A recent study published in the The Journal of Prevention of Alzheimer’s Disease provides detailed insight into clinicians’ and patients’ initial experience with lecanemab, the first Food and Drug Administration-approved antiamyloid monoclonal antibody infusion proven to slow cognitive and functional decline due to Alzheimer’s disease.

Conducted at the Norton Neuroscience Institute Memory Center, the study focused on the first 71 patients treated with lecanemab, a novel disease-modifying therapy used to treat either mild cognitive impairment or mild dementia due to Alzheimer’s disease. Based on the collective experience gained, a number of useful recommendations were described to assist other centers interested in offering these novel therapies and to share real-world clinical practice experience as demand for these therapies grows.

Some lessons learned include:

• Administering prophylactic acetaminophen, loratadine and famotidine prior to lecanemab infusions appeared to be very effective at reducing the likelihood of initial infusion reactions commonly seen during initial dosing.
• We recommend a 3-tesla MRI prior to a patient’s first lecanemab infusion, given the increased sensitivity to important findings that may predict risk of side effects.
• A thorough medication review is essential prior to treatment to ensure that patients are not on any contraindicated medications.
• A support group for patients on lecanemab has provided valuable insight into the patient experience.
• A dedicated nurse navigator is an invaluable resource, given the intense logistic requirements necessary to implement these therapies.

“Our study and analysis provides valuable insight on how best to deliver these novel, groundbreaking therapies in a safe and effective manner. The experience we have gained can assist others on how to best implement anti-amyloid therapies in various health care settings across the country and internationally. Given our significant experience to date with these therapies, other organizations now seek our guidance and expertise to assist with starting their own programs,” said Kenneth Gregory Pugh, M.D., geriatric medicine specialist with the Norton Neuroscience Institute Memory Center.

Dr. Pugh was lead author of the “Initial Experience With Lecanemab and Lessons Learned in 71 Patients in a Regional Medical Center” study, published in the December 2024 issue of The Journal of Prevention of Alzheimer’s Disease.

The Food and Drug Administration approved the anti-amyloid monoclonal antibody lecanemab, sold under the brand name Leqembi, in July 2023 for individuals with mild cognitive impairment or mild dementia due to Alzheimer’s disease. The approval came after a Phase 3 clinical trial showed biweekly infusions of the drug slowed disease progression by an average of 26% at 18 months.

The medication is used to reduce the buildup of amyloid plaques in the brain. Such plaques are thought to be the initial event that drives further brain changes seen in Alzheimer’s disease.

Anticipating the FDA’s approval, Norton Neuroscience Institute had an early infrastructure in place to begin treatments as soon as possible upon regulatory approval.

The Memory Center created a multidisciplinary planning team more than six months prior to the first lecanemab infusion to create protocols to monitor safety and track imaging procedures and regulatory reporting requirements. Weekly clinical conferences review patients who have been treated with lecanemab and patients who have yet to start lecanemab infusions to ensure appropriateness of initiating or continuing treatment, as well as and safety monitoring.

A nurse navigator oversees several details of the treatment protocol and is available to give timely advice to patients and their families. The nurse navigator monitors patient compliance with the 18-month course of treatment. The Memory Center team is active in educating other physicians who may be less familiar with these treatments, including neurologists, emergency department physicians, radiologists and intensive care specialists who might be involved in treating patients on lecanemab.

Participants in the six-month study were chosen from among 1,249 patients evaluated for potential eligibility.

The 71 chosen were diagnosed with mild cognitive impairment or mild dementia due to Alzheimer’s disease, which was confirmed mostly through cerebrospinal fluid biomarkers for Alzheimer’s disease pathology. They were treated at the multidisciplinary Memory Center from August 2023 to March 2024. All participants received at least one infusion of lecanemab.

Dealing with infusion reactions

Twenty-six patients (37%) experienced infusion reactions after their first lecanemab infusion. Headaches (12 patients) and shaking/chills/rigors (11 patients) were most common. Twenty-three (88%) of these 26 patients reported the side effects either at the infusion center or within the first 24 hours after infusion.

Amyloid-related imaging abnormalities (ARIA)

In the study, imaging showed ARIA in 12 of the 50 study participants (24%) who completed one or more safety monitoring MRIs following lecanemab infusions. Three-quarters of the cases of ARIA were completely asymptomatic. This is similar to findings observed in the initial clinical trials leading to lecanemab’s approval by the FDA.

Patients in the study were more likely to have ARIA if they were homozygous for the APOE4 genotype, as expected, given the increased risk associated with carrying two copies of APOE 4. Of the nine patients homozygous for the APOE4 genotype, four (44%) had evidence of ARIA. Among the 36 patients who were heterozygous, 17% were diagnosed with ARIA. No patients experienced any permanent or serious side effects due to ARIA.

Private insurance and Medicare coverage

Medicare does not require authorization, and patients are routinely scheduled for infusions without difficulty. Medicare Advantage plans have been more difficult, requiring appeal letters and peer-to-peer reviews. Individual insurers have unique requirements for assessing eligibility and may require specific testing. Unfortunately, some private insurance companies are denying coverage for lecanemab treatment.

Health care system lessons learned

The study also offered lessons learned from the perspective of a health care organization.

The study recommended giving medical bracelets to lecanemab patients, to identify them and manage them in the emergency department, and having their charts flagged in the electronic medical record system. In cases of a lecanemab patient complaining of symptoms that might represent ARIA, knowledge of their treatment helps prevent inappropriate CT scans looking for brain bleeding or swelling. Lecanemab patients require a brain MRI to assess for potential ARIA, if concerning symptoms arise.

Other organizational recommendations included standardizing radiology reports to assess initial candidacy for therapy, monitor safety and assess severity of ARIA. Expanding the number of infusion sites to reduce the distances some patients need to travel is a future goal for the treatment team. Since publication, the Memory Center is also participating in an important national registry, ALZ-NET, to document ongoing collective experience globally with these novel therapies.