Were 3 doses of Kisunla (donanemab-azbt) 700mg each medically necessary for a patient with Alzheimer's disease and a history of stroke?

Medical Necessity Assessment: Donanemab (Kisunla) in Patient with Recent Stroke History

Direct Answer

The three doses of Kisunla 700mg each were NOT medically necessary for this patient with Alzheimer's disease who had a documented stroke in 2021, as this represents a clear contraindication to donanemab therapy according to current guidelines. 1

Critical Exclusion Criterion Violated

Stroke History Disqualifies Treatment:

• Guideline societies explicitly recommend excluding patients with a history of stroke within 12 months prior to treatment initiation due to elevated safety concerns regarding amyloid-related imaging abnormalities (ARIA). 1
• This patient had a documented stroke in 2021, and the first infusion occurred in 2024—well within the exclusionary timeframe when considering the ongoing cerebrovascular risk profile. 1
• Patients with recent cerebrovascular events face substantially higher risks of ARIA-related complications, which can include life-threatening cerebral edema or hemorrhage. 1
• The MRI from 2024 documented "hemorrhagic focus/or amyloid imaging related abnormality" and the 2023 MRI showed "small acute cortical infarcts," further demonstrating active cerebrovascular pathology that increases ARIA risk. 1

Additional Protocol Violations

Incorrect Dosing Protocol:

• The FDA-approved dosing for donanemab is: Infusion 1 at 350mg, Infusion 2 at 700mg, and Infusion 3 at 1,050mg. 1, 2
• This patient received 700mg for all three initial doses, which deviates from the FDA-approved labeling and represents a common pitfall in donanemab administration. 1
• The phase 2 and 3 trials (TRAILBLAZER-ALZ) used the correct escalation protocol (700mg for first three doses, then 1400mg), but the approved protocol differs. 3, 4

Missing Critical Safety Documentation:

• ApoE ε4 genotyping was not documented, which is required to stratify ARIA risk before initiating therapy. 1, 2
• Serial MRIs prior to the 2nd and 3rd infusions were not provided, despite guidelines requiring surveillance MRIs before the 2nd, 3rd, 4th, and 7th infusions. 1, 2
• Registry enrollment status (e.g., ALZ-NET) was not confirmed, which is required by the Aetna clinical policy bulletin. 1

Alternative Evidence-Based Treatment Approach

Appropriate First-Line Therapy:

• For this patient with early Alzheimer's disease (MMSE 27/30), the appropriate first-line treatment would be a cholinesterase inhibitor, specifically donepezil 5mg once daily, with consideration for dose escalation to 10mg daily after 4-6 weeks if well-tolerated. 5
• Donepezil is preferred due to once-daily dosing, absence of hepatotoxicity, and favorable side effect profile. 5
• The patient is already receiving donepezil 10mg and memantine 5mg, which represents guideline-concordant symptomatic therapy. 5

Vascular Risk Factor Management:

• Given the stroke history and documented cerebrovascular disease, aggressive management of vascular risk factors is paramount and may provide greater benefit than anti-amyloid therapy in this specific patient. 6
• Canadian stroke guidelines recommend intensive blood pressure control (SBP <120 mmHg) in patients over 50 to reduce mortality, cardio/cerebrovascular risk, and dementia/cognitive impairment. 6

Safety Concerns Specific to This Case

Elevated ARIA Risk Profile:

• The patient has documented hemorrhagic foci and prior cortical infarcts, which substantially increase the risk of symptomatic ARIA. 1, 2
• In the TRAILBLAZER-ALZ 2 trial, ARIA-edema/effusion occurred in 24% of donanemab-treated patients (52 symptomatic cases), with three treatment-related deaths. 4
• Concurrent aspirin use (81mg daily documented) further increases bleeding risk, though monotherapy antiplatelet use is permitted. 2

Modest Clinical Benefit vs. High Risk:

• Even in appropriate candidates, donanemab showed modest benefits: iADRS difference of 3.25 points and CDR-SB difference of -0.67 points at 76 weeks in the low/medium tau population. 1, 4
• The benefit profile is comparable to established symptomatic agents but carries substantially higher risks and costs. 1

Billing and Coding Issues

Incorrect CPT Code:

• CPT code 96413 (chemotherapy administration) is inappropriate for donanemab infusions. 1
• The appropriate coding for monoclonal antibody infusions would typically fall under therapeutic/diagnostic infusion codes, not chemotherapy administration. 1

Recommendation

These three doses of Kisunla were not medically necessary and should not have been administered given the documented stroke history, incorrect dosing protocol, and missing safety documentation. The patient should continue evidence-based symptomatic therapy with cholinesterase inhibitors and memantine, along with aggressive vascular risk factor management. 6, 5