Resources that are downloadable and printable for easy access
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Screenings & Diagnosis
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Initiate & Manage Treatment
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Videos
Screenings & Diagnosis
PCP Checklist
A convenient resource for primary care providers (PCPs) that helps with identifying symptoms, screening, and referring appropriate patients who are candidates for LEQEMBI
LEQEMBI® Diagnostic Workup Checklist
A checklist intended to help health care professionals determine the appropriateness of LEQEMBI therapy and document clinical decision-making
Confirming Amyloid Beta (Aβ) Flashcard
An overview of the various ways to confirm amyloid beta via positron emission tomography (PET), cerebrospinal fluid (CSF) analysis, or blood-based biomarkers (BBMs)
Assessment Tools for Early and Ongoing Detection Flashcard
A streamlined resource for helping you identify symptoms of AD early and through the long term
The Role of BBMs in Early Detection of AD Pathology
A guide that details why BBMs matter, their use in a triage or confirmatory manner, and available testing assays
Initiate & Manage Treatment
Diagnosis to Treatment Brochure
Brochure that provides an overview of the steps involved from diagnosis through treatment with LEQEMBI (for eligible patients)
Assess and Monitor ARIA Risk Flashcard
A quick guide to help you manage amyloid-related imaging abnormalities (ARIA) in your patients
Specialty Distributors and Specialty Pharmacy Network Guide
Specialty Distributors and Specialty Pharmacy Network Guide
List of the specialty distributors and the specialty pharmacy that stock LEQEMBI
LEQEMBI Wallet Card
A wallet card to help patients inform health care professionals that they are taking LEQEMBI
My LEQEMBI Appointment Tracker
Encourage patients and care partners to use the LEQEMBI appointment tracker to help them stay on top of their treatment schedule
Videos
Mechanism of AD
What is the mechanism of action of LEQEMBI
5 facts about the Clinical Dementia Rating-Sum of Boxes (CDR-SB) in MCI due to AD
How to use LEQEMBI® IQLIK™
Mechanism of AD
Transcript
The amyloid cascade is an ongoing, bidirectional process that contributes to progressive neurodegeneration in Alzheimer's disease or AD.
It is known to trigger downstream effects such as tau pathology, increased oxidative stress, and inflammation.
The cascade begins with increased amyloid beta production and decreased clearance, causing amyloid to build up in the brain.
This results in larger amyloid beta aggregates, which can interfere with brain cell communication and can lead to neurodegeneration.
Monomers, dimers, oligomers, and protofibrils are soluble amyloid beta species whose accumulation leads to the formation of insoluble fibrils and amyloid plaques. This process is called the amyloid cascade model.
Oligomers affect brain cell structure and functioning.
Protofibrils directly damage neurons, impair brain cell signaling, and are hypothesized to be the most toxic amyloid beta aggregate.
Fibrils and amyloid plaques are linked to impaired brain cell signaling and are found in areas of brain cell death.
Amyloid beta accumulation due to the amyloid cascade begins decades before clinical symptoms of AD become apparent.
Proactive confirmation of amyloid beta accumulation may aid in the diagnosis of mild cognitive impairment due to AD and mild AD dementia.
Mechanism of AD
What is the mechanism of action of LEQEMBI?
Transcript
SUMMARY OF IMPORTANT SAFETY INFORMATION
INDICATION
LEQEMBI® is indicated for the treatment of Alzheimer's disease. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.
SUMMARY OF MOST SERIOUS AND MOST COMMON RISKS ASSOCIATED WITH LEQEMBI
BOXED WARNING: AMYLOID-RELATED IMAGING ABNORMALITIES (ARIA)
CONTRAINDICATION: Contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of the excipients. Reactions have included angioedema and anaphylaxis.
WARNINGS AND PRECAUTIONS: ARIA; HYPERSENSITIVITY REACTIONS; INFUSION-RELATED REACTIONS
MOST COMMON ADVERSE REACTIONS: infusion-related reactions, ARIA-H, ARIA-E, headache, superficial siderosis of central nervous system, rash, and nausea/vomiting.
Injection-site reactions have occurred with LEQEMBI IQLIK.
Please see full Important Safety Information below and accompanying full US Prescribing Information, including Boxed WARNING.
Alzheimer's disease is a devastating chronic, progressive disease which results in the decline of both cognitive abilities and daily functioning.
It is caused by the degeneration and death of brain cells critical for processing, storing, and retrieving information. One key hallmark of the disease is the abnormal accumulation of a protein called amyloid beta, which results from an imbalance of its production and clearance. Amyloid beta builds up in 2 forms, known as aggregated soluble and insoluble proteins.
Mild cognitive impairment is the first symptomatic stage of the disease where memory and cognitive functions begin to be impaired but not severe enough to significantly disrupt daily life.
LEQEMBI is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody and the first fully approved FDA treatment that works on fighting Alzheimer's disease in 2 ways. First, LEQEMBI targets and clears insoluble amyloid beta plaques that have been accumulating for years. Second, LEQEMBI works to clear toxic, soluble aggregates of amyloid beta proteins such as oligomers and protofibrils.
LEQEMBI is an early Alzheimer's disease treatment designed to selectively target toxic protofibrils in addition to amyloid plaques. As a result of LEQEMBI binding to these toxic forms of the amyloid beta, it enables the microglia, the brain's immune cells, to recognize the toxic proteins and clear them out of the body via phagocytosis.
Early detection of abnormal amyloid accumulation via biomarker analysis, in addition to clinical symptoms, is critical in the diagnosis of patients with mild cognitive impairment due to Alzheimer's disease who may be appropriate for LEQEMBI.
INDICATION
LEQEMBI® is indicated for the treatment of Alzheimer's disease (AD). Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment (MCI) or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.
IMPORTANT SAFETY INFORMATION
WARNING: AMYLOID-RELATED IMAGING ABNORMALITIES (ARIA)
Monoclonal antibodies directed against aggregated forms of beta amyloid, including LEQEMBI, can cause ARIA, characterized as ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H). Incidence and timing of ARIA vary among treatments. ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, can occur. ARIA can be fatal. Serious intracerebral hemorrhages (ICH) greater than 1 cm, some of which have been fatal, have been observed with this class of medications. Because ARIA-E can cause focal neurologic deficits that can mimic an ischemic stroke, consider whether such symptoms could be due to ARIA-E before giving thrombolytic therapy to a patient being treated with LEQEMBI.
Apolipoprotein E ε4, (ApoE ε4) Homozygotes: Patients who are ApoE ε4 homozygotes (approximately 15% of patients with AD) treated with this class of medications have a higher incidence of ARIA, including symptomatic, serious, and severe radiographic ARIA, compared to heterozygotes and noncarriers. Testing for ApoE ε4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA. Prior to testing, prescribers should discuss with patients the risk of ARIA across genotypes and the implications of genetic testing results. Prescribers should inform patients that if genotype testing is not performed, they can still be treated with LEQEMBI; however, it cannot be determined if they are ApoE ε4 homozygotes and at higher risk for ARIA.
Consider the benefit of LEQEMBI for the treatment of AD and the potential risk of serious ARIA events when deciding to initiate treatment with LEQEMBI.
CONTRAINDICATION
Contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of the excipients. Reactions have included angioedema and anaphylaxis.
WARNINGS AND PRECAUTIONS
AMYLOID-RELATED IMAGING ABNORMALITIES
Medications in this class, including LEQEMBI, can cause ARIA-E, which can be observed on MRI as brain edema or sulcal effusions, and ARIA-H, which includes microhemorrhage and superficial siderosis. ARIA can occur spontaneously in patients with AD, particularly in patients with MRI findings suggestive of cerebral amyloid angiopathy (CAA), such as pretreatment microhemorrhage or superficial siderosis. ARIA-H generally occurs with ARIA-E. Reported ARIA symptoms may include headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms usually resolve over time.
Incidence of ARIA
Symptomatic ARIA occurred in 3% and serious ARIA symptoms in 0.7% with LEQEMBI. Clinical ARIA symptoms resolved in 79% of patients during the period of observation. ARIA, including asymptomatic radiographic events, was observed: LEQEMBI, 21%; placebo, 9%. ARIA-E was observed: LEQEMBI, 13%; placebo, 2%. ARIA-H was observed: LEQEMBI, 17%; placebo, 9%. No increase in isolated ARIA-H was observed for LEQEMBI vs placebo.
Incidence of ICH
ICH greater than 1 cm in diameter was reported in 0.7% with LEQEMBI vs 0.1% with placebo. Fatal events of ICH in patients taking LEQEMBI have been observed.
Risk Factors of ARIA and ICH
ApoE ε4 Carrier Status
Of the patients taking LEQEMBI, 16% were ApoE ε4 homozygotes, 53% were heterozygotes, and 31% were noncarriers. With LEQEMBI, ARIA was higher in ApoE ε4 homozygotes (LEQEMBI: 45%; placebo: 22%) than in heterozygotes (LEQEMBI: 19%; placebo: 9%) and noncarriers (LEQEMBI: 13%; placebo: 4%). Symptomatic ARIA-E occurred in 9% of ApoE ε4 homozygotes vs 2% of heterozygotes and 1% of noncarriers. Serious ARIA events occurred in 3% of ApoE ε4 homozygotes and in approximately 1% of heterozygotes and noncarriers. The recommendations on management of ARIA do not differ between ApoE ε4 carriers and noncarriers.
Radiographic Findings of CAA
Neuroimaging findings that may indicate CAA include evidence of prior ICH, cerebral microhemorrhage, and cortical superficial siderosis. CAA has an increased risk for ICH. The presence of an ApoE ε4 allele is also associated with CAA.
The baseline presence of at least 2 microhemorrhages or the presence of at least 1 area of superficial siderosis on MRI, which may be suggestive of CAA, have been identified as risk factors for ARIA. Patients were excluded from Clarity AD for the presence of greater than 4 microhemorrhages and additional findings suggestive of CAA (prior cerebral hemorrhage greater than 1 cm in greatest diameter, superficial siderosis, vasogenic edema) or other lesions (aneurysm, vascular malformation) that could potentially increase the risk of ICH.
Concomitant Antithrombotic or Thrombolytic Medication
In Clarity AD, baseline use of antithrombotic medication (aspirin, other antiplatelets, or anticoagulants) was allowed if the patient was on a stable dose. Most exposures were to aspirin. Antithrombotic medications did not increase the risk of ARIA with LEQEMBI. The incidence of ICH: 0.9% in patients taking LEQEMBI with a concomitant antithrombotic medication vs 0.6% with no antithrombotic and 2.5% in patients taking LEQEMBI with an anticoagulant alone or with antiplatelet medication such as aspirin vs none in patients receiving placebo.
Fatal cerebral hemorrhage has occurred in 1 patient taking an anti-amyloid monoclonal antibody in the setting of focal neurologic symptoms of ARIA and the use of a thrombolytic agent.
Additional caution should be exercised when considering the administration of antithrombotics or a thrombolytic agent (for example, tissue plasminogen activator) to a patient already being treated with LEQEMBI. Because ARIA-E can cause focal neurologic deficits that can mimic an ischemic stroke, treating clinicians should consider whether such symptoms could be due to ARIA-E before giving thrombolytic therapy in a patient being treated with LEQEMBI.
Caution should be exercised when considering the use of LEQEMBI in patients with factors that indicate an increased risk for ICH and, in particular, patients who need to be on anticoagulant therapy or patients with findings on MRI that are suggestive of CAA.
Radiographic Severity With LEQEMBI
Most ARIA-E radiographic events occurred within the first 7 doses, although ARIA can occur at any time and patients can have greater than 1 episode. Maximum radiographic severity of ARIA-E with LEQEMBI was mild in 4%, moderate in 7%, and severe in 1% of patients. Resolution on MRI occurred in 52% of ARIA-E patients by 12 weeks, 81% by 17 weeks, and 100% overall after detection. Maximum radiographic severity of ARIA-H microhemorrhage with LEQEMBI was mild in 9%, moderate in 2%, and severe in 3% of patients; superficial siderosis was mild in 4%, moderate in 1%, and severe in 0.4% of patients. With LEQEMBI, the rate of severe radiographic ARIA-E was highest in ApoE ε4 homozygotes (5%) vs heterozygotes (0.4%) or noncarriers (0%). With LEQEMBI, the rate of severe radiographic ARIA-H was highest in ApoE ε4 homozygotes (13.5%) vs heterozygotes (2.1%) or noncarriers (1.1%).
Monitoring and Dose Management Guidelines
Baseline brain MRI and periodic monitoring with MRI are recommended. Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment. Depending on ARIA-E and ARIA-H clinical symptoms and radiographic severity, use clinical judgment when considering whether to continue dosing or to temporarily or permanently discontinue LEQEMBI. If a patient experiences ARIA symptoms, clinical evaluation should be performed, including MRI if indicated. If ARIA is observed on MRI, careful clinical evaluation should be performed prior to continuing treatment.
HYPERSENSITIVITY REACTIONS
Hypersensitivity reactions, including angioedema, bronchospasm, and anaphylaxis, have occurred with LEQEMBI. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction and initiate appropriate therapy.
INFUSION-RELATED REACTIONS (IRRs)
IRRs were observed—LEQEMBI: 26%; placebo: 7%—and most cases with LEQEMBI (75%) occurred with the first infusion. IRRs were mostly mild (69%) or moderate (28%). Symptoms included fever and flu-like symptoms (chills, generalized aches, feeling shaky, and joint pain), nausea, vomiting, hypotension, hypertension, and oxygen desaturation.
IRRs can occur during or after the completion of infusion. In the event of an IRR during the infusion, the infusion rate may be reduced or discontinued, and appropriate therapy initiated as clinically indicated. Consider prophylactic treatment prior to future infusions with antihistamines, acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids.
ADVERSE REACTIONS
The most common adverse reactions reported in greater than or equal to 5% with LEQEMBI infusion every 2 weeks and greater than or equal to 2% higher than placebo were IRRs (LEQEMBI: 26%; placebo: 7%), ARIA-H (LEQEMBI: 14%; placebo: 8%), ARIA-E (LEQEMBI: 13%; placebo: 2%), headache (LEQEMBI: 11%; placebo: 8%), superficial siderosis of central nervous system (LEQEMBI: 6%; placebo: 3%), rash (LEQEMBI: 6%; placebo: 4%), and nausea/vomiting (LEQEMBI: 6%; placebo: 4%)
Safety profile of LEQEMBI IQLIK for maintenance treatment was similar to LEQEMBI infusion. Patients who received LEQEMBI IQLIK experienced localized and systemic (less frequent) injection-related reactions (mild to moderate in severity)
LEQEMBI (lecanemab-irmb) is available:
Intravenous infusion: 100 mg/mL
Subcutaneous injection: 200 mg/mL
What is the mechanism of action of LEQEMBI?
LEQEMBI works to remove 2 forms of amyloid: 1) Insoluble plaque—the final aggregated form of Aβ that accumulates over years; 2) Soluble protofibrils—direct toxic drivers of underlying disease that are continuously produced even after plaque clearance.1-3
5 facts about the Clinical Dementia Rating-Sum of Boxes (CDR-SB) in MCI due to AD
Transcript
The Clinical Dementia Rating Sum of Boxes, or CDR-SB, is a highly sensitive research tool that can be used to detect changes in a patient's condition that are meaningful, both clinically and to patients and care partners. It has been used as an endpoint in clinical trials of early Alzheimer's disease.
I'm Doctor Joy Snider, and I'm going to share the 5 top facts to know about this measure so we can better evaluate the results of these trials, regardless of whether you utilize the CDR-SB in clinical practice. Let's get started.
Fact one: The CDR-SB is valid, reliable, and sensitive in the early AD population.
AD can be divided into 5 stages. Preclinical AD, where there is evidence of AD pathology in the brain without any clinical symptoms. Mild cognitive impairment or MCI. Mild AD dementia. Moderate AD dementia and severe AD dementia. It should be noted that MCI can be associated with a number of causes such as sleep disorders, medication, depression, and other neurological disorders. Here, we are specifically referring to MCI due to AD. The earlier AD is identified and treated, the greater the opportunity for benefit. Therefore, recent clinical studies have focused on the earliest symptomatic stage of AD: MCI due to AD in the mild AD dementia stage. Because of this, there has been interest in tools that can track disease progression in early AD and clinical trials. As we said earlier, the CDR-SB has been shown to be a valid, reliable, and sensitive tool in this population, making it widely used in clinical research.
Fact 2: The CDR-SB is a measure of disease severity and is the sum of the scores across 6 domains of the CDR.
Initially developed here at Washington University School of Medicine in Saint Louis, Missouri, is a staging tool to categorize dementia severity. The Clinical Dementia Rating, or CDR, is a scale used to characterize 6 domains applicable to AD. The domains assess cognitive and functional performance. It is administered as a structured interview with both the patient and a reliable informant, such as a family member.
The CDR yields 2 scores. The global CDR, which stages disease on a scale from 0 to 3, and the CDR-SB, which is a more granular measure of disease severity and is the sum of the scores across the 6 domains.
Each domain is scored on a scale of impairment ranging from 0 to 3, with 0 being normal level of function and higher scores indicating greater impairment. The total score for the CDR-SB can range from 0 to 18. However, in early AD the typical ranges from 0.5 to 6.
This brings us to fact 3: Compared with the global CDR, the CDR-SB is more sensitive to smaller increments of change.
The use of CDR-SB scores for staging disease severity offers several advantages over the global score because the increased granularity of CDR-SB makes the assessment helpful for tracking changes across time. Furthermore, it is sensitive to smaller increments of change in a patient's cognition. Importantly, progression on an individual domain of the CDR-SB can be a meaningful change for a patient.
In early AD, natural disease progression within 18 months is 1.5 to 2 points on the CDR-SB. In fact, this is our fourth fact.
For example, let's look at the memory, orientation, and judgment and problem-solving domains.
The CDR-SB is highly sensitive and can detect changes in a patient's condition that are meaningful, both clinically and to patients and care partners.
With respect to memory, a shift of just 0.5 points on the CDR scoring table, such as progressing from 0.5 to 1, could indicate a decline from consistent, slight forgetfulness to forgetfulness that interferes with everyday activities. In my experience, patients with a score of 0.5 still remember events well, like going out to eat with friends the day before or where they went on vacation a few weeks ago.
Patients with a score of 1 are more likely to forget the pertinent details of recent events. A shift from .5 to 1 also could mean a patient who had been able to manage their own appointments may now need reminders.
With respect to the orientation domain score, at 0.5, the patient can still be driving and going places with only slight difficulty understanding time relationships. And a score of 1, driving might have to be limited to familiar areas. This could mean a change from being able to drive to visit family in a distant city to limiting driving to just their local neighborhood.
And as patients move from .5 to 1 in the judgment and problem-solving domain, they go from having mild difficulty solving problems and detecting similarities and differences, to moderate difficulty. This could meet a need for more support from a care partner to negotiate daily life. For example, a score of 0.5 indicates that patients may still manage their finances and balance their checkbook, but it might take a little longer. They may still plan a trip and book their own travel, but with a score of 1, patients will need help with these tasks.
Okay, we've made it to fact 5. The CDR-SB has been widely used in clinical trials in early AD.
This is because, as noted earlier, the CDR-SB has been shown to be a valid, reliable, and sensitive tool in the early AD population. It is also considered a clinically meaningful endpoint by the US Food and Drug Administration.
To wrap up, here are the top 5 facts to know about the use of the CDR-SB in evaluating early AD. Hopefully, this overview aids understanding of the sensitivity of the CDR-SB and its meaningfulness, both clinically as well as to patients and care partners. Please share this with your team members and colleagues to help them interpret the results of early AD clinical trials.
5 facts about the Clinical Dementia Rating-Sum of Boxes (CDR-SB) in MCI due to AD
The primary endpoint in the Phase 3 Clarity AD study was change from baseline in CDR-SB.1 This video highlights 5 key takeaways to help understand its clinical meaningfulness and importance to the mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) population.
How to use LEQEMBI® IQLIK™
Transcript
This video will teach you how to use LEQEMBI® IQLIK™.
This once-weekly, at-home maintenance treatment is an available option to patients after 18 months of LEQEMBI infusions.
LEQEMBI is a prescription medicine used to treat people with Alzheimer's disease, which includes mild cognitive impairment (MCI) or mild dementia stage of disease.
Before you start using LEQEMBI IQLIK, read the Instructions for Use and the Medication Guide that you received with your autoinjector.
You should also read them each time you refill because there may be new information. This information does not take the place of talking to your health care provider about your medical condition or your treatment. If you have any questions about how to use the autoinjector, contact your health care provider.
Meet Sophia, she'll be demonstrating the injection process.
This is Sophia's husband, Rick. He's here to help.
Place your supplies on a clean, flat surface.
You'll need the LEQEMBI IQLIK autoinjector, cotton ball or gauze, an adhesive bandage, an alcohol wipe, and a sharps disposal container.
Your LEQEMBI IQLIK arrives in a refrigerated carton.
When you are ready to inject, take one out and let it sit at room temperature for 20 minutes.
Check the carton and autoinjector for damaged or broken seals.
Do not use if the expiration date on the carton has passed, or if the perforations on the carton are broken.
Check the viewing window. Do not use the autoinjector if it has been damaged or dropped, looks cloudy, discolored, or contains particles. The liquid should be clear and colorless to pale yellow. Air bubbles are normal.
Do not use if the expiration date has passed.
Once at room temperature, it can stay out for up to 14 days, but don't put it back in the fridge.
Use 1 injector weekly as directed.
Before you inject, wash your hands with soap and water, or use hand sanitizer.
Do not inject through clothing.
You can inject into the front of the thighs or stomach area.
If a care partner helps, they can also inject in the back of the upper arms.
Do not inject into moles, scars, bruises, tattoos, or red or injured skin. Do not inject into the 2-inch area around your belly button or through clothing.
Pick your site at least 1 inch away from your last injection.
Clean with an alcohol wipe and let it air dry.
Don't touch, fan, or blow after it's been cleaned.
Remove the clear cap by pulling it straight off. Don't twist or bend.
Throw the cap away in your trash or sharps container.
Place the magenta needle cover flat against the skin at a 90-degree angle.
Push down firmly to start the injection. Hold steady.
You may hear a click, which means the injection has started.
The purple plunger rod will move down in the viewing window during the injection.
If you have trouble hearing the click, watch the purple plunger rod as it moves down.
Hold for about 10 seconds.
You'll then hear a second click, which means the injection is complete. Keep holding for 5 more seconds.
Pull the autoinjector straight up. The magenta needle cover will automatically move into place to cover the needle.
You may notice a small drop of blood. This is normal. Press a cotton ball or gauze on the area and cover with a bandage if needed. Do not rub the injection site.
Throw away the used injector into a sharps container.
If you don't have an FDA-cleared sharps container, use a heavy-duty plastic container with a tight-fitting, puncture-resistant lid. Label it clearly.
When it's almost full, follow local guidelines to dispose of it properly.
That's it.
We've covered how to gather your supplies and prepare, inject, and dispose of LEQEMBI IQLIK.
You can watch this video again any time.
If you have questions, reach out to your health care provider.
Scan the QR code to download a wallet card that informs your health care provider you are taking LEQEMBI IQLIK.
INDICATION
LEQEMBI® is indicated for the treatment of Alzheimer's disease (AD). Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment (MCI) or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.
IMPORTANT SAFETY INFORMATION
WARNING: AMYLOID-RELATED IMAGING ABNORMALITIES (ARIA)
Monoclonal antibodies directed against aggregated forms of beta amyloid, including LEQEMBI, can cause ARIA, characterized as ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H). Incidence and timing of ARIA vary among treatments. ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, can occur. ARIA can be fatal. Serious intracerebral hemorrhages (ICH) greater than 1 cm, some of which have been fatal, have been observed with this class of medications. Because ARIA-E can cause focal neurologic deficits that can mimic an ischemic stroke, consider whether such symptoms could be due to ARIA-E before giving thrombolytic therapy to a patient being treated with LEQEMBI.
Apolipoprotein E ε4 (ApoE ε4) Homozygotes: Patients who are ApoE ε4 homozygotes (approximately 15% of patients with AD) treated with this class of medications have a higher incidence of ARIA, including symptomatic, serious, and severe radiographic ARIA, compared to heterozygotes and noncarriers. Testing for ApoE ε4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA. Prior to testing, prescribers should discuss with patients the risk of ARIA across genotypes and the implications of genetic testing results. Prescribers should inform patients that if genotype testing is not performed, they can still be treated with LEQEMBI; however, it cannot be determined if they are ApoE ε4 homozygotes and at higher risk for ARIA.
Consider the benefit of LEQEMBI for the treatment of AD and the potential risk of serious ARIA events when deciding to initiate treatment with LEQEMBI.
CONTRAINDICATION
Contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of the excipients. Reactions have included angioedema and anaphylaxis.
WARNINGS AND PRECAUTIONS
AMYLOID-RELATED IMAGING ABNORMALITIES
Medications in this class, including LEQEMBI, can cause ARIA-E, which can be observed on MRI as brain edema or sulcal effusions, and ARIA-H, which includes microhemorrhage and superficial siderosis. ARIA can occur spontaneously in patients with AD, particularly in patients with MRI findings suggestive of cerebral amyloid angiopathy (CAA), such as pretreatment microhemorrhage or superficial siderosis. ARIA-H generally occurs with ARIA-E. Reported ARIA symptoms may include headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms usually resolve over time.
Incidence of ARIA
Symptomatic ARIA occurred in 3% and serious ARIA symptoms in 0.7% with LEQEMBI. Clinical ARIA symptoms resolved in 79% of patients during the period of observation. ARIA, including asymptomatic radiographic events, was observed: LEQEMBI, 21%; placebo, 9%. ARIA-E was observed: LEQEMBI, 13%; placebo, 2%. ARIA-H was observed: LEQEMBI, 17%; placebo, 9%. No increase in isolated ARIA-H was observed for LEQEMBI vs placebo.
Incidence of ICH
ICH greater than 1 cm in diameter was reported in 0.7% with LEQEMBI vs 0.1% with placebo. Fatal events of ICH in patients taking LEQEMBI have been observed.
Risk Factors of ARIA and ICH
ApoE ε4 Carrier Status
Of the patients taking LEQEMBI, 16% were ApoE ε4 homozygotes, 53% were heterozygotes, and 31% were noncarriers. With LEQEMBI, ARIA was higher in ApoE ε4 homozygotes (LEQEMBI: 45%; placebo: 22%) than in heterozygotes (LEQEMBI: 19%; placebo: 9%) and noncarriers (LEQEMBI: 13%; placebo: 4%). Symptomatic ARIA-E occurred in 9% of ApoE ε4 homozygotes vs 2% of heterozygotes and 1% of noncarriers. Serious ARIA events occurred in 3% of ApoE ε4 homozygotes and in approximately 1% of heterozygotes and noncarriers. The recommendations on management of ARIA do not differ between ApoE ε4 carriers and noncarriers.
Radiographic Findings of CAA
Neuroimaging findings that may indicate CAA include evidence of prior ICH, cerebral microhemorrhage, and cortical superficial siderosis. CAA has an increased risk for ICH. The presence of an ApoE ε4 allele is also associated with CAA.
The baseline presence of at least 2 microhemorrhages or the presence of at least 1 area of superficial siderosis on MRI, which may be suggestive of CAA, have been identified as risk factors for ARIA. Patients were excluded from Clarity AD for the presence of greater than 4 microhemorrhages and additional findings suggestive of CAA (prior cerebral hemorrhage greater than 1 cm in greatest diameter, superficial siderosis, vasogenic edema) or other lesions (aneurysm, vascular malformation) that could potentially increase the risk of ICH.
Concomitant Antithrombotic or Thrombolytic Medication
In Clarity AD, baseline use of antithrombotic medication (aspirin, other antiplatelets, or anticoagulants) was allowed if the patient was on a stable dose. Most exposures were to aspirin. Antithrombotic medications did not increase the risk of ARIA with LEQEMBI. The incidence of ICH: 0.9% in patients taking LEQEMBI with a concomitant antithrombotic medication vs 0.6% with no antithrombotic and 2.5% in patients taking LEQEMBI with an anticoagulant alone or with antiplatelet medication such as aspirin vs none in patients receiving placebo.
Fatal cerebral hemorrhage has occurred in 1 patient taking an anti-amyloid monoclonal antibody in the setting of focal neurologic symptoms of ARIA and the use of a thrombolytic agent.
Additional caution should be exercised when considering the administration of antithrombotics or a thrombolytic agent (for example, tissue plasminogen activator) to a patient already being treated with LEQEMBI. Because ARIA-E can cause focal neurologic deficits that can mimic an ischemic stroke, treating clinicians should consider whether such symptoms could be due to ARIA-E before giving thrombolytic therapy in a patient being treated with LEQEMBI.
Caution should be exercised when considering the use of LEQEMBI in patients with factors that indicate an increased risk for ICH and, in particular, patients who need to be on anticoagulant therapy or patients with findings on MRI that are suggestive of CAA.
Radiographic Severity With LEQEMBI
Most ARIA-E radiographic events occurred within the first 7 doses, although ARIA can occur at any time and patients can have greater than 1 episode. Maximum radiographic severity of ARIA-E with LEQEMBI was mild in 4%, moderate in 7%, and severe in 1% of patients. Resolution on MRI occurred in 52% of ARIA-E patients by 12 weeks, 81% by 17 weeks, and 100% overall after detection. Maximum radiographic severity of ARIA-H microhemorrhage with LEQEMBI was mild in 9%, moderate in 2%, and severe in 3% of patients; superficial siderosis was mild in 4%, moderate in 1%, and severe in 0.4% of patients. With LEQEMBI, the rate of severe radiographic ARIA-E was highest in ApoE ε4 homozygotes (5%) vs heterozygotes (0.4%) or noncarriers (0%). With LEQEMBI, the rate of severe radiographic ARIA-H was highest in ApoE ε4 homozygotes (13.5%) vs heterozygotes (2.1%) or noncarriers (1.1%).
Monitoring and Dose Management Guidelines
Baseline brain MRI and periodic monitoring with MRI are recommended. Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment. Depending on ARIA-E and ARIA-H clinical symptoms and radiographic severity, use clinical judgment when considering whether to continue dosing or to temporarily or permanently discontinue LEQEMBI. If a patient experiences ARIA symptoms, clinical evaluation should be performed, including MRI if indicated. If ARIA is observed on MRI, careful clinical evaluation should be performed prior to continuing treatment.
HYPERSENSITIVITY REACTIONS
Hypersensitivity reactions, including angioedema, bronchospasm, and anaphylaxis, have occurred with LEQEMBI. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction and initiate appropriate therapy.
INFUSION-RELATED REACTIONS (IRRs)
IRRs were observed—LEQEMBI: 26%; placebo: 7%—and most cases with LEQEMBI (75%) occurred with the first infusion. IRRs were mostly mild (69%) or moderate (28%). Symptoms included fever and flu-like symptoms (chills, generalized aches, feeling shaky, and joint pain), nausea, vomiting, hypotension, hypertension, and oxygen desaturation.
IRRs can occur during or after the completion of infusion. In the event of an IRR during the infusion, the infusion rate may be reduced or discontinued, and appropriate therapy initiated as clinically indicated. Consider prophylactic treatment prior to future infusions with antihistamines, acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids.
ADVERSE REACTIONS
The most common adverse reactions reported in greater than or equal to 5% with LEQEMBI infusion every 2 weeks and greater than or equal to 2% higher than placebo were IRRs (LEQEMBI: 26%; placebo: 7%), ARIA-H (LEQEMBI: 14%; placebo: 8%), ARIA-E (LEQEMBI: 13%; placebo: 2%), headache (LEQEMBI: 11%; placebo: 8%), superficial siderosis of central nervous system (LEQEMBI: 6%; placebo: 3%), rash (LEQEMBI: 6%; placebo: 4%), and nausea/vomiting (LEQEMBI: 6%; placebo: 4%)
Safety profile of LEQEMBI IQLIK for maintenance treatment was similar to LEQEMBI infusion. Patients who received LEQEMBI IQLIK experienced localized and systemic (less frequent) injection-related reactions (mild to moderate in severity)
LEQEMBI (lecanemab-irmb) is available:
Intravenous infusion: 100 mg/mL
Subcutaneous injection: 200 mg/mL
How to use LEQEMBI® IQLIK™
Is your patient starting LEQEMBI at-home subcutaneous injections? Share this video to help guide them on how to use LEQEMBI IQLIK safely and correctly.