LECANEMAB-IRMB INJ,SOLN
Clinical Criteria Summary
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Exclusion Criteria
- Age less than 60 years
- Medical, neurological, or mental health condition contributing to cognitive impairment
- Contraindication to or inability to complete brain MRI
- Transient ischemic attack, stroke, or seizures within the past year
- Evidence of other clinically significant lesions on brain MRI indicating another cause of dementia
- Screening MRI evidence excluding treatment (including >4 microhemorrhages, single macro hemorrhage >10 mm, superficial siderosis, vasogenic edema, acute/subacute cerebral contusion or stroke, aneurysms, vascular malformations, infective lesions, severe small vessel/white matter disease, space-occupying lesions, or intra-axial brain tumors)
- ApoE e4 homozygote
- Uncontrolled immunological disease or requirement for biologic drug treatment
- Untreated bleeding disorder, platelet count <50,000 x 109/L, or INR >1.5
- Thyroid stimulating hormone above normal range (TSH > 5 mU/L if < 65 years old; TSH > 7.5 mU/L if > 65 years old)
- Low serum vitamin B12 level
- Untreated human immunodeficiency virus (HIV)
- Malignant neoplasm under active therapy (unless approved by oncologist)
- Positive Columbia-Suicide Severity Rating Scale (C-SSRS) suicidal ideation item 4 or 5, or any suicidal behavior within the past 6 months
- Hospitalization or treatment for suicidal behavior in the past 5 years
- Current substance use disorder or positive urine drug screen
- Use of anti-platelet or anti-coagulant medications (e.g., apixaban, clopidogrel, NSAIDs, t-PA), except aspirin
Inclusion Criteria
- Prescriber must be a VA board-certified neurologist, geriatric psychiatrist, or geriatrician specializing in dementia treatment
- Signed informed consent on file; if genotype testing is not performed, patient and provider accept the risk
- Meets criteria for mild cognitive impairment (MCI) or mild Alzheimer’s disease (AD) dementia
- MRI scan completed within the last 6 months
- Amyloid PET imaging, cerebrospinal fluid (CSF) analysis consistent with AD (e.g., Beta-amyloid [1-42] < 1030 pg/ml), or clearly positive blood biomarker (e.g., FDA-cleared Lumipulse G pTau 217/B-Amyloid 42 Plasma Ratio >0.00738)
- Cognitive/functional assessment scores meeting thresholds: Mini-Mental State Examination (MMSE) score > 21, Saint Louis University Mental Status (SLUMS) score > 16, Montreal Cognitive Assessment (MoCA) score > 16, or Functional Assessment Staging Test (FAST) Stage 2-4
- Neuroradiology available to review serial MRI scans (at site or through National Teleradiology)
- Established process to hold infusion until ordering physician assesses patient and determines whether to continue treatment
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Indication & Disease State
- • Treatment of Alzheimer’s disease
- • Initiated in patients with mild cognitive impairment (MCI) or mild dementia stage of disease
- • Confirmed presence of Aβ pathology
Patient Selection & Inclusion Criteria
- • Diagnosis of MCI due to AD (CDR score 0.5) or mild AD (CDR score 0.5-1)
- • Memory impairment [Wechsler Memory Scale IV-Logical Memory (subscale) II] >1 standard deviation below age-adjusted mean
- • Positive biomarker for brain amyloid pathology (PET, CSF t-tau/Aβ)
- • Aged > 50 and < 90 years
- • MMSE score between 22 and 30
- • BMI > 17 and < 35
- • If using drugs to treat symptoms related to AD, doses must be stable for at least 12 weeks prior to baseline
Exclusion Criteria
- • Any neurological condition (other than AD) that may contribute to cognitive impairment
- • Transient ischemic attack, stroke, or seizures within 1 year prior to screening
- • Psychiatric diagnosis or symptoms interfering with procedures (e.g., hallucinations, major depression, delusions)
- • Geriatric Depression Scale (GDS) score ≥ 8 at screening
- • Contraindications to MRI scanning (cardiac pacemaker/defibrillator, ferromagnetic metal implants)
- • Evidence of other clinically significant lesions on brain MRI indicating a dementia diagnosis other than AD
- • Significant pathological findings on brain MRI: >4 microhemorrhages; single macro hemorrhage >10 mm; superficial siderosis; vasogenic edema; cerebral contusion, encephalomalacia, aneurysms, vascular malformations, infective lesions; multiple lacunar infarcts/stroke involving a major vascular territory, severe small vessel/white matter disease; space-occupying lesions; brain tumors
- • Immunological disease not adequately controlled or requiring biologic drugs during treatment
- • Bleeding disorder not under adequate control (platelet count <50,000 or INR >1.5)
- • Thyroid stimulating hormone above normal range
- • Abnormally low serum vitamin B12 levels
- • HIV positive status
- • Malignant neoplasms within 3 years of screening
- • Suicidal ideation Type 4 or 5 on C-SSRS, suicidal behavior within 6 months before/at screening/baseline, or hospitalization/treatment for suicidal behavior in past 5 years
- • Drug or alcohol abuse/dependence within 2 years before screening or positive urine drug test at screening
Dosing & Administration
- • Injection: 100 mg/ml
- • Intravenous (IV) infusion, 10 mg/kg, over an hour, every 2 weeks
Monitoring & Safety Management
- • Requires a recent (within one year) brain MRI prior to initiating treatment
- • Periodic MRI monitoring required prior to the 5th, 7th, and 14th infusions
- • Enhanced clinical vigilance for amyloid-related imaging abnormalities (ARIA) during the first 14 weeks of treatment
- • Mild ARIA: Continue dosing if asymptomatic; suspend dosing if symptomatic
- • Moderate to severe ARIA: Temporarily suspend dosing until resolution
- • Severe ARIA-H: Permanently discontinue dosing
- • Infusion-related reactions: Reduce or discontinue infusion rate and administer appropriate therapy as clinically indicated; consider pre-medication with antihistamine, NSAIDs, or corticosteroids at subsequent dosing