Is eptinezumab (Vyepti) medically necessary for a patient with multiple sclerosis?

Eptinezumab (Vyepti) Was NOT Medically Necessary for Multiple Sclerosis

Eptinezumab is FDA-approved exclusively for migraine prevention in adults and has no established role in treating multiple sclerosis—the diagnosis code G35 (Multiple Sclerosis) represents an off-label, non-evidence-based use that does not meet medical necessity criteria.

Critical Distinction: Migraine vs. Multiple Sclerosis

The clinical documentation reveals this patient has two separate diagnoses:

• G35 (Multiple Sclerosis) - well-controlled on disease-modifying therapy
• Intractable chronic migraine without aura - the actual indication for eptinezumab 1, 2

The confusion arises because both conditions coexist in this patient, but eptinezumab treats only the migraine component 1, 2, 3.

Evidence-Based Indications for Eptinezumab

FDA-Approved Use

• Eptinezumab is indicated solely for preventive treatment of migraine in adults, administered as 100 mg or 300 mg intravenous infusion every 3 months 1, 2, 3
• Clinical trials (PROMISE-1, PROMISE-2, DELIVER) enrolled patients with episodic or chronic migraine, demonstrating significant reductions in monthly migraine days (4.8-5.3 day reduction vs. 2.1 days with placebo) 1, 4, 5
• The DELIVER trial specifically studied patients with 2-4 previous preventive treatment failures, showing efficacy in this difficult-to-treat population 1, 4

Multiple Sclerosis Treatment

• No evidence exists supporting eptinezumab for multiple sclerosis treatment in any guideline or research literature provided [6-7]
• MS disease-modifying therapies include natalizumab, ocrelizumab, alemtuzumab, fingolimod, and others—none of which include anti-CGRP antibodies 6, 8, 9
• MS treatment focuses on immune modulation and preventing demyelinating attacks, mechanisms entirely distinct from CGRP pathway inhibition 6, 8

Clinical Documentation Analysis

Appropriate Indication Present

The patient's chart clearly documents:

• "Intractable chronic migraine without aura" as the primary headache diagnosis
• Headache history since second grade with exacerbation after MS diagnosis and steroid treatment
• Multiple failed preventive therapies (zonisamide, Botox, occipital nerve blocks, trigger point injections)
• Continuation criteria met: >3 months treatment with reduction in migraine days 1, 4

Billing Code Error

The claim was submitted with diagnosis code G35 (Multiple Sclerosis) instead of the appropriate migraine diagnosis codes (G43.x series for migraine). This represents a coding error, not an inappropriate medication choice 1, 2.

Medical Necessity Determination

For Migraine Prevention (Correct Indication)

Eptinezumab 300 mg every 3 months IS medically necessary when billed with appropriate migraine diagnosis codes because:

• Patient has documented intractable chronic migraine with multiple preventive treatment failures 1, 4
• Dosing (300 mg IV every 90 days) matches FDA-approved regimen 1, 2, 3
• Patient has received >3 months treatment with clinical benefit (continuation criteria met) 1, 4
• Treatment is well-tolerated with acceptable safety profile 1, 2, 3

For Multiple Sclerosis (Incorrect Indication)

Eptinezumab is NOT medically necessary when billed with diagnosis code G35 because:

• No evidence supports eptinezumab for MS treatment [6-7]
• MS is well-controlled on current therapy (no new lesions, stable disease)
• Anti-CGRP antibodies have no mechanism of action relevant to demyelinating disease 6, 8

Recommendation for Claims Processing

Deny the claim as submitted with diagnosis code G35, but allow resubmission with appropriate migraine diagnosis codes (G43.709 for chronic migraine without aura, or G43.919 for intractable migraine) 1, 2.

Rationale

• The medication was appropriately prescribed and administered for migraine prevention 1, 4
• The patient meets all clinical criteria for eptinezumab continuation 1, 4, 5
• Only the diagnosis code on the claim is incorrect—this is a billing/coding error, not inappropriate prescribing 1, 2

Documentation Requirements for Approval

• Confirm diagnosis of chronic migraine (≥15 headache days/month with ≥8 migraine days/month) 1, 4
• Document 2-4 previous preventive treatment failures (met: zonisamide, Botox, nerve blocks) 1, 4
• Verify reduction in migraine days from baseline after ≥3 months treatment 1, 4
• Confirm appropriate dosing (100-300 mg IV every 3 months) 1, 2, 3

Common Pitfall to Avoid

Do not conflate comorbid conditions when determining medical necessity. This patient has both MS and migraine—two separate diseases requiring different treatments 6, 8, 1. The presence of MS does not invalidate the migraine diagnosis or the appropriateness of migraine-specific therapy 1, 4. The claim should be adjudicated based on the actual therapeutic target (migraine), not an unrelated comorbidity (MS) 1, 2.