Donanemab (Kisunla) is NOT Indicated for Multiple Sclerosis and Cannot Be Certified
Donanemab (Kisunla) is FDA-approved exclusively for early symptomatic Alzheimer's disease and has no approved or evidence-based use in multiple sclerosis—certification for MS treatment is inappropriate and should be denied. 1, 2
FDA-Approved Indication
Donanemab received traditional FDA approval on July 2,2024, specifically for adults with early symptomatic Alzheimer's disease (mild cognitive impairment or mild dementia stage), not for any neurological condition involving demyelination or immune-mediated CNS inflammation 1
The drug is an amyloid β-directed plaque-lowering monoclonal antibody that targets N-terminal pyroglutamate-modified forms of amyloid-β, a pathological mechanism entirely distinct from multiple sclerosis pathophysiology 2, 3
Mechanism of Action Incompatibility
Donanemab works by clearing amyloid plaques in Alzheimer's disease, whereas MS is an inflammatory demyelinating disease requiring immunomodulation or B-cell depletion 1, 2
The patient is already appropriately treated with Kesimpta (ofatumumab), a fully human anti-CD20 monoclonal antibody specifically approved for relapsing forms of MS that depletes B-cells to reduce inflammatory activity 4, 5
There is no mechanistic rationale for adding an anti-amyloid antibody to a patient with MS who is already on appropriate disease-modifying therapy 1, 4
Appropriate MS Treatment Pathway
For this patient with MS already on Kesimpta:
Continue Kesimpta as prescribed, which has demonstrated efficacy in reducing annualized relapse rates, MRI-detected lesion activity, and disability worsening in relapsing MS 4
Monitor with brain MRI at least annually using contrast-enhanced T1-weighted and T2-weighted sequences to assess disease activity 1
If the patient shows breakthrough disease activity on Kesimpta (new relapses or MRI lesions), consider switching to alternative high-efficacy DMTs such as alemtuzumab, ocrelizumab, or natalizumab 1
For patients requiring enhanced monitoring due to immunosuppression, brain MRI should be performed every 3-4 months 1
Critical Safety Concerns
Donanemab carries specific risks including Amyloid-Related Imaging Abnormalities (ARIA-E in 12.6% and ARIA-H in 15-20% of patients), which require specialized monitoring protocols entirely irrelevant to MS management 6, 3
The drug requires pre-treatment MRI screening for exclusionary findings (multiple lacunar infarcts, macrohemorrhages, microhemorrhages, superficial siderosis) that are specific to cerebrovascular risk assessment in Alzheimer's patients, not MS patients 6
Combining donanemab with Kesimpta would expose the patient to dual immunosuppression without any evidence of benefit and potential for additive adverse effects 4, 3
Documentation for Denial
The certification should be denied with the following justification:
J0175 (donanemab/Kisunla) is FDA-approved only for Alzheimer's disease, not multiple sclerosis 1, 2
The patient has a diagnosis of MS, not Alzheimer's disease or cognitive impairment meeting Alzheimer's criteria 1
The patient is appropriately treated with Kesimpta (ofatumumab), an FDA-approved MS therapy 4, 5
No published evidence, clinical trials, or guidelines support off-label use of donanemab in MS 1, 2
The mechanism of action (anti-amyloid antibody) is irrelevant to MS pathophysiology (inflammatory demyelination) 2, 3