Is continuation of Vyepti (eptinezumab-jjmr) 300 mg IV every 12 weeks medically necessary for migraine prevention in a patient with increased headache frequency and intensity?

Medical Necessity Assessment for Vyepti Continuation

Continuation of Vyepti is NOT medically necessary in this case because the patient has experienced worsening symptoms rather than the required reduction in migraine days, failing to meet established efficacy criteria for continuation therapy. 1

Question 1: Medical Necessity Analysis

Failure to Meet Continuation Criteria

The patient does not meet the established threshold for continuation therapy. Aetna's medical necessity criteria explicitly require that patients demonstrate a reduction in migraine days per month from baseline after at least 3 months of treatment 1. This patient reports:

• Daily headaches (indicating approximately 30 headache days per month)
• Headaches described as "intense the last several months"
• Worsening symptoms rather than improvement 1

This represents treatment failure, not treatment success requiring continuation.

Clinical Evidence of Non-Response

The patient's clinical course demonstrates clear lack of efficacy:

• Despite receiving Vyepti 300 mg IV every 12 weeks since February 2024 (nearly 18 months of treatment), she reports daily headaches with increased intensity 1
• The VA/DoD Clinical Practice Guideline recommends trying alternative treatment when preventive therapy is ineffective after an adequate trial period 1
• Failure of one preventive treatment does not predict failure of other drug classes, making alternative therapies appropriate 1

Medication Overuse Headache Consideration

A critical pitfall in this case is the potential for medication overuse headache (MOH), which can reduce effectiveness of preventive treatments. 1 The patient's daily headaches combined with multiple failed abortive medications (sumatriptan-naproxen, Maxalt, Nurtec, Ubrelvy, NSAIDs, Frovatriptan) suggests possible medication overuse that may be confounding the clinical picture 1.

Question 2: Standard of Care Assessment

Current Position in Treatment Algorithm

Eptinezumab is considered third-line treatment after failure of first-line agents (beta-blockers, topiramate, candesartan) and second-line agents (amitriptyline, flunarizine). 1 Notably, this patient's documented trials show:

• Missing first-line trials: No documented trial of beta-blockers or candesartan 1
• Topamax was discontinued due to worsening, but proper titration and adequate trial duration are not documented 1
• The VA/DoD guideline gives eptinezumab only a "weak for" recommendation, noting it requires healthcare infrastructure for IV administration and significant patient time commitment 1

Alternative Evidence-Based Options

Given treatment failure with Vyepti, the following alternatives represent standard of care:

• OnabotulinumtoxinA (Botox) should be strongly reconsidered for chronic migraine (≥15 headache days/month), despite the patient's prior report of "worse pain" - proper injection technique and adequate trial duration are critical 1. This patient's daily headaches clearly meet chronic migraine criteria.

• Other CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) may provide benefit, as failure of one CGRP antagonist does not predict failure of others 1

• Re-trial of first-line agents: Beta-blockers and candesartan have not been documented as tried and should be considered before continuing a failed third-line therapy 1

Safety Profile

Eptinezumab has demonstrated acceptable safety in clinical trials, with treatment-emergent adverse events occurring at low frequency (nasopharyngitis, upper respiratory tract infections, sinusitis) 2. However, safety alone does not establish medical necessity when efficacy is absent.

Research Evidence Context

While the PROMISE-1 study showed sustained migraine-preventive effects through 1 year with reductions of 4.3-5.3 migraine days per month for the 300 mg dose 3, and the DELIVER trial demonstrated efficacy in patients with 2-4 previous preventive treatment failures 4, these trial results do not apply to individual patients who demonstrate treatment failure. The real-world EMBRACE II study showed 69% achieved ≥50% response rates 5, meaning 31% did not respond adequately - this patient appears to fall in the non-responder category.

Clinical Recommendation

The treatment plan should be changed, not continued. The appropriate next steps include:

1. Discontinue Vyepti due to lack of efficacy after 18 months of treatment 1
2. Evaluate and address potential medication overuse headache before initiating new preventive therapy 1
3. Consider onabotulinumtoxinA given daily headaches meeting chronic migraine criteria 1
4. Trial documented first-line agents (beta-blockers, candesartan) that have not been adequately attempted 1
5. Consider alternative CGRP monoclonal antibodies if first-line options fail 1

This represents experimental continuation of failed therapy rather than evidence-based standard of care.