Is Vyepti (Eptinezumab) 100mg IV infusion every 3 months medically necessary for chronic migraines?

Medical Necessity of Vyepti (Eptinezumab) 100mg IV Every 3 Months for Chronic Migraine

Yes, Vyepti 100mg IV infusion every 3 months is medically necessary for this patient with chronic migraine (G43.719) who has failed multiple prior preventive therapies and continues to experience inadequate control with current treatment. 1

Rationale for Medical Necessity

Diagnosis Confirmation

This patient meets ICHD-3 criteria for chronic migraine with ≥15 headache days per month for >3 months, with increased frequency despite current treatment. 2

Extensive Treatment Failure History

The patient has documented failures of:

• First-line oral preventives: propranolol (β-blocker), topiramate (anticonvulsant), amitriptyline (tricyclic antidepressant), duloxetine and venlafaxine would be alternatives (SNRI) 2
• Second-line therapy: Botox (onabotulinumtoxinA) for chronic migraine 2
• Third-line CGRP-targeted therapy: erenumab (CGRP receptor mAb), fremanezumab (Ajovy - CGRP mAb causing nausea), atogepant (oral CGRP antagonist) 2
• Multiple acute medications: 3 triptans, rimegepant (Nurtec), ubrelvy, diclofenac (Cambia) 2

Guideline Support for Eptinezumab

• The 2023 VA/DoD Clinical Practice Guideline provides a "weak for" recommendation for intravenous eptinezumab for prevention of both episodic and chronic migraine 3
• The 2021 Nature Reviews Neurology guideline lists eptinezumab as third-line preventive medication at 100 or 300 mg IV quarterly 2
• The 2025 American College of Physicians guideline acknowledges CGRP-mAbs (including eptinezumab) as evidence-based options after failure of less costly alternatives 2

Clinical Appropriateness in This Case

Sequential therapy requirement met: The patient has exhausted recommended first-line (β-blockers, anticonvulsants, tricyclic antidepressants) and second-line options (Botox), making third-line CGRP-targeted therapy appropriate. 2

Failure of alternative CGRP therapy: The patient failed fremanezumab (Ajovy) due to inadequate efficacy and nausea, and failed atogepant. Switching to a different CGRP-targeted agent (eptinezumab) is reasonable as failure of one does not predict failure of others. 2

Advantages of eptinezumab over current regimen:

• IV administration every 3 months may improve adherence compared to monthly subcutaneous injections (Ajovy) that caused nausea 2
• Eptinezumab demonstrates efficacy from day 1 after infusion in clinical trials 1, 4
• Effective in patients with medication-overuse headache (relevant given Norco use and rebound risk) 5
• Sustained or improved response rates through 24 weeks, with 65.9-70.4% achieving ≥30% reduction in monthly migraine days at 100mg dose 6

FDA-Approved Indication and Dosing

Eptinezumab is FDA-approved for preventive treatment of migraine in adults at 100mg IV every 3 months, with some patients benefiting from 300mg. 1 The requested 100mg dose is the standard starting dose. 1

Safety Profile

• Generally well-tolerated with most common adverse events being nasopharyngitis, upper respiratory infections, and sinusitis (mild) 7
• Hypersensitivity reactions can occur (2.1% in trials) but are manageable; contraindicated only in those with serious hypersensitivity to eptinezumab 1
• No significant drug interactions as it is not metabolized by cytochrome P450 enzymes 1

Critical Medication-Overuse Headache Consideration

Important caveat: The patient's use of Norco (opioid) carries rebound risk. 2 ICHD-3 defines medication-overuse headache as headache ≥15 days/month with regular overuse of acute medications for >3 months (any acute medication on ≥10 days/month). 2 While eptinezumab is effective in patients with medication-overuse headache 5, concurrent management of acute medication overuse is essential. The provider's plan to transition to ubrelvy (gepant with lower rebound risk than opioids) is appropriate. 2

Cost Considerations in Context

The 2025 ACP guideline notes annual costs of CGRP-mAbs range from $7,071-$22,790 versus substantially lower costs for first-line oral preventives ($67-$393 annually). 2 However, the guideline prioritizes less costly treatments as initial therapy when efficacy is similar. 2 This patient has already failed multiple less costly alternatives, making the higher cost of eptinezumab justified by medical necessity. 2, 3 The cost must be weighed against improved quality of life and reduced disability from effective migraine prevention. 3

Recommendation Summary

Vyepti 100mg IV every 3 months is medically necessary given documented chronic migraine with inadequate response to extensive prior therapies including first-line, second-line, and alternative third-line CGRP-targeted agents. 2, 3, 1 The patient meets FDA-approved indication, has appropriate treatment sequencing, and requires escalation to alternative CGRP therapy after Ajovy failure. 1

Concurrent requirement: Address medication-overuse headache risk by limiting opioid use and transitioning to gepants for acute treatment as planned. 2, 5