Were 3 doses of Kisunla (donanemab-azbt) medically necessary for a patient with Alzheimer's disease, who had a history of stroke and received 700mg doses, deviating from the recommended dosing schedule?

Medical Necessity Review: Donanemab (Kisunla) for Alzheimer's Disease

Direct Answer

The three doses of Kisunla were NOT medically necessary for this patient, and the claim should be denied based on multiple critical exclusion criteria and protocol deviations. 1

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Primary Exclusion Criterion: Recent Stroke History

This patient had a documented stroke in [DATE], which is within 12 months of treatment initiation, making them ineligible for donanemab therapy. 1

• Patients with cerebrovascular events within the past 12 months face substantially elevated risk of amyloid-related imaging abnormalities (ARIA), including life-threatening cerebral edema and hemorrhage 1
• The American College of Cardiology and guideline societies explicitly exclude patients with recent stroke from donanemab treatment due to these safety concerns 1
• This exclusion criterion exists because the risk-benefit ratio becomes unacceptable in patients with compromised cerebrovascular integrity 1

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Critical Dosing Protocol Violations

The provider administered 700 mg for all three initial doses, which directly contradicts FDA-approved dosing and represents a significant safety concern. 1

FDA-Approved Dosing Schedule:

• Infusion 1: 350 mg 1
• Infusion 2: 700 mg 1
• Infusion 3: 1,050 mg 1

What Was Actually Given:

• Infusions 1-3: 700 mg each (incorrect) 1

This deviation from FDA-approved labeling is a common pitfall in donanemab use and compromises both safety and efficacy. 1 The escalating dose protocol exists to minimize ARIA risk while achieving therapeutic amyloid clearance 2, 3. Administering higher-than-approved doses initially (700 mg vs. 350 mg) increases the risk of serious adverse events, particularly ARIA-related complications 3.

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Missing Required Safety Monitoring

Multiple essential safety requirements were not documented, further supporting denial:

ApoE ε4 Genotyping Not Provided:

• Failure to obtain ApoE ε4 genotyping prior to treatment is a critical safety oversight 1
• This testing is mandatory to stratify ARIA risk, as ApoE ε4 carriers have substantially higher rates of cerebral edema and hemorrhage 3
• Without this information, informed consent regarding individualized risk cannot be properly obtained 1

Serial MRI Monitoring Not Documented:

• MRI results prior to the 2nd and 3rd infusions were not provided 1
• Serial MRIs before each infusion are required to detect ARIA early and prevent serious complications 1
• The single MRI from [DATE] showing "hemorrhagic focus/or amyloid imaging related abnormality" raises additional safety concerns that should have triggered enhanced monitoring 1

Registry Participation Not Confirmed:

• No documentation that the patient or provider is participating in a required patient registry (e.g., ALZ-NET) 1
• Registry participation is mandated to collect real-world safety and efficacy data 1

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Incorrect CPT Coding

CPT code 96413 (chemotherapy administration) is inappropriate for donanemab infusion. 1

• Donanemab is a monoclonal antibody, not chemotherapy 4, 3
• The appropriate coding would fall under therapeutic/diagnostic infusion codes, not chemotherapy administration 1
• Using incorrect CPT coding for billing purposes is a common pitfall in donanemab use and suggests inadequate understanding of the medication 1

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Clinical Context and Alternative Treatment

Even if this patient had been eligible, the modest benefits of donanemab must be weighed against substantial risks and costs:

Efficacy Data:

• The TRAILBLAZER-ALZ 2 trial showed statistically significant but clinically modest benefits: iADRS difference of 3.25 points and CDR-SB difference of -0.67 points at 76 weeks 1, 3
• The strength of evidence for donanemab's efficacy is moderate at best 1
• Some experts argue that marginal cognitive improvements do not justify the risks and costs 5

Safety Profile:

• ARIA-edema occurred in 24% of patients (52 symptomatic) in clinical trials 3
• Three deaths in the donanemab group were considered treatment-related 3
• Infusion-related reactions occurred in 8.7% of patients 3

Standard-of-Care Alternatives:

• This patient is already receiving appropriate standard therapy with donepezil and memantine 6, 7
• Donepezil is the first-line medication for Alzheimer's disease with established efficacy and a favorable safety profile 6, 7
• The patient's MMSE score of 27/30 indicates relatively preserved cognition, suggesting current therapy may be adequate 8, 6

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Summary of Denial Rationale

Medical necessity cannot be established due to:

1. Absolute contraindication: Stroke within 12 months of treatment initiation 1
2. Dosing protocol violations: Incorrect doses administered for first three infusions 1
3. Missing safety requirements: No ApoE ε4 genotyping, incomplete MRI monitoring, no registry participation 1
4. Incorrect billing codes: Use of chemotherapy administration code for monoclonal antibody infusion 1
5. Unfavorable risk-benefit ratio: Modest efficacy gains do not justify substantial ARIA risks in a patient with cerebrovascular disease 1, 3

The patient should continue evidence-based standard therapy with cholinesterase inhibitors and memantine, which provide comparable benefits with substantially lower risks and costs. 6, 7