Is escalation to 300mg of Vyepti (Eptinezumab-jjmr) indicated for a patient currently on 100mg, with a regimen including Topiramate, Botox, Toradol (Ketorolac), Zavzpret (Zolmitriptan), and Nurtec (Rimegepant)?

Vyepti Dose Escalation Not Indicated at This Time

The patient should complete a full 3-month trial at 100mg before considering escalation to 300mg, and must demonstrate at least a 30% reduction in monthly migraine days from baseline to justify dose escalation. 1 Additionally, the concerning polypharmacy regimen with multiple acute medications (Toradol, Zavzpret, Nurtec) alongside preventive therapies (topiramate, Botox) raises significant concern for medication-overuse headache, which must be addressed before increasing Vyepti dosing. 1

Required Treatment Response Assessment

The patient needs documented baseline migraine frequency and a comparison after the 3-month trial at 100mg to determine if dose escalation is warranted. 1 The evidence shows:

• Eptinezumab demonstrates efficacy from day 1 after infusion, with primary endpoints measured at 12 weeks, and responder rates typically increase after the second infusion 1
• Clinical guidelines require at least 3 months of treatment with demonstrated reduction in migraine days per month from baseline before continuation or escalation is considered medically necessary 1
• The standard response threshold is ≥30% reduction in monthly migraine days 1

Medication Overuse Headache Concerns

The current regimen strongly suggests medication-overuse headache, which reduces the effectiveness of all preventive treatments including Vyepti. 1 Specific concerns include:

• Concurrent use of topiramate (preventive), Botox (preventive), and multiple acute medications (Toradol, Zavzpret, Nurtec) creates a complex polypharmacy situation 1
• Medication-overuse headache is defined as headache on ≥15 days/month with regular overuse of acute medications for >3 months 1
• This condition can worsen the underlying migraine and reduce effectiveness of preventive treatments, making dose escalation futile until addressed 1

Appropriate Dosing Protocol

The FDA-approved dosing schedule for eptinezumab is 100mg IV every 3 months, with escalation to 300mg IV every 3 months only for patients who may benefit from higher dosing after demonstrating response. 1 The clinical trial data supporting this approach:

• In the DELIVER trial of patients with 2-4 previous preventive treatment failures, eptinezumab 100mg reduced monthly migraine days by -4.8 days versus -2.1 for placebo over weeks 1-12 2, 3
• Eptinezumab 300mg reduced monthly migraine days by -5.3 days versus -2.1 for placebo 2, 3
• The difference between 100mg and 300mg doses was modest (0.5 days), suggesting 100mg provides substantial benefit 2, 3

Clinical Algorithm for This Patient

Before approving 300mg escalation, the following must occur:

1. Complete the 3-month trial at 100mg with documented baseline migraine frequency and post-treatment frequency 1
2. Demonstrate ≥30% reduction in monthly migraine days from baseline to justify any continuation or escalation 1
3. Address medication overuse by transitioning acute medications and potentially reducing the number of concurrent preventive therapies 1
4. Re-evaluate after addressing overuse to determine if the patient is a true non-responder to 100mg or if medication overuse was masking Vyepti's effectiveness 1

Guideline Positioning

Current guidelines position eptinezumab as third-line treatment after failure of first-line options (beta-blockers, topiramate, candesartan) and second-line options (amitriptyline). 1 The 2023 VA/DoD Clinical Practice Guideline provides only a "weak for" recommendation for intravenous eptinezumab for prevention of episodic or chronic migraine, noting it requires healthcare infrastructure for IV administration and patient time commitment. 4

Common Pitfall to Avoid

Do not escalate to 300mg without documented treatment response at 100mg. Failure of one preventive treatment does not predict failure of other drug classes, and patient-reported outcomes are critical in evaluating migraine therapy effectiveness. 1 Escalating dose prematurely in the setting of medication overuse will likely result in continued poor response and unnecessary cost escalation (annual costs of CGRP-mAbs range from $7,071-$22,790). 4, 5