massachusetts General HospitalThe original and largest Harvard Medical School teaching hospital, Massachusetts General Hospital was established in 1811. With more than 9500 researchers across 30 centers, institutes and departments, the Mass General Research Institute is the nation's largest hospital-based research program. It has an annual budget of $1 billion. Mass General was ranked #6 on the U.S. News & World Report "America's Best Hospitals" list in August 2020.