Is continuation of Vyepti (eptinezumab-jjmr) 300 mg IV every 12 weeks medically necessary for preventive treatment of migraines?

Medical Necessity Assessment: Vyepti Continuation

Continuation of Vyepti 300 mg IV every 12 weeks is NOT medically necessary for this patient because she has failed to demonstrate the required reduction in migraine frequency and has reported worsening headache intensity, which directly contradicts the established efficacy criteria for continuation therapy. 1

Critical Failure to Meet Continuation Criteria

The patient explicitly fails to meet the standard continuation requirements:

• Aetna's medical necessity criteria require at least 3 months of treatment WITH demonstrated reduction in migraine days per month from baseline 1
• This patient reports daily headaches and states they have been "intense the last several months" - indicating worsening rather than improvement
• She has received adequate treatment duration (started 2/23/24, last infusion 8/22/25 = >18 months of therapy) but lacks the required therapeutic response 1

Evidence-Based Treatment Response Expectations

Eptinezumab typically demonstrates efficacy within the first month of treatment, with sustained response through subsequent dosing intervals:

• Clinical trials show that responders to eptinezumab demonstrate reduction in monthly migraine days as early as Day 1, with consistent efficacy maintained through 24 weeks 2, 3
• In the PROMISE-2 study, 54.5-60.6% of eptinezumab-treated patients achieved ≥50% migraine response during Month 1 4
• Patients who achieve early response (Month 1) have high likelihood of sustained response, with more than two-thirds maintaining ≥75% response for ≥3 months 4
• This patient's lack of improvement after >18 months strongly suggests treatment failure 1

Standard of Care Position for Eptinezumab

Eptinezumab is classified as third-line preventive therapy, reserved for patients who have failed first-line and second-line options:

• Current guidelines position eptinezumab as third-line treatment after failure of beta-blockers, topiramate, candesartan (first-line), and amitriptyline, flunarizine (second-line) 5
• The medication is FDA-approved for migraine prevention at 100 mg or 300 mg IV every 3 months, with some patients benefiting from the higher dose 2
• However, approval and dosing recommendations assume therapeutic response is achieved 2

Alternative Treatment Considerations

Given treatment failure with Vyepti, the following alternatives should be pursued:

• Other CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) may provide benefit, as failure of one preventive treatment does not predict failure of other drug classes 5, 1
• OnabotulinumtoxinA is indicated for chronic migraine (≥15 headache days/month) and should be strongly considered given this patient's daily headaches 5
• Re-trial of first-line agents with proper titration: The patient discontinued Topamax due to worsening, but other first-line options (beta-blockers, candesartan) are not documented as having been tried 5

Medication Overuse Consideration

The clinical picture raises concern for medication overuse headache, which can reduce effectiveness of preventive treatments:

• Daily headaches with multiple failed abortive medications (sumatriptan-naproxen, Maxalt, Nurtec, Ubrelvy) suggest possible medication overuse 5, 1
• Medication overuse can worsen the underlying migraine condition and reduce effectiveness of preventive treatments 1
• Continuation of an ineffective preventive medication while medication overuse persists is not medically sound 1

Clinical Trial Evidence Contradicts Continuation

The pivotal trials that established Vyepti's efficacy demonstrate clear response patterns that this patient lacks:

• PROMISE-1 (episodic migraine): Mean reduction of 3.9-4.3 migraine days/month vs 3.2 for placebo, with 49.8-56.3% achieving ≥50% response 2
• PROMISE-2 (chronic migraine): Demonstrated consistent reduction in migraine days with early onset of benefit 6, 4
• This patient's reported daily headaches with increased intensity represents treatment failure by any clinical trial metric 2, 4

Recommendation Summary

The treatment plan is NOT medically necessary because:

1. Patient fails to meet continuation criteria (no reduction in migraine days, worsening intensity) 1
2. Adequate trial duration has been provided (>18 months) without therapeutic benefit 1
3. Alternative evidence-based treatments remain available (other CGRP antibodies, onabotulinumtoxinA) 5, 1
4. Possible medication overuse headache requires different management approach 1

The treatment plan IS standard of care for migraine prevention in appropriate patients, but this specific patient has demonstrated clear treatment failure. 5, 2 Continuation would not be experimental, but rather medically inappropriate given lack of efficacy. 1