Is continuation of Vyepti (eptinezumab) 300 mg IV every 3 months medically necessary for a patient with chronic migraines who has shown no improvement in migraine frequency?

Continuation of Vyepti is NOT Medically Necessary in This Case

Based on the insurance company's medical necessity criteria and established treatment guidelines, continuation of Vyepti (eptinezumab) 300 mg IV every 3 months is NOT medically indicated for this patient because she has demonstrated no improvement in migraine frequency after at least 3 months of treatment. 1

Medical Necessity Criteria Not Met

The insurance company's policy explicitly states that continuation of eptinezumab requires:

• At least 3 months of treatment with the requested medication AND
• A reduction in migraine days per month from baseline 1

This patient fails to meet the second criterion. She continues to have daily migraine headaches without any improvement on Vyepti, despite receiving it for at least 3 months (every three months dosing schedule). 1

Standard of Care Supports Discontinuation

Treatment Response Timeline

• The VA/DoD Clinical Practice Guideline (2024) recommends trying an alternative treatment when preventive therapy is ineffective after an adequate trial period 2, 1
• Clinical trial data demonstrates that eptinezumab efficacy is typically evident within the first 3 months of treatment, with primary endpoints measured at 12 weeks 3
• While some initial non-responders may respond after a second infusion (30.4% in the DELIVER trial), this patient has already received multiple doses without benefit 1

Evidence-Based Treatment Failure Definition

• The FDA-approved pivotal trials (PROMISE-2) defined treatment success as reduction in monthly migraine days from baseline 3
• In the chronic migraine trial, eptinezumab 300 mg reduced migraine days by 8.2 days per month compared to 5.6 days with placebo 3
• This patient reports daily headaches with no improvement, indicating complete treatment failure 1

Clinical Reasoning for Discontinuation

Medication Overuse Headache Consideration

This patient presents with concerning features suggesting medication overuse headache (MOH):

• Daily migraine headaches 2
• Taking Nurtec every other day (15 days/month) 2
• Multiple acute medications (Nurtec, Diamox, Trazodone) 2
• MOH is defined as headache on ≥15 days/month with regular overuse of acute medications for >3 months 2

Medication overuse can worsen underlying migraine and reduce effectiveness of preventive treatments 2, 1. This may explain the lack of response to both Botox and Vyepti.

Alternative Treatment Options Should Be Pursued

The patient has been appropriately referred to a headache clinic, where the following should be considered:

First-line preventive options not yet documented as tried:

• Beta-blockers 2
• Topiramate (discontinued previously but may warrant re-trial with proper titration) 2
• Candesartan 1

Other CGRP monoclonal antibodies:

• Failure of one preventive treatment does not predict failure of other drug classes 1
• Alternative CGRP antagonists (erenumab, fremanezumab, galcanezumab) may provide benefit 1

OnabotulinumtoxinA optimization:

• The patient is already receiving Botox, which is FDA-approved for chronic migraine 2
• However, she reports no improvement, suggesting either inadequate dosing, improper injection technique, or true treatment failure 2

Multimodal Approach Required

Chronic migraine generally requires a multimodal and multidisciplinary approach 2:

• Address medication overuse headache first 2
• Identify and reduce aggravating factors/triggers 2
• Consider non-pharmacologic treatments (cognitive-behavioral therapy, biofeedback) 2
• Treat comorbid conditions (sleep disturbance - she only gets 4-5 hours/night) 2

Answers to Specific Questions

1. Is the treatment plan medically necessary for the condition being treated?

No. Continuation of Vyepti is not medically necessary because:

• The patient has failed to demonstrate any reduction in migraine frequency after an adequate trial period 1
• Insurance medical necessity criteria require documented improvement, which is absent 1
• Continuing an ineffective preventive medication delays transition to potentially effective alternatives 2, 1
• The patient likely has medication overuse headache, which must be addressed before preventive therapy can be optimized 2

2. Is the treatment plan considered standard of care or experimental/investigational?

Eptinezumab is FDA-approved and considered standard of care for migraine prevention 2, 3. However, continuing an ineffective treatment contradicts standard of care principles:

• The VA/DoD guideline gave eptinezumab only a "weak for" recommendation, noting it requires healthcare infrastructure and patient time commitment 2
• Standard of care dictates discontinuing ineffective preventive therapy after an adequate trial 2, 1
• Guidelines emphasize that failure of one preventive does not predict failure of others, supporting transition to alternative therapy 1

Common Pitfalls to Avoid

Do not continue ineffective preventive therapy indefinitely - This delays appropriate treatment and wastes healthcare resources 2, 1

Do not overlook medication overuse headache - This patient's daily Nurtec use (every other day = 15 days/month) meets MOH criteria and must be addressed 2

Do not assume all CGRP antagonists will fail - Failure of eptinezumab does not predict failure of other CGRP monoclonal antibodies or gepants 1

Do not neglect non-pharmacologic interventions - Behavioral medicine, sleep optimization, and trigger management are essential components of chronic migraine care 2

Recommendation

Discontinue Vyepti and transition to alternative preventive therapy under the guidance of the headache clinic. The headache specialist should:

1. Address medication overuse headache by reducing acute medication frequency 2
2. Optimize or discontinue Botox if truly ineffective 2
3. Consider alternative CGRP monoclonal antibodies or first-line oral preventives not yet tried 1
4. Implement non-pharmacologic interventions 2
5. Address sleep disturbance (currently only 4-5 hours/night) 2