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Hand-in-Hand: Walking Patients Through Their Journey with a Therapy for Early Alzheimer’s Disease (AD)

Chapter 1: Identifying Patients in the Mild Cognitive Impairment and Mild Dementia Stages of Alzheimer’s Disease
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  • INDICATION AND IMPORTANT SAFETY INFORMATION

    INDICATION
    LEQEMBI® (lecanemab-irmb) 100 mg/mL injection for intravenous use 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 amyloid beta, 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 asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, rarely can occur. Serious intracerebral hemorrhages >1 cm, some fatal, have been observed with this class of medications. 
      • Apolipoprotein E ε4 (ApoE ε4) Homozygotes: Patients who are ApoE ε4 homozygotes (~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. 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
    LEQEMBI is contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of the excipients of LEQEMBI. Reactions have included angioedema and anaphylaxis.

    WARNINGS AND PRECAUTIONS
    AMYLOID-RELATED IMAGING ABNORMALITIES
    ARIA-E and ARIA-H can occur together. ARIA-E can be observed on MRI as brain edema or sulcal effusions and ARIA-H as microhemorrhage and superficial siderosis. ARIA can occur spontaneously in patients with AD. ARIA-H generally occurs in association 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.

    ApoE ε4 Carrier Status and Risk of ARIA
    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 ~1% of heterozygotes and noncarriers. The recommendations on management of ARIA do not differ between ApoE ε4 carriers and noncarriers.

    Radiographic Findings
    Most ARIA-E radiographic events occurred within the first 7 doses, although ARIA can occur at any time, and patients can have >1 episode. Maximum radiographic severity of ARIA-E with LEQEMBI was mild in 4%, moderate in 7%, and severe in 1% of patients. Resolution of ARIA-E on MRI occurred in 52% of 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%).

    Intracerebral Hemorrhage
    Intracerebral hemorrhage >1 cm in diameter was reported in 0.7% LEQEMBI vs 0.1% placebo. Fatal events of intracerebral hemorrhage in patients taking LEQEMBI have been reported. 

    Concomitant Antithrombotic Medication and Other Risk Factors for Intracerebral Hemorrhage: 
    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 intracerebral hemorrhage: 0.9% LEQEMBI with a concomitant antithrombotic medication vs 0.6% no antithrombotic; 2.5% LEQEMBI with an anticoagulant alone or with antiplatelet medication/aspirin vs none receiving placebo.

    Patients were excluded from Clarity AD if neuroimaging indicated increased risk for intracerebral hemorrhage including cerebral amyloid angiopathy (prior cerebral hemorrhage >1 cm in greatest diameter, >4 microhemorrhages, superficial siderosis, vasogenic edema) or other lesions (aneurysm, vascular malformation). The presence of an ApoE ε4 allele is also associated with cerebral amyloid angiopathy. 

    Caution should be exercised when considering the administration of anticoagulants or a thrombolytic agent (e.g., tissue plasminogen activator) to a patient already being treated with LEQEMBI and in patients with factors that indicate an increased risk for intracerebral hemorrhage.

    ARIA Monitoring and Dose Management Guidelines
    Obtain a recent baseline brain MRI prior to initiating treatment with LEQEMBI and prior to the 5th, 7th, and 14th infusions. 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.

    In the event of an IRR, 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 ≥5% with LEQEMBI and ≥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%). 

    Please see full Prescribing Information for LEQEMBI, including Boxed WARNING. 

  • Sponsored by

  • Overview

    In this six-part video, Dr Gregory Cooper shares his practical perspectives and insights to help healthcare providers feel more confident identifying appropriate Alzheimer’s disease patients for the treatment option LEQEMBI®, navigating protocols for treatment and monitoring, and simplifying the patient journey. Dr Cooper is a behavioral neurologist at the Memory Center at Norton Neuroscience Institute in Louisville, Kentucky. 

    LEQEMBI® is a registered trademark of Eisai R&D Management Co., Ltd.
    © 2024 Eisai Inc. and Biogen. All trademarks are property of their respective owners.
    LEQE-US3516 06/2024 

Details
Chapters
Related
  • INDICATION AND IMPORTANT SAFETY INFORMATION

    INDICATION
    LEQEMBI® (lecanemab-irmb) 100 mg/mL injection for intravenous use 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 amyloid beta, 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 asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, rarely can occur. Serious intracerebral hemorrhages >1 cm, some fatal, have been observed with this class of medications. 
      • Apolipoprotein E ε4 (ApoE ε4) Homozygotes: Patients who are ApoE ε4 homozygotes (~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. 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
    LEQEMBI is contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of the excipients of LEQEMBI. Reactions have included angioedema and anaphylaxis.

    WARNINGS AND PRECAUTIONS
    AMYLOID-RELATED IMAGING ABNORMALITIES
    ARIA-E and ARIA-H can occur together. ARIA-E can be observed on MRI as brain edema or sulcal effusions and ARIA-H as microhemorrhage and superficial siderosis. ARIA can occur spontaneously in patients with AD. ARIA-H generally occurs in association 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.

    ApoE ε4 Carrier Status and Risk of ARIA
    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 ~1% of heterozygotes and noncarriers. The recommendations on management of ARIA do not differ between ApoE ε4 carriers and noncarriers.

    Radiographic Findings
    Most ARIA-E radiographic events occurred within the first 7 doses, although ARIA can occur at any time, and patients can have >1 episode. Maximum radiographic severity of ARIA-E with LEQEMBI was mild in 4%, moderate in 7%, and severe in 1% of patients. Resolution of ARIA-E on MRI occurred in 52% of 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%).

    Intracerebral Hemorrhage
    Intracerebral hemorrhage >1 cm in diameter was reported in 0.7% LEQEMBI vs 0.1% placebo. Fatal events of intracerebral hemorrhage in patients taking LEQEMBI have been reported. 

    Concomitant Antithrombotic Medication and Other Risk Factors for Intracerebral Hemorrhage: 
    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 intracerebral hemorrhage: 0.9% LEQEMBI with a concomitant antithrombotic medication vs 0.6% no antithrombotic; 2.5% LEQEMBI with an anticoagulant alone or with antiplatelet medication/aspirin vs none receiving placebo.

    Patients were excluded from Clarity AD if neuroimaging indicated increased risk for intracerebral hemorrhage including cerebral amyloid angiopathy (prior cerebral hemorrhage >1 cm in greatest diameter, >4 microhemorrhages, superficial siderosis, vasogenic edema) or other lesions (aneurysm, vascular malformation). The presence of an ApoE ε4 allele is also associated with cerebral amyloid angiopathy. 

    Caution should be exercised when considering the administration of anticoagulants or a thrombolytic agent (e.g., tissue plasminogen activator) to a patient already being treated with LEQEMBI and in patients with factors that indicate an increased risk for intracerebral hemorrhage.

    ARIA Monitoring and Dose Management Guidelines
    Obtain a recent baseline brain MRI prior to initiating treatment with LEQEMBI and prior to the 5th, 7th, and 14th infusions. 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.

    In the event of an IRR, 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 ≥5% with LEQEMBI and ≥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%). 

    Please see full Prescribing Information for LEQEMBI, including Boxed WARNING. 

  • Sponsored by

  • Overview

    In this six-part video, Dr Gregory Cooper shares his practical perspectives and insights to help healthcare providers feel more confident identifying appropriate Alzheimer’s disease patients for the treatment option LEQEMBI®, navigating protocols for treatment and monitoring, and simplifying the patient journey. Dr Cooper is a behavioral neurologist at the Memory Center at Norton Neuroscience Institute in Louisville, Kentucky. 

    LEQEMBI® is a registered trademark of Eisai R&D Management Co., Ltd.
    © 2024 Eisai Inc. and Biogen. All trademarks are property of their respective owners.
    LEQE-US3516 06/2024 

Schedule2 Dec 2024