Were 3 doses of Kisunla (donanemab-azbt) medically necessary for a patient with Alzheimer's disease who had a history of stroke?

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

Primary Determination

The three doses of Kisunla administered on 1/16/25,2/13/25, and 3/13/25 were NOT medically necessary because the patient had a documented stroke within 12 months prior to treatment initiation (May 19,2024), which is an explicit exclusion criterion in the Aetna Clinical Policy Bulletin 1066.

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Critical Exclusion Criterion Not Met

Recent Stroke History

• The patient suffered a stroke on May 19,2024, with documented acute cortical infarcts in the left parietal and frontal cortex, right-sided weakness, facial drooping, and disorientation 1, 2
• The first Kisunla infusion occurred on January 16,2025—only 8 months after the stroke event
• Aetna CPB 1066 explicitly excludes members with "history of transient ischemic attacks (TIA), stroke, uncontrolled hypertension, or seizures within the past 12 months" 1, 2
• This exclusion exists due to safety concerns regarding amyloid-related imaging abnormalities (ARIA), which occurred in 24% of donanemab-treated patients in clinical trials, with cerebral edema or effusions being the primary concern 2, 3

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Additional Criteria Deficiencies

Dosing Protocol Violations

• The ordered dosing regimen (700 mg for the first three doses) does NOT match FDA-approved labeling or clinical trial protocols 2, 3
• FDA-approved dosing per Aetna CPB 1066: Infusion 1 should be 350 mg, Infusion 2 should be 700 mg, and Infusion 3 should be 1,050 mg 1, 2
• The TRAILBLAZER-ALZ 2 trial protocol specified 700 mg for the first three doses, then 1400 mg thereafter, but this was the research protocol, not the FDA-approved commercial dosing 2, 3
• The provider ordered 700 mg for all three initial doses, which represents neither the FDA-approved escalation schedule nor proper adherence to established protocols

Missing Required Documentation

• No evidence of ApoE ε4 genotype testing was provided, which is required by Aetna CPB 1066 criterion G to inform patients of ARIA risk 1, 2
• No documentation of participation in a provider-enrolled patient registry (e.g., ALZ-NET) as required by criterion J 1
• MRI results prior to the 2nd and 3rd infusions (required before infusions 2,3,4, and 7) were not provided in the documentation 2, 3
• Only one MRI from 1/16/25 was documented, which showed "hemorrhagic focus/or amyloid imaging related abnormality," raising additional safety concerns

Cognitive Assessment Ambiguities

• While the patient had an MMSE score of 27/30 (meeting criterion D for scores 21-30), this score is at the high end of the range and questions whether the patient truly has the degree of cognitive impairment warranting this aggressive therapy 4
• No CDR-GS or MoCA scores were documented to corroborate the severity assessment
• The clinical notes describe "short term memory loss" and "repeating himself frequently," but objective evidence of progressive functional decline on instrumental ADLs is not clearly documented 2, 3

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Safety Concerns Specific to This Patient

Stroke History and ARIA Risk

• Patients with recent cerebrovascular events face elevated risk of ARIA-related complications 2, 3
• The baseline MRI from 1/16/25 already noted a "hemorrhagic focus/or amyloid imaging related abnormality," suggesting pre-existing vascular fragility
• In the TRAILBLAZER-ALZ 2 trial, ARIA-edema/effusion occurred in 24% of donanemab patients (52 symptomatic cases), and 3 deaths in the treatment group were considered treatment-related 2

Antiplatelet Therapy

• The patient is on aspirin 81 mg daily, which is permitted as monotherapy, but combined with recent stroke history and pre-existing hemorrhagic changes, this increases bleeding risk with donanemab 2, 3

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CPT Code 96413 Review

CPT code 96413 (Chemotherapy administration, intravenous infusion technique) is NOT appropriate for donanemab administration 1, 2

• Donanemab is an amyloid β-directed monoclonal antibody, not a chemotherapeutic agent 1, 2
• The appropriate coding for monoclonal antibody infusions would typically fall under therapeutic/diagnostic infusion codes, not chemotherapy administration
• This represents incorrect coding that could constitute billing fraud if intentional

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Evidence Quality Assessment

Donanemab Efficacy Data

• The TRAILBLAZER-ALZ 2 trial (2023) showed statistically significant but modest clinical benefits: iADRS difference of 3.25 points (95% CI 1.88-4.62) and CDR-SB difference of -0.67 points (95% CI -0.95 to -0.40) at 76 weeks in the low/medium tau population 2
• These benefits are statistically significant but of questionable clinical importance, similar to the modest effects seen with cholinesterase inhibitors (5-15% improvement over placebo) 5
• The patient is already on donepezil 10 mg and memantine, which represent standard-of-care treatments with established safety profiles 4, 6

Comparison to Established Therapies

• Cholinesterase inhibitors like donepezil show statistically significant but not clinically important improvements in ADAS-cog scores (average change not reaching the 4-point threshold for clinical significance) 5
• Donanemab's benefit profile is comparable in magnitude to these established agents but carries substantially higher risks and costs 2, 3

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Clinical Reasoning

The fundamental issue is that this patient was treated outside the safety parameters established by both the FDA approval criteria and the insurance policy's medical necessity requirements. The 12-month stroke exclusion exists because:

1. Cerebrovascular disease increases baseline ARIA risk
2. Recent stroke indicates active vascular instability
3. The patient's MRI already showed hemorrhagic changes
4. Clinical trial populations specifically excluded such patients to ensure safety data validity 2, 3

Even if all other criteria were perfectly met, the recent stroke history alone disqualifies this patient from receiving donanemab under current evidence-based guidelines.

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Common Pitfalls in Donanemab Use

• Treating patients with recent cerebrovascular events despite explicit exclusion criteria, as occurred in this case 2
• Inadequate monitoring with serial MRIs before each infusion to detect ARIA early 2, 3
• Failure to obtain ApoE ε4 genotyping to stratify ARIA risk (homozygotes have substantially higher risk) 2
• Using incorrect dosing protocols that deviate from FDA-approved labeling 1, 2
• Misclassifying the infusion as chemotherapy for billing purposes 1

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Recommendation for This Case

Retroactive denial of coverage is appropriate for all three infusions (1/16/25,2/13/25,3/13/25) based on:

1. Failure to meet exclusion criterion (stroke within 12 months)
2. Incorrect dosing protocol
3. Missing required documentation (ApoE ε4 testing, registry participation, serial MRIs)
4. Incorrect CPT coding (96413)

The patient should discontinue donanemab immediately and continue with standard-of-care therapy (donepezil and memantine), which have established safety profiles and do not carry the stroke-related contraindications 4, 6.